Clinical Update - Debio 025 in Hepatitis C

Debiopharm Group (Debiopharm), a global biopharmaceutical development specialist that focuses on serious medical conditions, particularly in the field of oncology, presented results from a phase IIa study with Debio 025, a selective cyclophilin (Cyp) inhibitor with a potent anti-hepatitis C (HCV) effect. Revealed at the 44th Annual Meeting of the European Association for the Study of the Liver, in Copenhagen, these findings showed potent antiviral activity.

 

The phase IIa study investigated the efficacy and safety of Debio 025 in combination with Peg interferon alpha 2a (peg-IFNÿ±2a) and ribavirin in previously null-responder genotype 1 HCV patients. Results demonstrated that Debio 025 at doses of 400 mg (with initial loading) and 800 mg daily for 29 days shows a statistically significant reduction of HCV RNA of respectively -1.96 log (-98.9%) and -2.38 log (-99.5%) when co-administered with Peg-IFN alpha-2a and ribavirin in previous null responders.

 

"These results in patients who are highly unlikely to respond to re-treatment with an interferon-based regimen, are very important to us, as they confirm that Debio 025 is a potent anti-HCV agent," said Rolland-Yves Mauvernay, President and Founder of Debiopharm Group. "We are making it our mission to find a cure for this widely spread and life threatening disease and these findings bring us one step closer to our goal."

 

About the phase IIa triple therapy study

 

Debiopharm investigated different dosing regimens of Debio 025 in combination with peg-IFNÿ±2a at 180 micrograms/week and ribavirin at 1000/1200 mg/day in genotype 1 chronic HCV patients that were previously null responders (< 2 log10 HCV-RNA reduction after 12 weeks with peg-IFN(alpha) 2a and ribavirin). Fifty patients were randomised in an open phase IIa study to receive one of five treatment regimens for 29 days. Afterwards patients continued treatment on Peg-IFN alpha-2a and Ribavirin. A loading dose of Debio 025 at the start of treatment accelerates the onset of action and enhances efficacy in the early stage of treatment.

 

About Debio 025

 

Debio 025 is a synthetic first-in-class Cyp inhibitor, being tested in humans as a potential anti-HCV drug. Debio 025 binds strongly to Cyp, host cell proteins thought to confer a replication advantage to HCV. Its potent inhibitory activity on the HCV replication was shown in the following clinical studies. Results of a phase Ib study demonstrate that Debio 025 monotherapy for 15 days induced a strong anti-HCV effect (3.6 log10 reduction) in HIV-1/HCV co-infected patients. (Hepatology, 47:817-26). Results of a phase IIa study with Debio 025 indicate that Debio 025 shows an important additive anti-HCV effect (4.6 log10 reduction) when co-administered with peg-IFN(alpha)2a to treatment-naive HCV patients. (Hepatology, in press)

 

About HCV

 

Globally, an estimated 170 million persons are chronically infected with HCV and 3 to 4 million are newly infected each year. HCV, in combination with hepatitis B, now accounts for 75% of all cases of liver disease around the world. HCV is considered by the World Health Organization as an epidemic. Because HCV can infect a patient for decades before being discovered, it is often called the "silent" epidemic. Studies suggest that in the US alone, nearly 4 million people are or have been infected with HCV and of these, 2.7 million have an ongoing chronic infection, the majority being between 40 to 60 years old.

 

About Debiopharm Group

 

Debiopharm Group is a global biopharmaceutical development specialist that in-licenses promising biological and small molecule drug candidates. It develops its products for global registration and maximum commercial potential. Once registered, the products are out-licensed to pharmaceutical partners for sales and marketing. Debiopharm independently funds the worldwide development of all of its products while providing expertise in pre-clinical and clinical trials, manufacturing, drug delivery and formulation, and regulatory affairs.

 

Founded in 1979 and headquartered in Lausanne, Switzerland, Debiopharm has developed three products with global combined sales in excess of $2.6 billion in 2008.

 

For more information on Debiopharm Group, please visit: http://www.debiopharm.com.

 

    Debiopharm S.A. Contact:
    Maurice Wagner,
    Director Corporate Affairs & Communications,
    Tel.: +41(0)21-321-01-11,
    Fax: +41(0)21-321-01-69,
    mwagner@debiopharm.com.

 

    Additional Media Contacts:

 

    In London,
    Maitland,
    Brian Hudspith,
    Tel: +44(0)20-7379-5151,
    bhudspith@maitland.co.uk.

 

    In New York,
    Russo Partners, LLC,
    Martina Schwarzkopf, Ph.D.,
    Account Executive,
    Tel: +1-212-845-4292,
    Fax: +1-212-845-4260,
    martina.schwarzkopf@russopartnersllc.com.

 

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Anti-ageing cosmetic reduced wrinkles in clinical trial

Scientists testing a cosmetic anti-ageing product sold on the high street have shown it can clinically reduce wrinkles and improve the appearance of skin damaged by everyday exposure to sunlight.

 

Dermatologists at The University of Manchester carried out a clinical trial on 60 volunteers with typical signs of sun-damaged skin and found that the cosmetic, No7 Protect & Perfect Intense Beauty Serum, could improve some of these clinical features.

 

The study, published online in the British Journal of Dermatology today (Tuesday, April 28), showed that 70% of individuals using the beauty product had significantly fewer wrinkles after 12 months of daily use compared to volunteers using a placebo.

 

The research team, headed by Professor of Dermatology Chris Griffiths, reported last year that the original No7 Protect & Perfect Beauty Serum stimulated the production of fibrillin-1, a protein that promotes elasticity in the skin.

 

For this latest, year-long study, the researchers first wanted to discover whether the new No7 Protect & Perfect Intense Beauty Serum also promoted fibrillin-1 production but also wished to test whether this would result in a reduction in wrinkles, as has been demonstrated with prescription retinoids.

 

"Very few over-the-counter cosmetic 'anti-ageing' products have been subjected to a rigorous, scientific trial to prove their effectiveness," said Professor Griffiths, who is based in the University's School of Translational Medicine at Salford Royal Foundation Hospital.

 

"Although prescription retinoids can have a reparative effect on photo-aged skin, there is scant evidence that any of the plethora of cosmetic 'anti-ageing' products can produce similar effects."

 

The clinical trial – funded by Boots, the makers of the No7 product range – was carried out using standard scientific protocols. Having established that the No7 Protect & Perfect Intense Beauty Serum did increase fibrillin-1 production, 60 volunteers – 11 men and 49 women aged 45 to 80 years – were recruited to test its efficacy.

 

The No7 Protect & Perfect Intense Beauty Serum and a control formulation containing no anti-ageing ingredients were supplied in identical, coded packages, so neither investigators nor volunteers were aware as to the treatment of each individual. Thirty volunteers were assigned the No7 Protect & Perfect Intense Beauty Serum and 30 used the placebo formulation.

 

"Our findings demonstrate that a commercially-available cosmetic can produce significant improvement in the appearance of facial wrinkles following long-term use," said Professor Griffiths.

 

"It is rare for such benefits to be reported for an over-the-counter anti-ageing product and this study paves the way for larger studies with more statistical power."

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Ridge Diagnostics wins Phase II National Science Foundation grant

Grant supports first blood test for depression

 

Ridge Diagnostics, a neurodiagnostic company commercializing a proprietary blood test for depression or major depressive disorder, has received a Phase II, National Science Foundation, Small Business Innovation Research program grant.

 

According to the company, the grant will be used to further the clinical development and commercialization of the company's blood test for depression, reported to be the first blood test for any neuropsychiatric disorder.

 

The test can be used in pharmaceutical research to objectively identify and stratify patient populations to enhance drug research and clinical studies, the company said. It is intended to be used by psychiatrists and primary care physicians to diagnose and monitor treatment of patients with depression.

 

Stan Sewitch, president and CEO of Ridge, said: "We are pleased to announce the National Science Foundation's recognition of Ridge's technological accomplishments. This grant will enable us to further the clinical development of our blood tests and build on our Clinical Laboratory Improvement Amendments laboratory infrastructure to support our growing business."

 

Ridge Diagnostics is a neurodiagnostic company commercializing a breakthrough, proprietary blood test for the diagnosis and treatment monitoring of Major Depressive Disorder (MDD). The company's products are derived from a proprietary Human Biomarker Library and Hyper‐MappingTM technology. Ridge intends to develop a comprehensive neuropsychiatric disease diagnostic franchise.

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BioMS Medical obtains positive review for Phase III multiple sclerosis trial

BioMS Medical has reported that the independent data safety monitoring board for the company's pivotal Phase III Maestro-01 Canadian/European trial of dirucotide in patients with secondary progressive multiple sclerosis has completed a safety analysis and recommended that the trial continue as per the protocol.

 

Maestro-01 is a multi-center, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of dirucotide in patients with secondary progressive multiple sclerosis. The study is being conducted at 47 sites across Canada and nine countries in Europe and includes 611 patients being administered either dirucotide or placebo intravenously every six months for a period of two years.

 

The primary clinical endpoint for the trial is defined as a statistically and clinically significant increase in the time to progression of the disease, as measured by the expanded disability status scale, in patients with HLA-DR2 and/or HLA-DR4 immune response genes. Time to disease progression in patients with other HLA-DR types will be assessed separately as an exploratory arm of the same study.

 

This was the final scheduled review by the data safety monitoring board (DSMB) prior to the completion of Maestro-01. The purpose of the DSMB is to provide objective, independent safety monitoring of the trial. Results from Maestro-01 are expected in the second half of 2009.

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Tranzyme Pharma reports positive results from Phase II gastroparesis trial

Tranzyme Pharma has reported that its potent and selective ghrelin agonist, TZP-101, demonstrated effectiveness in the treatment of gastroparesis, an inability of the stomach to empty food efficiently, especially in patients with diabetes mellitus.

 

Clinical trial results indicated that TZP-101 was safe and highly effective in improving multiple symptoms associated with gastroparesis, the company said. A total of 76 patients with either type 1 or type 2 diabetes mellitus and a confirmed diagnosis of gastroparesis were enrolled in a US and EU, double-blind, placebo-controlled Phase II trial designed to evaluate the safety and efficacy of TZP-101.

 

Patients were voluntarily admitted to the hospital and adaptively randomized to receive a daily 30-minute intravenous infusion of one of six doses of TZP-101 (20-600mcg/kg) or placebo for four consecutive days. Overall, 57 subjects received TZP-101 and 19 received placebo. Patient safety was monitored by vital signs, ECGs, physical exams, clinical chemistry and adverse events.

 

During treatment and at a 30-day follow-up visit, efficacy was evaluated by symptom improvement as assessed by both the patients and the investigators. The gastroparesis cardinal symptom index was administered to each subject prior to dosing, on each of the treatment days and at the follow-up visit. Additionally, meal-related gastroparesis symptom assessment and clinician rated symptom assessment (CRSA) scores were collected for the study.

 

The company said that 80mcg/kg was determined to be the TZP-101 dose which achieved maximum clinical benefit. Upon completion of the four-day dosing period, improvement in symptoms in TZP-101-treated subjects was statistically significant over placebo-treated subjects as determined by one or more of the evaluation tools for the following symptoms: vomiting (p=0.006), loss of appetite (p=0.034), postprandial fullness (p=0.007), early satiety (p=0.087), abdominal distension (p=0.053) and bloating (p=0.0822).

 

Statistical significance was also observed by the CRSA overall symptom scores (p=0.046). The 30-day follow-up evaluation demonstrated a sustained benefit in symptom improvement in the TZP-101 group. This effect reached statistical significance (p=0.023) for vomiting, a particularly debilitating complication of gastroparesis. In addition, proportionally fewer subjects (3%) in the TZP-101 group required hospitalization for gastroparesis during the 30-day follow-up period versus the placebo group (10%). TZP-101 was safe and well-tolerated at all doses tested.

 

Vipin Garg, president and CEO of Tranzyme, said: "We recognize the severity of symptoms caused by gastroparesis and their impact on quality of life, and are anxious to bring relief to the millions of patients suffering from this condition. We now plan to initiate a Phase III program to further evaluate the efficacy and safety of TZP-101 in this patient population."

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Schering-Plough reports encouraging results from Phase II hepatitis trial

Schering-Plough has reported that final results of the hepatitis C virus Sprint-1 study showed boceprevir, its investigational oral hepatitis C protease inhibitor, in combination with peginterferon alfa-2b and ribavirin, significantly increased sustained virologic response rates with 28 and 48 weeks of therapy compared to current standard of care, peginterferon and ribavirin for 48 weeks.

 

In part I of the study, a 48-week boceprevir regimen achieved a 75% sustained virologic response (SVR) rate (n=77/103) in patients who received four weeks of Pegintron and Rebetol (P/R) followed by the addition of boceprevir (800mg TID) for 44 weeks (boceprevir P/R lead-in regimen). This represents a near doubling of the 38% SVR rate (n=39/104) for patients in the control group (p<0.0001), the company said. In a 28-week boceprevir P/R lead-in regimen 56% of patients (n=58/103) achieved SVR (p=0.005).

 

Importantly, the likelihood of attaining SVR was greater for patients who received the boceprevir P/R lead-in regimens compared to the no lead-in arms. Of patients in the boceprevir P/R lead-in arms who achieved a rapid virologic response (RVR), 94% in the 48-week regimen and 82% in the 28-week regimen achieved SVR. RVR is defined as undetectable virus (HCV RNA) in plasma at four weeks after the addition of boceprevir. In the lead-in arms, 64% of patients achieved RVR. Fewer patients in the lead-in arms discontinued treatment due to viral breakthrough, the company said.

 

Part II of the hepatitis C virus (HCV) Sprint-1 study explored a low-dose ribavirin strategy in which boceprevir was given in combination with Pegintron and low-dose Rebetol for 48 weeks. SVR for the low-dose Rebetol arm was 36% (n=21/59) compared to 50% for a 48-week control arm with Pegintron and standard-dose Rebetol plus boceprevir (n=8/16).

 

In contrast to the results seen in part I, the low-dose Rebetol regimen was associated with increased viral breakthrough during treatment, higher relapse rates after the end of treatment and lower SVR, strongly indicating that standard-dose ribavirin is required to optimize response, the company noted.

 

Another key finding of the HCV Sprint-1 study is that treatment-emergent anemia appeared to be associated with higher SVR, with anemic patients (hemoglobin decreasing to less than 10g/dl) having higher SVR rates than those without anemia (hemoglobin did not decrease to less than 10g/dl).

 

Paul Kwo, lead investigator of the study, said: "These results are very exciting and provide important insights to help further define response guided therapy using a P/R lead-in boceprevir regimen with peginterferon and ribavirin backbone treatment. Building on these results, the boceprevir Phase III clinical program individualizes treatment based on response, utilizing RVR criteria at week four of boceprevir treatment to determine overall duration of therapy. Based on the RVR rate seen in this Phase II study, we are hopeful that the majority of patients can be treated with 28 weeks of therapy."

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MediciNova reports encouraging results from Phase II asthma trial

MediciNova and the Hercules Market of the Osaka Securities Exchange have reported final results from its Phase II clinical trial evaluating MN-221 at planned escalating doses of 240 to 1,080mcg in patients with severe, acute exacerbations of asthma treated in emergency departments.

 

The study included 29 patients with severe, acute exacerbations of asthma. All patients received standardized care consisting of inhaled albuterol, ipratropium and oral steroid treatment. No safety concerns with adding MN-221 to standardized care were identified following review of electrocardiogram (ECG), laboratory and adverse experience data, the company said.

 

The hospitalization rate among patients treated with standardized care only was 46% (six of 13), which was the anticipated rate, compared to a hospitalization rate of 25% (four of 16) among patients receiving MN-221 plus standardized care. This represents a 45% reduction in hospitalization rate among patients treated with MN-221. All hospitalizations were due to asthma exacerbations which were judged to be unrelated to study medication and therefore do not raise safety concerns for adding MN-221 to standardized care.

 

As specified in the protocol for this clinical trial, no inferential statistics (i.e., p-values) were calculated for this study. Improvement in forced expiratory volume in one second (FEV(1)) values generally appeared to be greater for patients receiving MN-221 in addition to standardized treatment.

 

MediciNova also announced that its MN-221-CL-007 study, a randomized, double-blind, placebo-controlled Phase II clinical trial designed to evaluate the safety and efficacy of MN-221 in patients with severe, acute exacerbations of asthma, has begun enrolling patients in the US. The majority of investigators who participated in the MN-221-CL-006 study have rolled over to the MN-221-CL-007 study.

 

MediciNova expects to enroll approximately 200 patients at approximately 35 emergency department clinical sites, including the clinical sites rolled over from the MN-221-CL-006 study, in North America, Australia and New Zealand. The MN-221-CL-007 study is designed to compare standardized care to standardized care plus MN-221 at a dose of 1.2mg administered over one hour.

 

Patients enrolled in the study will continue to receive standardized care as needed while receiving an intravenous infusion of MN-221 or placebo. The primary efficacy endpoint will be improvement in FEV(1). Enrollment of study participants began in April 2009 in the North American clinical sites and is anticipated to begin by June 2009 in the Australia and New Zealand clinical sites. Enrollment is expected to be complete within nine to 12 months.

 

Yuichi Iwaki, president and CEO of MediciNova, said: "These clinical results are consistent with the interim data reported from this study in January 2009 and demonstrate the potentially beneficial effect of MN-221 in the treatment of severe, acute exacerbations of asthma. The benign safety profile of MN-221 and the 45% reduction in hospitalization rate observed are encouraging."

 

 

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Phase 3 Trial of Nexavar in Chemotherapy-Naive Patients with Advanced Melanoma Does Not Meet Primary Endpoint

Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. (Nasdaq:  ONXX) today announced that a Phase 3 trial evaluating Nexavar(R) (sorafenib) tablets in patients with unresectable stage III or stage IV melanoma was stopped early following a planned interim analysis by the independent Data Monitoring Committee (DMC). The trial was sponsored by the National Cancer Institute (NCI) and led by the Eastern Cooperative Oncology Group (ECOG) under a Clinical Trials Agreement between NCI and Bayer and Onyx. The DMC concluded that the study would not meet the primary endpoint of improved overall survival among patients receiving Nexavar in combination with the chemotherapeutic agents carboplatin and paclitaxel versus patients receiving placebo plus the chemotherapeutic agents. The treatment effect was comparable in each arm. The DMC also reported that there were no unexpected serious side effects, though the final analysis of the data will occur per protocol and statistical analysis plan.

 

Bayer and Onyx will further review the findings of this analysis to determine what, if any, impact these data might have on other ongoing Nexavar melanoma trials. Data from this study are expected to be presented at an upcoming scientific meeting.

 

"We're disappointed with the results of the study and that the therapy did not bring benefit to patients with melanoma, a historically difficult tumor to treat," said Todd Yancey, M.D., vice president of clinical development at Onyx. "Onyx and Bayer remain committed to our broad clinical program to investigate the potential of Nexavar in a wide range of cancers, and we intend to build upon the success of Nexavar in our approved indications in hepatocellular carcinoma (liver cancer) and advanced renal cell carcinoma (kidney cancer)."

 

Phase 3 Trial Design

 

The multicenter, randomized, double-blind, placebo-controlled Phase 3 study enrolled patients with unresectable stage III or stage IV melanoma at more than 200 clinical sites in the United States and Australia. The primary efficacy endpoint was overall survival, and secondary endpoints included progression-free survival and response rate.

 

Patients were randomized to receive 400 mg oral Nexavar twice daily or placebo, in addition to two chemotherapeutic agents - carboplatin and paclitaxel. Following 10 cycles of Nexavar or placebo plus chemotherapy, patients who achieved a response to the combination continued in a maintenance phase where Nexavar or placebo was administered as a single agent until disease progression.

 

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Antisense Pharma Begins Pivotal Phase III Clinical Trial with Trabedersen in Aggressive Brain Tumors

First Patients Enrolled in International SAPPHIRE Study of Recurrent or Refractory Anaplastic Astrocytoma

The biopharmaceutical company Antisense Pharma GmbH has announced today that the first patients with recurrent or refractory anaplastic astrocytoma have been enrolled in the pivotal Phase III clinical trial SAPPHIRE. The SAPPHIRE study is a randomized, active-controlled, clinical trial designed to confirm the efficacy and safety of the investigational drug trabedersen , observed in the previous clinical studies. Trabedersen is being investigated as monotherapy compared to current standard therapy with temozolomide . The results of the previous randomized, active-controlled Phase IIb study show that the novel, targeted therapy holds much promise.

International Phase III study designThe SAPPHIRE study will be carried out in Europe, America and Asia. Approximately 70 hospital centers will participate. The Phase III study is designed as a randomized, active-controlled, open-label clinical trial with two treatment arms: Trabedersen in a dose of 10 µM will be compared to current standard therapy with either temozolomide or BCNU. Clinical centers conducting the SAPPHIRE study aim to enroll a total of approximately 130 adult patients with recurrent or refractory anaplastic astrocytoma. Trabedersen will be administered intratumorally via one single catheter using convection-enhanced delivery on an outpatient treatment basis. The treatment period lasts up to 6 months consisting of 7-day cycles every other week.

Study objectivesThe primary efficacy endpoint is the survival rate at 24 months. Further efficacy endpoints include overall survival and time to death. The 14-month progression rate is the surrogate endpoint for an interim analysis. Safety parameters will include adverse events, serious adverse events, ECG parameters, neurological examination and vital signs. Also the patient’s quality of life is an important parameter of the study.

Great need for new approaches in cancer therapy"The diagnosis of recurrent or refractory anaplastic astrocytoma is still devastating even today, since the therapeutic possibilities available to treat such patients are indeed quite inadequate. Most patients die within a few months after their diagnosis. Hospitals worldwide are committed to improve his situation in the framework of the SAPPHIRE study. The results of the previous studies show that the new, targeted therapy holds much promise, remarked Dr. Rolando Del Maestro, Director of Brain Tumor Research at the Montreal Neurological Institute and Hospital. Dr. Del Maestro is the coordinating investigator of the SAPPHIRE study.

Targeted therapies drive market growthTrabedersen is a first-in-class targeted therapy. This novel compound acts multimodally via inhibition of transforming growth factor-beta 2 . Unlike non-specific therapies, e. g. chemotherapy or radiotherapy, targeted therapies act much more specifically at the molecular roots of the disease. Commanding up to 80% of the growing oncology market, the targeted therapies like trabedersen substantially drive the growth of the pharmaceutical market . A successful marketing authorization would make trabedersen the first TGF-beta targeting drug for the treatment of cancer.

Combating cancer at its roots"We have taken trabedersen all the way from drug discovery to the pivotal Phase III clinical trial. The enrollment of the first patients in the SAPPHIRE study is a key milestone in our drug development program for trabedersen. It is also in Phase I/II clinical development for advanced pancreatic carcinoma, malignant melanoma and colorectal carcinoma. Trabedersen with its unique mode of action can lead to a paradigm shift towards tackling malignant tumors at their roots while providing a better quality of life for patients,” commented Dr. Karl-Hermann Schlingensiepen, Chief Executive Officer of Antisense Pharma.

For more information on the SAPPHIRE trial please visit the website www.anticancer.de.

Additional information

Original title Phase III SAPPHIRE studyEfficacy and Safety of AP 12009 in Adult Patients with Recurrent or Refractory Anaplastic Astrocytoma as Compared to Standard Treatment with Temozolomide or BCNU: A Randomized, Actively Controlled, Open-label Clinical Phase III Study. Principal Investigator: Professor Rolando Del Maestro, MD, PhD, Director Brain Tumour Research Centre, Montreal Neurological Institute and Hospital, Canada.

Trabedersen and TGF-beta 2Trabedersen is a first-in-class gene silencing antisense compound - a phosphorothioate oligodeoxynucleotide - designed to selectively downregulate the production of transforming growth factor-beta 2 at the translational level. TGF-ß2 plays a pivotal role as a multimodal cytokine by regulating key mechanisms of tumor progression. Immunosuppression, invasion and metastasis, proliferation and angiogenesis are simultaneously promoted by TGF-ß2 in a variety of malignant tumors. Trabedersen is a targeted multimodal therapy, therefore.

Results of the Phase IIb study with trabedersenThe completed clinical Phase IIb study AP 12009-G004 was an open-label, randomized, active-controlled, parallel-group dose finding study to evaluate the efficacy and safety of two doses of trabedersen in adult patients with recurrent or refractory high-grade glioma. At 29 international clinical centers, 134 evaluable patients were randomized to three arms: 10 µM trabedersen, 80 µM trabedersen or standard chemotherapy as active control. Analysis of the core phase revealed long-lasting tumor responses and life extension in AA and GBM patients, by far exceeding the active treatment period with trabedersen. For recurrent or refractory anaplastic astrocytoma patients, median survival times in the 10 µM trabedersen group were 39.1 months compared to 21.7 months in the standard chemotherapy control arm, translating to a survival benefit of 17.4 months for patients receiving the antisense treatment over standard chemotherapy. 83.3% of the patients with recurrent anaplastic astrocytoma who received 10 µM trabedersen survived two years or more, whereas only 41.7% survived two years in the control arm with standard chemotherapy. Both efficacy and safety results have demonstrated, that the 10 µM concentration of trabedersen was superior to the 80 µM concentration. This further underlines the specificity of this targeted therapy since for optimally targeted therapies maximum tolerated dose is not necessarily the most efficant dose.

High-Grade GliomaAnaplastic astrocytoma and glioblastoma multiforma are the two most common forms of primary brain tumors and are diseases with high unmet medical need. Adults as well as children may be affected, although the peak age is 45-65 years. Current therapies comprise surgery, radiation and/or chemotherapy. Despite recent advances, the prognosis for these patients is still poor, with a high proportion dying within two years after initial diagnosis. Antisense Pharma is the sponsor of the SAPPHIRE clinical Phase III study, investigating the efficacy and safety of trabedersen in adult patients with recurrent or refractory anaplastic astrocytoma. A further clinical trial with trabedersen to treat glioblastoma patients is in preparation.

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Phase Forward Signs Multi-Year, Multi-Million Dollar Agreement with Novo Nordisk to Expand Use of InFormT Electronic Data Capture Product

Phase Forward (NASDAQ: PFWD), a leading provider of data management solutions for clinical trials and drug safety, today announced a multi-year, multi-million dollar enterprise license and services agreement with Novo Nordisk, expanding the existing relationship between the two companies. Novo Nordisk plans to use Phase Forward's InForm™ electronic data capture (EDC) product as the default data capture system across all clinical trial phases, from Phases I through IV.

 

Since signing an application service provider (ASP) arrangement in mid-2006, Novo Nordisk has successfully implemented and integrated global InForm studies with internal systems. Novo Nordisk is currently using InForm to support trials in more than 30 countries.

 

"We've had a very successful collaboration with Phase Forward over the last three years, and look forward to expanding the relationship," said Henrik Lynge, Head of Clinical System Management in Novo Nordisk. "InForm's ability to easily integrate with other in-house systems and the product's scalability have been crucial to the implementation, enabling our team to streamline data collection for complex studies spanning multiple geographies."

 

"Novo Nordisk is a global leader in diabetes care," said Bob Weiler, chairman and CEO of Phase Forward. "We're pleased to be supporting their efforts to constantly advance the treatment options for a disease that affects quality of life for millions of people worldwide."

 

Novo Nordisk is a healthcare company and a world leader in diabetes care. In addition, Novo Nordisk has a leading position within areas such as haemostasis management, growth hormone therapy and hormone replacement therapy. Novo Nordisk manufactures and markets pharmaceutical products and services that make a significant difference to patients, the medical profession and society. With headquarters in Denmark, Novo Nordisk employs more than 27,000 employees in 81 countries, and markets its products in 179 countries. Novo Nordisk's B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol 'NVO'. For more information, visit novonordisk.com.

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Biotech initiates clinical trials with IL-6 and TNF-alpha inhibitor for RA

AnaMar Medical takes significant step with New Oral Cytokine Inhibitor to Treat Rheumatoid Arthritis

 

Göteborg, Sweden, April 27, 2009-- AnaMar Medical, a Swedish biotech company, today received approval from the UK Medicines and Healthcare products Regulatory Agency (MHRA[1]) to initiate clinical trials of AMAP102, a new oral drug candidate for the treatment of rheumatoid arthritis (RA) which affects an estimated 21 million people worldwide.[2]

 

AMAP102 works by inhibiting interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), two key cytokines associated with inflammation. AMAP102 has also shown an effect on pain.[3] AMAP102 acts on the aggressive synovial cells and decreases the production of pro-inflammatory mediators such as IL-6 and TNF-α, thereby hampering local joint inflammation and destruction and potentially preventing long-term damage and relieving certain systemic effects in RA.

 

"After the successful pre-clinical development, AMAP102 holds promise as a novel treatment for RA and is now ready to be tested in a 'First in Man' study," said Gunilla Ekström, Vice President R&D, AnaMar Medical AB. "The aim of the study is to establish the safety and tolerability of the compound as well as pharmacokinetics to support further clinical trials."

 

In pre-clinical studies, AMAP102 has performed strongly in multiple disease models for RA. The Phase I trial of AMAP102 will be conducted in the UK, starting April 27th 2009.

 

Targeting the IL-6 and TNF-α cytokines has proven to be an efficient treatment for RA with significant data demonstrating the efficacy of anti-IL-6 receptor antibodies and anti-TNF therapies. IL-6 is one of the most abundant cytokines found in both the joint and blood of patients with active RA.4 Higher levels of IL-6 and IL-6 receptor have been found in the serum of patients with RA which has been found to correlate with disease activity[4] and radiological joint damage.[5]

 

"The last decade has seen substantial development within the treatment of RA with the introduction of biologics," said Ingemar Petersson, MD, PhD, Consultant rheumatologist, Ass. Professor, Dept. Orthopedics and Rheumatology, Lund University Hospital, Sweden; Member of the Board, AnaMar Medical AB. "However, it is essential to continue the research and development of new compounds with different modes of action and administration to further improve outcomes for people with RA who have failed previous conventional and biologic therapies."

 

Although cytokine blocking treatments are effective, some patients have refractory disease and fail to respond to injectable protein therapies[6] and for others treatment is discontinued because of side effects. Many patients fail to respond to multiple DMARDs, creating an unmet medical need and opportunity for an oral, small molecule such as AMAP102 for this patient population.

 

"It is tremendously exciting for AnaMar to make the first move into clinical trials, and a clear confirmation that our pre-clinical development has been successful. With clinical effects documented, we will be looking for partnership for continued development of AMAP102, as well as our other compounds in late pre-clinical phase," said Owe Gårlin, CEO AnaMar Medical.

 

AnaMar Medical focuses on diagnosis and treatment of chronic joint diseases. The company has a broad portfolio of five drug development projects and three biomarkers originating from academic institutions and selected partners.

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Almac Clinical Technologies, PHT Team to Improve Clinical Trial Productivity

Almac Clinical Technologies and PHT Corp. have announced an alliance to improve clinical trial productivity through a variety of education initiatives and data integration efforts.
 
The initiatives and data integration efforts are expected to reduce clinical trial site burdens and improve study data collection and reporting.
 
As per the agreement, the companies will provide consultation with clinical trial sponsors on the difficult question of selecting the appropriate technology for studies involving electronic patient-reported outcomes (ePRO).
 
Currently, sponsors face challenges relating to the choice of using either a handheld device or an IVR or Web response system to capture ePRO data in their trials.
 
PHT and Almac plan to offer joint consultation with clients upon request to help clients better understand this issue. Also, both the companies are expected to conduct several workshops and panel sessions on this topic at industry events in 2009-10.

 
The integration of Almac's patient screening and randomization data with PHT's handheld devices for ePRO studies is the first joint initiative.
 
Sponsors working with both the companies will be provided the opportunity to have real-time data feeds from Almac's integrated IVR/IWR technology directly into PHT's handheld ePRO product suite - the LogPad and SitePad Systems.
 
"Our partnership with Almac offers added value for both sponsors and sites with one less data source to reconcile and the removal of a manual data entry step," said Philip Lee, CEO of PHT, adding that both the companies are helping sponsors and sites remove time-consuming data cleaning tasks to focus on what they care about most.
 
Whenever a patient is screened and randomized, Almac will send PHT real-time automated feeds. Officials said that this will improve data quality for sponsors and increase clinical trial sites' productivity. The integration is expected to eliminate the need for sites to manually enter in the same information provided by the Almac IVR system into the LogPad,
 
PHT and Almac are expected to launch their integrated offering by mid-2009.

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Intarcia Therapeutics, Inc. Announces Completion of Enrollment of ITCA 650 Phase 1b Study for the Treatment of Type 2 Diabetes

Intarcia Therapeutics, Inc. has announced the completion of patient accrual to a phase 1b clinical study evaluating ITCA 650 (DUROS(R) continuous delivery of exenatide). The study is being conducted at multiple centers in the United States and involves the treatment of 44 patients with type 2 diabetes for a period of 4 weeks.

 

Intarcia began the development of ITCA 650 in 2007 after acquiring an exclusive worldwide license to the DUROS delivery technology. The DUROS delivery technology consists of the DUROS device, a matchstick-size miniature osmotic pump that is inserted subcutaneously to provide continuous and consistent drug therapy, and proprietary formulation technology that maintains stability of therapeutic proteins and peptides at human body temperature for extended periods of time. Exenatide, the active agent in ITCA 650, has been approved in the US, Europe and many other markets and is currently marketed as a twice-daily self-injection therapy for type 2 diabetes.

 

Intarcia's phase 1 study is evaluating the safety and pharmacokinetics of ITCA 650 at several doses over a treatment period of 4 weeks. ITCA 650 therapy is administered for the full course of therapy with a single insertion of the DUROS device on day 1 and removal on day 29. Results of the phase 1 study will support selection of doses to be evaluated in a controlled phase 2 study planned for later in 2009 in which longer durations of treatment with a single ITCA 650 insertion will be evaluated. The DUROS technology can deliver up to a full year of therapy from a single ITCA 650 insertion. The goals of the ITCA 650 program are to enhance the therapeutic effects of exenatide by ensuring patient compliance and providing more consistent, round-the-clock therapeutic drug levels; and to reduce side effects, including nausea, associated with high peak levels of exenatide exposure observed with injection administration. Unlike other extended delivery technologies such as polymers or albumin fusion, DUROS delivery allows for steady state drug delivery upon insertion and near immediate withdrawal of therapy to manage side effects, if required.

 

"We are very pleased with the rapid progress the Company has made with ITCA 650," said Alice Leung, President & CEO of Intarcia. "Our team has demonstrated the great potential for DUROS delivered therapies in advancing this important treatment candidate for type 2 diabetes patients from an idea to clinical stage development in 18 months."

 

ITCA 650 is the second DUROS delivery program Intarcia has moved into clinical development. In December 2008, Intarcia also completed enrollment of a phase 1b study for ITCA 638, which involves DUROS delivery of omega interferon for the treatment of chronic hepatitis C infection. "Many patients with type 2 diabetes are forced to manage dosing schedules and side effects of multiple drug therapies simultaneously to adequately control their disease," commented Ken Luskey, M.D., VP, Clinical Research at Intarcia. "We believe ITCA 650 will deliver improved glycemic control and provide a better tolerated, more convenient treatment option."

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Drug inhibits neuroblastoma blood supply in pre-clinical tests

Reduces tumor growth by 75 percent by disrupting blood vessel formation

 

Researchers from the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center have found a way to prevent blood vessels from aiding the growth of neuroblastoma, a childhood cancer. The pre-clinical study was presented today in a platform session at the 22nd annual meeting of the American Society of Pediatric Hematology/Oncology.

 

Investigators at the Children's Cancer Hospital at M. D. Anderson have discovered that the drug, AMD3100, hinders the formation of tumor blood vessels and reduces human neuroblastoma tumor growth by more than 75 percent in mice.

 

The drug blocks interaction between SDF-1a and its receptor CXCR4. This pathway plays an important role in signaling cells to different areas of the body. More specifically, the study suggests that SDF-1a plays a role in differentiating and/or attracting pericyte-like cells to neuroblastoma tumors.

 

Pericytes are essential for organizing blood vessels to feed tumors. Without pericytes, blood vessels are dysfunctional and tumors are left without a vital blood source. This study found that AMD3100 decreased the number of pericyte-like cells in neuroblastoma tumors by close to 90 percent.

 

"AMD3100 works by shutting down the process that tumors need to set up vascular systems," says Patrick Zweidler-McKay, M.D., Ph.D., assistant professor at the Children's Cancer Hospital and senior investigator on the study. "The drug doesn't kill neuroblastoma cells directly, but it prevents tumors from growing rapidly by disrupting their blood supply."

 

In tissue culture, investigators were also able to show how AMD3100 prevented neuroblastoma cells from migrating toward SDF-1a ligands. SDF-1a is present at high levels in the bone marrow, one of two areas where neuroblastoma most commonly metastasizes.

 

"There is the possibility that this therapy could help prevent neuroblastoma metastasis to the bone marrow. However, more studies are needed to investigate this theory," says Zweidler-McKay.

 

According to the American Cancer Society, approximately 650 children, mainly under the age of five, are diagnosed with neuroblastoma in the United States each year. Close to two-thirds of these children are diagnosed after the cancer has metastasized to other parts of the body. For these patients with high-risk neuroblastoma, long-term survival is less than 40 percent because the tumors are often resistant to traditional chemotherapy.

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Almac and PHT Announce Formal Alliance to Improve Clinical Trial Data Quality

Almac Clinical Technologies and PHT Corporation announced a formal alliance today to improve clinical trial productivity through a variety of education initiatives and data integration efforts that will reduce clinical trial site burdens while improving study data collection and reporting.

 

As part of their alliance activities, PHT and Almac have agreed to provide consultation with clinical trial sponsors on the difficult question of choosing the appropriate technology for studies involving electronic patient-reported outcomes (ePRO). Currently, sponsors face challenges relating to the choice of using either a handheld device or an interactive voice or Web response system to capture ePRO data in their trials. To help clients better understand this issue, PHT and Almac will offer joint consultation with clients upon request and conduct several workshops and panel sessions on this topic at industry events in 2009-10.

 

The first joint data initiative involves integration of Almac's patient screening and randomization data with PHT's handheld devices for ePRO studies. Sponsors who choose to work with both Almac and PHT will be afforded the opportunity to have real-time data feeds from Almac's industry-leading integrated IVR/IWR technology directly into PHT's market-leading handheld ePRO product suite, the LogPad® and SitePad™ Systems. Almac will send PHT real-time automated feeds whenever a patient is screened and randomized, improving data quality for sponsors and increasing clinical trial sites' productivity. The integration will remove the need for sites to manually enter in the same information provided by the Almac IVR system into the LogPad, thereby reducing data entry errors that can be costly to remediate. Future efforts will involve deeper data integration, including seamless integration between Almac's study data with that collected by PHT and EDC vendors. Both Almac and PHT's advanced technology offerings consistently integrate with other systems using CDISC standards.

 

Philip Lee, CEO of PHT, comments about the benefits that the alliance will provide to clients. "Our customers are constantly looking for ways to integrate multiple streams of eClinical data and reduce the data entry burden on sites. Our partnership with Almac offers added value for both sponsors and sites with one less data source to reconcile and the removal of a manual data entry step. Together, PHT and Almac are helping sponsors and sites remove time-consuming data cleaning tasks to focus on what they care about most -- the health and safety of patients and conducting rigorous scientific research."

 

Almac Clinical Technologies' President Jim Murphy believes that deeper integration of data between best-of-breed technology vendors offers tremendous benefits for sponsors. "Obtaining the highest quality data from vendors and sites is the primary need of pharmaceutical study sponsors. This alliance satisfies that need by integrating data from the highest quality clinical technology companies. The Almac/PHT alliance offers sponsors an opportunity to resist compromising data quality and trading off high quality technology or customer service to work with one vendor who offers all technologies for data collection, but is not best-of-breed in all or any of them."

 

PHT and Almac plan to launch their integrated offering by mid-2009. Further details about the alliance and joint initiatives are available by contacting either PHT or Almac Clinical Technologies.

 

Both Almac and PHT will be exhibiting at next week's Partnerships with CRO's Conference; come visit them for more information at Booth's 317 and 520.

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Invivodata Certified To Deliver EXACT In COPD Trials

invivodata inc., the industry leader in electronic Patient-Reported Outcomes (ePRO) solutions and services for global clinical research, announced that it has completed a certification program to provide the EXAcerbations of Chronic pulmonary disease Tool (EXACT) on its DiaryPRO(C) field-based ePRO system.

 

The EXACT is a Patient-Reported Outcome (PRO) measure for evaluating the frequency, severity, and duration of acute exacerbations of chronic obstructive pulmonary disease (COPD) and chronic bronchitis (AECB) in international clinical trials. Developed by United BioSource Corporation's (UBC) Center for Health Outcomes Research, with significant input from clinical and instrument development experts and involvement of the U.S. Food and Drug Administration (FDA), the EXACT is the industry's only standardized tool for measuring exacerbations of COPD.

 

"Being a certified provider of this unique tool enables us to offer our global customers a reliable and efficient means of implementing the EXACT in their clinical trials as they develop more effective COPD treatments," said Tom Henson, invivodata vice president of marketing.

 

COPD, which includes chronic bronchitis and emphysema, is a disease characterized by obstruction to airflow that interferes with normal breathing. COPD is the fourth leading cause of death in the world, and further increases in the prevalence and mortality of the disease are predicted in the coming decades. In the United States 11.4 million Americans are diagnosed with the disease with over 122,000 deaths each year. Clinical researchers have put significant effort into developing new COPD treatments, as evidenced by the 33% increase in clinical trials for new COPD medications since 2006.

 

"We are pleased to certify invivodata on the electronic delivery of the EXACT and to continue our work with them in assuring high quality data in all types of clinical studies in which the instrument is used," said Dr. Nancy Kline Leidy, senior vice president of scientific affairs for UBC and Principal Investigator of the EXACT-PRO Initiative. "We have found their e-diary device meets the needs of the EXACT and is ready for use in international trials."

 

Licensing agreements to use the EXACT are obtained directly from United BioSource Corporation.

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OctoPlus N.V. (NL) - OctoPlus' licensee Biolex presents Locteron Phase IIa results at EASL conference

OctoPlus N.V. ("OctoPlus" or "the Company") (Euronext: OCTO) announces today that its licensee Biolex Therapeutics (see separate Biolex press release on www.biolex.com) will present the results from its United States Phase IIa clinical study (the "PLUS" study) with Locteron® today at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL) in Copenhagen, Denmark. Results of this study suggest that Locteron may result in less frequent flu-like symptoms when compared to pegylated interferon products.

 

The PLUS Phase IIa clinical study was conducted in the United States in 32 chronic hepatitis C patients who had failed prior treatment. The study was designed to evaluate the safety and tolerability of Locteron, and to directly compare Locteron with the current standard of care. Patients were randomised to receive either Locteron (administered once every two weeks) or PEG-Intron® (administered once per week). The Locteron doses evaluated in the PLUS study were 320 µg and 640 µg, and patients also received oral, weight-based ribavirin. Patients were treated for four weeks with an additional two weeks of follow up evaluation.

 

Flu-like symptoms were reported to be less frequent and milder in both of the Locteron cohorts of the study. The total severity score for flu-like symptoms for patients in the 320 µg cohort of Locteron was 80% lower than the severity score for the PEG-Intron cohort (severity score was based on number of occurrences adjusted for severity rating of adverse event). The total severity score for patients in the 640 µg cohort of Locteron was 30% lower than the severity score for the PEG-Intron cohort. Injections site reactions and common hematological parameters among the Locteron cohorts and the PEG-Intron cohorts were comparable. Anti-viral effects were also comparable among the Locteron and PEG-Intron cohorts.

 

Simon Sturge, CEO of OctoPlus: "These results support Locteron's potential improved tolerability profile that has been suggested in previous clinical studies and further validate the added value of our controlled release drug delivery technologies in the development of improved injectable therapeutics."

 

Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.

 

For further information, please contact: Rianne Roukema, Corporate Communications: telephone number +31 (71) 524 1071 or e-mail IR@octoplus.nl

 

About Locteron Locteron is a controlled release interferon alpha designed to improve patient care in the treatment of hepatitis C through a more favorable side-effect profile and dosing convenience compared to existing pegylated interferon products. In contrast to Locteron's controlled release mechanism, the currently approved products Pegasys® and PEG-Intron, and the investigational product Albuferon® are immediate release products that lack a controlled release mechanism. Interferon alpha serves as the foundation of current combination therapy for hepatitis C patients, and all major hepatitis C drug candidates currently in clinical trials are being studied in combination with interferon alpha. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach US$ 6 billion by 2016.

 

Locteron combines OctoPlus' proprietary drug delivery technology PolyActive® with BLX-883, a recombinant interferon alpha produced by Biolex in its patented LEX System(SM). Locteron is configured to allow dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled release mechanism results in the gradual release of interferon alpha to patients over the duration of two weeks and avoids the early peak blood plasma levels of the active interferon that characterise pegylated interferons and Albuferon. This controlled release mechanism is designed to reduce the frequency, duration and severity of side effects, including flu-like symptoms, commonly experienced by patients treated with pegylated interferons and with Albuferon.

 

Three clinical trials with Locteron have been completed to date, and a Phase IIb study is currently ongoing in 100 chronic genotype-1 hepatitis C patients in the United States and Europe.

 

About Biolex Therapeutics Biolex is a clinical-stage biopharmaceutical company that uses its patented LEX System(SM) to develop hard-to-make therapeutic proteins and to optimize monoclonal antibodies. The LEX System is a novel technology that genetically transforms the aquatic plant Lemna to enable the production of biologic product candidates.

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Drug therapy reduces neuroblastoma tumor growth in pre-clinical investigation

Researchers from the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center have discovered a new drug combination that significantly hinders tumor growth in neuroblastoma, a childhood cancer. The study was presented today at the 22nd annual meeting of the American Society of Pediatric Hematology/Oncology (ASPHO).

 

By combining a novel multi-kinase inhibitor, vandetanib, with 13-cis-retinoic acid (CRA), a drug often used for severe acne, researchers from the Children's Cancer Hospital at M. D. Anderson found that the two therapies reduced neuroblastoma tumors by 86 percent in pre-clinical tests.

 

Peter Zage, M.D., Ph.D., who specializes in neuroblastoma at the Children's Cancer Hospital, received this year's Young Investigator Award from ASPHO and was selected to present his research today in a special platform session.

 

"By itself, vandetanib inhibited tumor growth by two-thirds and decreased blood vessel formation around neuroblastoma tumors in mice," says Zage. "When combined with CRA, the impact was even greater on tumor growth."

 

Vandetanib blocks a family of endothelial growth factors and receptors that promote tumor growth as well as the RET oncogene, which can signal neuroendocrine cells to develop into neuroblastoma cells. Although commonly used in treatment for neuroblastoma, CRA by itself does not have a significant impact against the childhood cancer. However, it works in combination therapy to differentiate neuroblastoma cells into mature benign neural cells.

 

Currently, there is a Phase I clinical trial open for children with multiple-relapsed neuroblastoma to further study the new therapy combination. This trial is the first in the world to test vandetanib in children.

 

Zage says in addition to the pediatric patients enrolled in the Phase I trial, adult patients with lung cancer have received vandetanib and have tolerated the novel drug well.

 

According to the American Cancer Society, approximately 650 children, mainly under the age of five, are diagnosed with neuroblastoma in the United States each year. Close to two-thirds of these children are diagnosed after the cancer has metastasized to other parts of the body. For these patients with high-risk neuroblastoma, long-term survival is less than 40 percent because the tumors are often resistant to traditional chemotherapy.

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Human Genome Sciences Reports Positive Late-Breaker Results at EASL from ACHIEVE Phase 3 Trials of Albuferon(R) in Patients with Chronic Hepatitis C

- With half as many injections, in two pivotal Phase 3 trials, Albuferon (albinterferon alfa-2b) met the primary efficacy endpoint of sustained virologic response comparable to Pegasys (peginterferon alfa-2a) -

 

- Patients receiving 900-mcg Albuferon had comparable rates of serious and/or severe adverse events across the two Phase 3 trials, versus peginterferon alfa-2a -

 

- Submission of global marketing applications planned in fall 2009 -

 

ROCKVILLE, Md., April 25 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI) today reported that the final results of two pivotal Phase 3 trials demonstrate that Albuferon(R) (albinterferon alfa-2b) met its primary endpoint of non-inferiority to peginterferon alfa-2a (Pegasys) in the treatment of patients with chronic hepatitis C. The Phase 3 results were the subject of two late-breaker oral presentations today in Copenhagen at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL). Albinterferon alfa-2b is being developed by HGS and Novartis under an exclusive worldwide co-development and commercialization agreement entered into in June 2006.

 

"The Phase 3 data presented at EASL show that Albuferon, with half the injections, achieved a rate of sustained virologic response comparable to Pegasys," said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. "Importantly, the rates of serious and/or severe adverse events were also comparable in these studies. We plan to file global marketing applications in fall 2009, following discussions with regulatory authorities - and we believe that Albuferon, assuming licensure, could become a leading treatment for chronic hepatitis C."

 

The Phase 3 studies, known as ACHIEVE 1 and ACHIEVE 2/3, evaluated albinterferon alfa-2b vs. peginterferon alfa-2a, in combination with ribavirin, for use in the treatment of interferon-naive patients with chronic hepatitis C. ACHIEVE 1 was conducted in patients infected with genotype 1 virus, and ACHIEVE 2/3 was conducted in patients with genotypes 2 and 3 virus. The two studies treated a combined total of 2255 treatment-naive patients.

 

"The results of two Phase 3 trials demonstrate that 900-mcg albinterferon alfa-2b administered every two weeks provides efficacy comparable to peginterferon alfa-2a administered weekly, with a positive safety profile," said David Nelson, M.D., Professor of Medicine, Medical Director of Liver Transplantation, and Chief of the Hepatobiliary Disease Section, University of Florida. Dr. Nelson presented the results from ACHIEVE 2/3.

 

Stefan Zeuzem, M.D., Professor of Medicine and Chief, Department of Medicine, J.W. Goethe University Hospital, Frankfurt, Germany, presented the ACHIEVE 1 results, and said, "The data presented at EASL suggest that albinterferon alfa-2b has the potential to become an important and novel treatment option for patients with chronic hepatitis C."

 

Phase 3 Efficacy Findings

 

Based on an intention-to-treat (ITT) analysis, the data presented at EASL demonstrate that albinterferon alfa-2b met its primary efficacy endpoint of non-inferiority to peginterferon alfa-2a in both ACHIEVE 1 and ACHIEVE 2/3:

 

    * ACHIEVE 1: 48.2% (213/442) of patients in the 900-mcg albinterferon alfa-2b treatment group achieved sustained virologic response (SVR), vs. 51.0% (225/441) in the peginterferon alfa-2a treatment group. The primary analysis, which was adjusted for baseline stratification factors, showed a difference in SVR rates of -1.8% (95% CI -8.1%, 4.5%, p=0.0008 for non-inferiority).
    * ACHIEVE 2/3: 79.8% (249/312) of patients achieved SVR in the 900-mcg albinterferon alfa-2b treatment group, vs. 84.8% (263/310) in the peginterferon alfa-2a group (p=0.0086 for non-inferiority). The primary analysis, which was adjusted for baseline stratification factors, showed a difference in SVR rates of -4.8% (95% CI -10.7%, 1.1%, p=0.0086 for non-inferiority).
          o An unexpectedly high and still unexplained SVR rate for peginterferon alfa-2a in the Asian region fully accounted for the observed SVR difference between the two drugs in the ACHIEVE 2/3 study.
          o In non-Asian regions, 79.8% (174/218) of patients achieved SVR in the 900-mcg albinterferon alfa-2b treatment group, vs. 80.5% (178/221) in the peginterferon alfa-2a group. In Asia, 79.8% (75/94) of patients achieved SVR in the 900-mcg albinterferon alfa-2b treatment group, vs. 95.5% (85/89) in the peginterferon alfa-2a group.

 

Phase 3 Safety Findings

 

Across the two albinterferon alfa-2b Phase 3 trials, rates of serious and/or severe adverse events were comparable in all dose groups, including 21.2% (160/755) for 900-mcg albinterferon alfa-2b, and 20.8% (156/750) for 180-mcg peginterferon alfa-2a.

 

The incidence of fatality in the albinterferon alfa-2b Phase 3 trials was rare. All-cause mortality rates were 0.13% (1/755) for 900-mcg albinterferon alfa-2b every two weeks, and 0.27% (2/750) for 180-mcg peginterferon alfa-2a.

 

Rates of discontinuation due to adverse events across the two studies were 8.1% (61/755) for 900-mcg albinterferon alfa-2b, vs. 3.9% (29/750) for peginterferon alfa-2a. The causes of discontinuation for both drugs were those typical for interferon-based therapy.

 

Overall, adverse events observed were those typically associated with interferon therapy, and most were similar for 900-mcg albinterferon alfa-2b and peginterferon alfa-2a.

 

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Nymox wins approval to initiate Phase III BPH trials

Screening and enrollment of patients to formally begin in the next two weeks

 

Nymox Pharmaceutical has received the investigational review board's approval to begin NX02-0017, the first Phase III US clinical trial for NX-1207, the company's investigational drug for benign prostatic hyperplasia. Screening and enrollment of patients will formally begin in the next two weeks.

 

The company will undertake two pivotal Phase III US clinical trials for NX-1207, with a total of 1,000 patients. The protocol and patient materials have been officially approved by the investigational review board. Currently there are agreements with 60 investigational sites in the US. The company expects the number of clinical trial sites to be increased to up to 100 investigational sites.

 

The Phase III trials for NX-1207 will test the safety and efficacy of the drug treatment of benign prostatic hyperplasia (BPH) as compared to placebo. Efficacy will be determined by symptomatic improvement, using the American Urological Association BPH Symptom Index, which measures the severity of the irritative and obstructive urinary symptoms of BPH, including frequency, urgency, intermittency, hesitancy, sensation of incomplete voiding, weak stream, and nocturia.

 

The trials will also investigate the drug's effect on prostate volume, urinary maximum flow rate, and several other pertinent measurements, the company added.

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PhRMA Revises Clinical Trial Conduct and Reporting Policy

Pharmaceutical Research and Manufacturers of America (PhRMA) members will begin to register some Phase 1 clinical trials on public Web sites, if the trial involves subjects with the disease or condition being studied.

 

PhRMA announced the revision of its Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results at the National Institutes of Health's (NIH's) April 20 public meeting on the expansion of ClinicalTrials.gov. "PhRMA members will register all clinical trials in patients including some early Phase 1 clinical trials," Jeffrey Francer, PhRMA assistant general council, said at the public hearing.

 

Francer said the revised principles, which take effect Oct. 1, also call for companies to provide result summaries for interventional clinical trials involving patients for approved medicines as well as those medicine's whose research programs are discontinued. "Going forward, PhRMA members will provide summaries of safety and effectiveness data for clinical trials in patients whenever drug development is discontinued," he said. "We are hopeful that NIH will help PhRMA members to post voluntarily on ClinicalTrials.gov information on early stage clinical trials in a way that will not threaten the viability of future research."

 

In announcing the revisions, PhRMA said it is "moving in lockstep with medical journal editors by adopting the authorship standards of the International Committee of Medical Journal Editors (ICMJE)." The revised principles state that "when authors submit a manuscript to a medical journal, whether an article or a letter, they are responsible for disclosing all financial and personal relationships that might bias their work. To prevent ambiguity, authors should state explicitly whether potential conflicts do or do not exist." Authors also are expected to identify individuals who provide writing or other assistance and disclose the funding source for this assistance.

 

"Under these revised principles, only individuals who make substantial contributions to medical manuscripts will be recognized as authors," PhRMA said.

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Pregnancy Hormone HCG Protects Against Breast Cancer Even In Short-term Treatments

One of the most effective ways to prevent breast cancer is through a full-term pregnancy at an early age. Studies out of Fox Chase Cancer Center have linked this protective effect to the presence of human chorionic gonadotropin (hCG), a hormone produced by the placenta to maintain the early stages of pregnancy.

 

Their findings in an animal model of breast cancer showed that rats exposed to hCG over a 21 day period (the length of rat pregnancy), are far less likely to develop breast cancer when exposed to a known carcinogen.

 

Today, at the 100th Annual Meeting of the American Association for Cancer Research. Johana Vanegas, M.D., a research associate at Fox Chase, presents findings suggesting that even a much shorter exposure to hCG can prevent breast cancer in rats.

 

Venegas is a member of the laboratory of Jose Russo, M.D. and Irma Russo, M.D., who were the first scientists to propose hCG as an anti-cancer agent. Their studies have shown that hCG offers lasting, protective changes within breast tissue. Clinical trials of hCG in women, based on their work, are currently under way at three locations, nationally, including Fox Chase Cancer Center, and in one European country. The hCG hormone is an FDA-approved agent frequently used for fertility treatments.

 

"The ability to replicate the naturally protective effects of pregnancy against breast cancer will hold a significant public health value," says Vanegas. "In order to translate our finding into humans, a clinical trial with hCG as a preventive agent against breast cancer, is already ongoing in pre-menopausal women with no previous pregnancy."

 

Vanegas and her colleagues studied virgin female rats, which had been divided into four groups: a control group, which did not receive hCG, and three groups that received hCG for five, ten or fifteen consecutive days. Following the treatment, each rat received a single dose of a breast cancer-inducing agent.

 

According to Vanegas, 90.9 percent of the rats in the control group developed breast tumors, compared to 71.4 percent, 57.1 percent, and 15.4 percent in the five, ten and fifteen day-treated animals, respectively. In addition, the average tumor size was also smaller in all the animals that received any of the three hCG treatments.

 

"The animals that received hCG, but still developed breast cancer did so much later than the control group, which further demonstrates the protective effects of hCG," Vanegas says. "While we don't foresee side effects among humans in using hCG, it is helpful to know that even smaller doses confer benefits on breast tissue."

 

Funding for this research comes from grants from the National Institutes of Health and the National Cancer Institute.

 

 

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Phase 1 malaria vaccine trial to begin

A U.S. biotechnology company says it will conduct the first clinical trial involving humans of a malaria vaccine that contains the whole malaria parasite.

 

Sanaria Inc. of Rockville, Md., said it is using a weakened form of the whole malaria parasite that's been harvested from irradiated mosquitoes. Other malaria vaccine candidates use only small portions of the parasite.

 

Sanaria said its vaccine will be assessed in 104 healthy volunteers beginning next month.

 

Myron Levine, director of the University of Maryland School of Medicine's Center for Vaccine Development said the Sanaria vaccine is based, in part, on findings from parallel studies conducted during the early 1970s by teams at the Center for Vaccine Development and the Naval Medical Research Center. Levine said those findings were never translated into a vaccine development effort because the task was considered to be impossible.

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Icagen Completes Enrollment in Phase II Allergen Challenge Asthma Trial

Icagen, Inc. has reported the completion of enrollment in the Company's Phase II proof-of-concept study of senicapoc in patients with allergic asthma. Initial results from this study are expected during the second half of this year.

 

As previously reported, the allergen challenge trial is a double-blind, placebo-controlled, parallel group study that is designed to assess the safety and efficacy of senicapoc administered orally on pulmonary function in patients with allergic asthma following exposure to a known antigen. Approximately 30 patients at two research centers in the United Kingdom were randomized in a 1:1 ratio to senicapoc or placebo. The primary efficacy analysis is the comparison between treatment arms of the late asthmatic response caused by inhalation of allergen, measured by percent change in Forced Expiratory Volume 1 (FEV1), the amount of air that can be forcefully exhaled in one second. FEV1 is a standard, commonly used test to measure lung function.

 

In addition to the allergen challenge study, Icagen is also conducting a Phase II proof-of-concept study in patients with exercise-induced asthma. This study will enroll approximately 60 patients at multiple centers throughout the United States. Enrollment is proceeding according to expectations, with approximately one-half of the study subjects enrolled to date. Initial results from this study are expected during the second half of the year.

 

Senicapoc is a novel orally available small molecule inhibitor of the KCa3.1 potassium ion channel. Literature data suggests a potential role for inhibitors of KCa3.1 in the treatment of a wide variety of inflammatory and immune-mediated diseases, including asthma. Results from preclinical studies demonstrated the ability of senicapoc to reverse antigen-induced increases in airway resistance and airway hyper-reactivity.

 

"We are very pleased to have achieved another important milestone in the development of senicapoc for asthma," stated Seth V. Hetherington, M.D., Senior Vice President of Clinical Development and Regulatory Affairs at Icagen. "With its novel mechanism of action, senicapoc represents a potential new oral therapy for asthma patients, and we look forward to having the results of this trial, which we expect to be available later this year."

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Impact Medical Solutions Updates Pilot Clinical Trial of MPR System

MPR technology will be the first quantitative tool developed for assisting in the diagnosis of the presence or absence of a musculoskeletal dysfunction (sprain/strain injuries) and will substantially improve the accuracy of diagnosis, rehabilitation and case management decisions

 

Impact Medical Solutions, Inc., an information technology company, today updated the status of its pilot clinical trial of the Company's proprietary information technology platform, Muscle Pattern Recognition (MPR). MPR is a unique clinical tool that analyzes patterns of muscle recruitment. It provides detailed physiological information on muscle function that can assist in the diagnosis and treatment of back and neck injuries and illness.

 

"The MPR technology will be the first quantitative tool developed for assisting in the diagnosis of the presence or absence of a musculoskeletal dysfunction (sprain/strain injuries) in a patient population," stated Dr. Alan Goldman, Vice President, Clinical and Medical Affairs for Impact Medical Solutions.

 

"The availability of such an evaluation tool to a healthcare provider for patients with soft tissue, non-surgical neck or back complaints will substantially improve the accuracy of diagnosis, rehabilitation and case management decisions," added Goldman.

 

The Company announced that it had recruited its 150th trial subject since the trial was first announced on February 25, 2009 and that patient recruitment continues to be strong.

 

"We are ahead of schedule as far as testing is concerned and we're pleased to report that the MPR System is performing at or above our expectations, and our expectations are high," said Wayne Cockburn, President and CEO at Impact Medical Solutions.

 

"There is currently a two to three week waiting list to get into our trial and we anticipate this trend to continue. We are planning on opening a second test site in Southern California within the next several weeks and a third site in Michigan during the summer. We expect the results of this pilot trial will be used in our submission to FDA later this year," Cockburn adds.

 

The pilot clinical trial is currently being conducted at the Utah Spine and Joint Center in Salt Lake City, Utah and the total trial is expected to involve several hundred subjects, many of whom are experiencing chronic back pain.

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ANA598 Demonstrates Potent Antiviral Activity at all Dose Levels in Completed Phase Ib Study in Hepatitis C Patients

Anadys Pharmaceuticals, Inc. has announced that ANA598, the Company's investigational non-nucleoside polymerase inhibitor, demonstrated potent antiviral activity at all dose levels and was well tolerated in a Phase Ib study in which patients chronically infected with the Hepatitis C virus (HCV) were treated for three days. The results from the recently completed study are being presented today during the late-breaker poster session at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL) in Copenhagen, Denmark.

 

In the study, ANA598 treatment resulted in rapid and sustained reductions in HCV RNA with median reductions at end of treatment (Day 4) exceeding 2 log10 (>99%) at all dose levels. At 200 mg bid (twice-daily), the median viral load reduction was 2.4 log10 (range of 0.4 to 3.4); at 400 mg bid, 2.3 log10 (range of 1.6 to 3.5); and at 800 mg bid, 2.9 log10 (range of 2.2 to 3.4). Genotype 1a patients demonstrated median reductions of 1.4 log10, 1.8 log10, and 2.5 log10 at 200, 400 and 800 mg bid, respectively. In 10 of the 12 genotype 1a patients who received ANA598, viral load was still declining at the end of the three days of treatment. Genotype 1b patients demonstrated median reductions of 2.6 log10, 2.5 log10, and 3.2 log10, at 200, 400 and 800 mg bid, respectively. No patient showed evidence of viral rebound while on ANA598. ANA598 was well-tolerated in this short term study and there were no serious adverse events.

 

Steve Worland, Ph.D., Anadys' President and CEO, commented that "The potent antiviral activity demonstrated at all three doses in this study is very encouraging for the prospects of ANA598 when used in combination with other HCV agents. With the successful conclusion of this study in patients and the 14-day study in healthy volunteers, the positive 13-week animal toxicology results and ongoing manufacturing activities, the ANA598 program continues on track to be ready for Phase II in mid-2009."

 

The Phase Ib study was a randomized, double-blind, placebo-controlled, multiple ascending dose trial conducted to evaluate the safety, tolerability and antiviral activity of orally administered ANA598 in treatment-naive patients with chronic HCV genotype 1 infection. Patients were treated with ANA598 capsules (or matching placebo) at doses of 200 mg, 400 mg or 800 mg bid for three days. 35 patients participated in the study, with 11 receiving 200 mg bid, eight receiving 400 mg bid, eight receiving 800 mg bid and eight receiving placebo (with none of the patients receiving placebo showing an end of treatment response greater than 0.2 log10 reduction in viral load). Viral load at Day 4 (12 hours after the last dose) was compared to baseline HCV RNA levels.

 

"We're very pleased with the antiviral activity and safety of ANA598 in this study," commented James Freddo, M.D., Senior Vice President, Drug Development and Chief Medical Officer. "We believe the data continue to position ANA598 as a leading non-nucleoside polymerase inhibitor in development for the treatment of HCV, and we look forward to investigating ANA598 in longer-term studies in combination with current standard of care."

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TOPICA Begins Phase 2 Clinical Trial of Potent Antifungal, Luliconazole, in Athlete's Foot

TOPICA Pharmaceuticals today announced the enrollment of patients in a Phase 2 clinical trial evaluating luliconazole for the treatment of tinea pedis (athlete's foot). Luliconazole, the company's lead product candidate, is the one of the most potent and broad spectrum molecules in the imidiazole class of antifungal agents, giving it the potential to provide physicians and patients with a needed topical solution to a variety of skin and nail fungal infections.

 

"The initiation of this trial represents a significant milestone for TOPICA as we begin our U.S. clinical development program of this promising drug candidate, which already has been proven in millions of patients in Japan," said Greg Vontz, president and chief executive officer of TOPICA. "We expect to complete this trial by the end of this year, potentially enabling us to initiate our pivotal Phase 3 clinical trial in 2010."

 

Phase 3 data from clinical studies conducted in Japan demonstrated that luliconazole successfully treated tinea pedis in half the time of commonly prescribed products. Since the 2005 approval of luliconazole in Japan for the treatment of tinea infections, more than 4 million patients have been safely treated with luliconazole. TOPICA has an exclusive license to develop and market luliconazole in the Americas and Europe.

 

The Phase 2, multi-center, randomized, double blind, trial is evaluating the safety and optimal duration of 1 percent luliconazole cream administered once daily for 14 or 28 days in patients with tinea pedis. The primary efficacy endpoint is to achieve complete clearance of the infection at two weeks post treatment. Currently in the U.S. available prescription medications generally require treatment once or twice a day for up to four weeks to achieve this result. The company expects to enroll approximately 120 patients in the trial, which is being conducted at 5 clinical trial sites in the United States. For more details on the trial go to http://www.topicapharma.com and clink on the link for the trials posting on www.clinicaltrials.gov.

 

In addition, the company is developing luliconazole for onychomycosis (nail and nail bed fungal infections) and plans to move ahead with clinical development of onychomycosis shortly. The company's successful preclinical studies of luliconazole demonstrate that it has the ability to easily penetrate the toenail achieving rapid fungal eradication in the nail bed, as measured by MedPharm's in vitro ChubTur infected nail model. Luliconazole is also unique in that the molecule doesn't require devices, procedures or "delivery enhancement" to cross the nail. Onychomycosis affects approximately 35 million people in the U.S. Of those affected, it is estimated that 47 percent are not receiving treatment. The disease can cause extreme disfigurement of nails and can often result in pain. The potential annual U.S. market for onychomycosis treatment is estimated at approximately $3.0 billion.

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GTx Announces Toremifene 80 mg Phase III ADT Clinical Trial Data to be Presented at the Annual Meeting of the American Urological Association

GTx, Inc. has announced that data from the Phase III clinical trial evaluating toremifene 80 mg for the prevention of fractures in men with prostate cancer on androgen deprivation therapy will be the subject of an oral podium presentation at the 2009 Annual Meeting of the American Urological Association being held in Chicago April 25 - 30.

 

• Abstract #639 – "Positive fracture reduction trial of toremifene 80 mg in men on ADT demonstrates significant fracture risk in untreated placebo group"
• Sunday, April 26, 2009, 3:30 – 5:30 p.m. Central Time
• McCormick Place Chicago, Room W475 AB
  

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MediciNova Reports Final Data from Phase II MN-221 Emergency Department Clinical Trial (MN-221-CL-006); Hospitalization Rates Decrease 45 Percent With MN-221 Plus Standardized Care in Asthma Patients

MediciNova, Inc., a biopharmaceutical company that is publicly traded on the Nasdaq Global Market (Nasdaq:MNOV) and the Hercules Market of the Osaka Securities Exchange (Code Number: 4875), today announced final results from its Phase II clinical trial (MN-221-CL-006) evaluating MN-221 at planned escalating doses of 240 to 1,080 micrograms in patients with severe, acute exacerbations of asthma treated in Emergency Departments. The study included 29 (13 treated with standard care only and 16 treated with MN-221 plus standard care) patients with severe, acute exacerbations of asthma. All patients received standardized care consisting of inhaled albuterol, ipratropium and oral steroid treatment. No safety concerns with adding MN-221 to standardized care were identified following review of electrocardiogram (ECG), laboratory and Adverse Experience data. The hospitalization rate among patients treated with standardized care only was 46 percent (six of 13), which was the anticipated rate, compared to a hospitalization rate of 25 percent (four of 16) among patients receiving MN-221 plus standardized care. This represents a 45 percent reduction in hospitalization rate among patients treated with MN-221. All hospitalizations were due to asthma exacerbations which were judged to be unrelated to study medication and therefore do not raise safety concerns for adding MN-221 to standardized care. As specified in the protocol for this clinical trial, no inferential statistics (i.e., p-values) were calculated for this study. Improvement in forced expiratory volume in 1 second (FEV(1)) values generally appeared to be greater for patients receiving MN-221 in addition to standardized treatment.

 

"These clinical results are consistent with the interim data reported from this study in January and demonstrate the potentially beneficial effect of MN-221 in the treatment of severe, acute exacerbations of asthma," said Yuichi Iwaki, M.D., Ph.D., President and Chief Executive Officer of MediciNova, Inc. "The benign safety profile of MN-221 and the 45 percent reduction in hospitalization rate observed are encouraging."

 

MediciNova also announced that its MN-221-CL-007 study, a randomized, double-blind, placebo-controlled Phase II clinical trial designed to evaluate the safety and efficacy of MN-221 in patients with severe, acute exacerbations of asthma, has begun enrolling patients in the United States. The majority of investigators who participated in the MN-221-CL-006 study have rolled over to the MN-221-CL-007 study.

 

MediciNova expects to enroll approximately 200 patients at approximately 35 Emergency Department clinical sites, including the clinical sites rolled over from the MN-221-CL-006 study, in North America, Australia and New Zealand. The MN-221-CL-007 study is designed to compare standardized care to standardized care plus MN-221 at a dose of 1.2 mg administered over one hour. Once a patient has received the initial standardized care treatment regimen (consistent with the National Asthma Education and Prevention Program and the Global Initiative for Asthma (GINA) guidelines), the patient will be assessed for response to that treatment. If the patient's FEV(1) is less than or equal to 50 percent of predicted and the patient meets all other study entry criteria, the patient will be randomized to receive either MN-221 or placebo. Patients enrolled in the study will continue to receive standardized care as needed while receiving an intravenous infusion of MN-221 or placebo. The primary efficacy endpoint will be improvement in FEV(1). Enrollment of study participants began in April 2009 in the North American clinical sites and is anticipated to begin by June 2009 in the Australia and New Zealand clinical sites. Enrollment is expected to be complete within nine to 12 months.

 

Dr. Iwaki continued, "We look forward to building upon the encouraging data currently available for MN-221 by evaluating the compound in this planned larger, placebo-controlled clinical trial, which will work toward advancing our objective of developing MN-221 for treatment of severe acute exacerbations of asthma in our market territory."

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Tranzyme Pharma Announces Positive Phase 2 Results with TZP-101 for Improvement of Symptoms in Patients with Gastroparesis

Tranzyme Pharma today announced that its first-in-class, potent and selective ghrelin agonist, TZP-101, demonstrated effectiveness in the treatment of gastroparesis, an inability of the stomach to empty food efficiently, especially in patients with diabetes mellitus (DM). Clinical trial results indicated that TZP-101 was safe and highly effective in improving multiple symptoms associated with gastroparesis.

A total of 76 patients with either type 1 or type 2 DM and a confirmed diagnosis of gastroparesis (by presence of both chronic symptoms and objective demonstration of delayed gastric emptying) were enrolled in a US and EU, double-blind, placebo-controlled Phase 2 trial designed to evaluate the safety and efficacy of TZP-101. Patients were voluntarily admitted to the hospital and adaptively randomized to receive a daily 30-min IV infusion of one of six doses of TZP-101 (20-600g/kg) or placebo for 4 consecutive days. Overall, 57 subjects received TZP-101 and 19 received placebo. Patient safety was monitored by vital signs, ECGs, physical exams, clinical chemistry and adverse events.

During treatment and at a 30-day follow-up visit, efficacy was evaluated by symptom improvement as assessed by both the patients and the investigators. The Gastroparesis Cardinal Symptom Index (GCSI), a questionnaire for assessing the severity of symptoms associated with gastroparesis, was administered to each subject prior to dosing, on each of the treatment days and at the follow-up visit. Additionally, meal-related Gastroparesis Symptom Assessment (GSA) and Clinician Rated Symptom Assessment (CRSA) scores were collected for the study.

Summary Results: 80g/kg was determined to be the TZP-101 dose which achieved maximum clinical benefit. Upon completion of the 4-day dosing period, improvement in symptoms in TZP-101-treated subjects was statistically significant (or trending toward significance) over placebo-treated subjects as determined by one or more of the evaluation tools (GCSI, GSA, CRSA) for the following symptoms: vomiting (p=0.006), loss of appetite (p=0.034), postprandial fullness (p=0.007), early satiety (p=0.087), abdominal distension (p=0.053) and bloating (p=0.0822). Statistical significance was also observed by the CRSA Overall Symptom scores (p=0.046). The 30-day follow-up evaluation demonstrated a sustained benefit in symptom improvement in the TZP-101 group. This effect reached statistical significance (p=0.023) for vomiting, a particularly debilitating complication of gastroparesis. In addition, proportionally fewer subjects (3%) in the TZP-101 group required hospitalization for gastroparesis during the 30-day follow-up period versus the placebo group (10%). TZP-101 was safe and well-tolerated at all doses tested.

"We are encouraged to see that TZP-101, given intravenously for only 4 days, induced an acute and sustained reduction of symptoms offering a potential new therapy for patients with gastroparesis and other GI motility disorders in acute settings," said Gordana Kosutic, MD, Vice President, Clinical and Regulatory Affairs for Tranzyme. "These results are consistent with the potent prokinetic properties of TZP-101 and complement our previously reported successful Phase 2 study with TZP-101 for the management of postoperative ileus (POI)."

"We recognize the severity of symptoms caused by gastroparesis and their impact on quality of life, and are anxious to bring relief to the millions of patients suffering from this condition. We now plan to initiate a Phase 3 program to further evaluate the efficacy and safety of TZP-101 in this patient population," stated Vipin K. Garg, PhD, President and CEO of Tranzyme.

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Clavis Pharma ASA (OSE: CLAVIS) presented results from its elacytarabine Phase I combination study in patients with acute myeloid leukaemia (AML) at the American Association of Cancer Research (AACR) 100th Annual Meeting 2009 in Denver, USA. The poster pre

Clavis Pharma ASA (OSE: CLAVIS) presented results from its elacytarabine Phase I combination study in patients with acute myeloid leukaemia (AML) at the American Association of Cancer Research (AACR) 100th Annual Meeting 2009 in Denver, USA. The poster presentation was held on 21 April 2009.

 

Elacytarabine is a novel cytotoxic agent, and is an analogue of cytarabine - the backbone of therapy in acute leukaemia. Unfortunately a substantial portion of AML patients have a deficient uptake of cytarabine in their leukaemic cells due to deficient expression of a necessary transport protein, hENT1 (human equilibrative nucleoside transporter 1) on the cell membrane[1]. Cellular uptake of elacytarabine in contrast to cytarabine is independent of hENT1, which offers a potential clinical advantage to elacytarabine in the treatment of AML.

 

In the Phase I study elacytarabine was given in combination with idarubicin, an anti-leukaemia drug commonly used in combination with cytarabine. Elacytarabine was given at doses 1000 and 1150 mg/m2/day to 15 patients with AML. The maximum tolerated dose was 1150 mg/m2/day when administered as continuous infusion for 5 days in combination with a fixed dose of idarubicin, 12 mg/m2/d, given days 2 to 4. Toxicity was manageable and the dose limiting toxicities were typhlitis and hand-foot-syndrome. The recommended Phase II dose was determined to be 1000 mg/m2/d. Clinical activity was observed and four of 10 patients treated at the recommended Phase II dose were reported with complete remissions (CR/CRp).

 

Following the positive Phase I data, a Phase II combination study is in preparation in patients with early stage AML who have failed a first course of cytarabine based therapy. This is a patient group with an unfavourable prognosis for whom better therapeutic alternatives are needed. The purpose is to study response rates (CR CRp) to the combination therapy and the relationship of the response rate to the patient's nucleoside transporter (hENT1) status. The objective is to demonstrate that the efficacy of elacytarabine is independent of the patient's hENT1 status. The study will involve approximately 10 major cancer centres in the USA and Europe.

 

"The results presented at AACR from our first Phase I combination study in AML are most encouraging." says Geir Christian Melen, CEO of Clavis Pharma. "We are looking forward to continue with a Phase II study in first course failure patients where efficacy of elacytarabine in combination with idarubicin will be further evaluated. This program complements very well our ongoing elacytarabine single agent program in late stage AML patients where we recently released positive Phase II interim data".

 

The centres recruiting in the Phase I were MD Anderson Cancer Center (MDACC), Houston, Duke University Hospital, Durham, and University of Texas Health Science Centre (UTHSC) at San Antonio, all in the USA. Elacytarabine has previously been granted orphan drug designation by both the FDA and the European Commission for the treatment of AML. Elacytarabine is proposed by the World Health Organization as the international non-proprietary name [pINN] for CP-4055. The proposal is supported by the United States Adopted Name Council.

 

[1] Hubeek et al, Br J Cancer 2005 and Galmarini et al, Leukemia Research, 2002

 

Contact: Geir Christian Melen Chief Executive Officer Office : 47 24 11 09 50 Mobile : 47 91 30 29 65 E-mail : geir.christian.melen@clavispharma.com

 

Gunnar Manum Chief Financial Officer Office : 47 24 11 09 71 Mobile : 47 95 17 91 90 E-mail : gunnar.manum@clavispharma.com

 

About Elacytarabine and nucleoside transporter (hENT1) Clavis Pharma's lead product candidate elacytarabine (CP-4055) is a patented Lipid Vector Technology (LVT) version of the gold standard leukaemia drug, cytarabine. Elacytarabine has in clinical Phase I studies shown activity in haematological malignancies and a variety of solid tumours, and has shown superior activity over the parent drug cytarabine in many different preclinical tumour models. One important characteristic of elacytarabine is its independence of a certain cellular uptake mechanism (a specific nucleoside transporter, hENT1) whereas cytarabine is dependent on this transporter for entry into the cell. Many patients have low expression levels of this specific cellular uptake mechanism and a low level is known to be associated with poor outcome of treatment of AML with cytarabine (Hubeek et al, Br J Cancer 2005 and Galmarini et al, Leukemia Research, 2002).

 

About Leukaemia Approximately 300,000 new cases of leukaemia are diagnosed globally each year, resulting in around 220,000 deaths. Leukaemia represents a market with high unmet medical needs, which may open for accelerated approval processes to expedite market access for new drugs. It is a segmented market covering a broad variety of disorders. A major clinical concern is the high rate of disease recurrence. The five-year survival for the most common acute leukaemia type, acute myeloid leukaemia (AML), is in the range of 5-10% for treated elderly patients, and approximately 30% for treated younger adults.

 

About Clavis Pharma Clavis Pharma ASA is an oncology focused pharmaceutical company using its proprietary Lipid Vector Technology (LVT) platform to create New Chemical Entities (NCEs), by significantly improving already established drugs. The improvements are achieved by chemically binding specific unsaturated lipids to existing, and well understood, approved pharmaceuticals. Data generated suggests the resulting patentable NCEs offer improved efficacy and reduced side effects through enhanced pharmacokinetic properties, greater tissue penetration and, in many cases, additional modes of action.

 

Clavis Pharma's objective is to develop its drug candidates until significant value has been created and proof of principle in man has been shown. For further clinical development and commercialisation of the products, Clavis Pharma will enter into strategic partnerships with established pharmaceutical or biotech companies. The company's product portfolio includes four new cancer drugs: Elacytarabine[pINN] is in Clinical Phase II, Intravenous CP-4126 is in Clinical Phase II, Oral CP-4126 in Phase I, and CP-4200 is in early preclinical development. Results indicate that these products have promising potential for several cancer indications within solid tumours and leukaemia.

 

The shares of Clavis Pharma ASA are listed on the Oslo Stock Exchange (ticker: CLAVIS).

 

Disclaimer The information contained herein shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of the securities referred to herein in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration, exemption from registration or qualification under the securities laws of any such jurisdiction.

 

This news release contains forward-looking statements and forecasts based on uncertainty, since they relate to events and depend on circumstances that will occur in the future and which, by their nature, will have an impact on results of operations and the financial condition of Clavis Pharma. There are a number of factors that could cause actual results and developments to differ materially from those expressed or implied by these forward-looking statements. Theses factors include, among other things, risks associated with technological development, the risk that research & development will not yield new products that achieve commercial success, the impact of competition, the ability to close viable and profitable business deals, the risk of non-approval of patents not yet granted and difficulties of obtaining relevant governmental approvals for new products.

 

No expressed or implied representations or warranties are given concerning Clavis Pharma or the accuracy or completeness of the information or projections provided herein, and no claims shall be made by the recipient hereof by virtue of this Information Memorandum or the information or projections contained herein. Any representations or warranties made to an investor in Clavis Pharma will be subject to separate sale and purchase agreements to be negotiated between the parties.

 

Clavis Pharma(TM) is a registered trademark of Clavis Pharma ASA.

 

This announcement was originally distributed by Hugin. The issuer is solely responsible for the content of this announcement.

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Lexicon to Provide Clinical Pipeline Update and Report First Quarter 2009 Financial Results on April 28, 2009

Lexicon Pharmaceuticals, Inc. (Nasdaq:  LXRX) will release its first quarter 2009 financial results on Tuesday, April 28, 2009 before the financial markets open. Lexicon management will hold a conference call to discuss its clinical development progress and financial results for first quarter 2009 at 11:00 a.m. Eastern Time on April 28, 2009.

 

The dial-in number for the conference call is 888-220-1244 (within the US/Canada) or 706-679-5615 (international). The conference ID for all callers is 95206081. Investors can access a live webcast of the call at www.lexpharma.com. An archived version of the webcast will be available on the website through May 5, 2009.

 

About Lexicon

 

Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease. Lexicon currently has five drug candidates in development for autoimmune disease, carcinoid syndrome, diabetes, glaucoma and irritable bowel syndrome, all of which were discovered by Lexicon's research team. Lexicon has used its proprietary gene knockout technology to identify more than 100 promising drug targets. Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs. For additional information about Lexicon and its programs, please visit www.lexpharma.com.

 

Safe Harbor Statement

 

This press release contains "forward-looking statements," including statements relating to Lexicon's growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors that may cause Lexicon's actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under "Factors Affecting Forward-Looking Statements" and "Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2008, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

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Infinity Presents New Preclinical Data From Its Heat Shock Protein 90 Inhibitor Program At AACR

Infinity Pharmaceuticals, Inc. (Nasdaq:INFI) today presented data from its heat shock protein 90 (Hsp90) inhibitor program that supports the scientific rationale for Infinity's recently initiated Phase 2 study in breast cancer, and further enhances Infinity's scientific leadership in the field of Hsp90 inhibition. The data were presented during the 2009 American Association of Cancer Research (AACR) Annual Meeting in Denver. Infinity is developing two Hsp90 inhibitors: IPI-504, which is in Phase 2 clinical development, and its oral Hsp90 inhibitor, IPI-493, which is in Phase 1 clinical development.

 

Over-expression of the protein HER2 predicts an aggressive type of breast cancer for which Herceptin(r) (trastuzumab) is a primary treatment. Many patients, however, eventually develop resistance to Herceptin. In preclinical experiments, Infinity has shown that administration of IPI-504 results in the rapid degradation of HER2 in vitro, ultimately resulting in tumor cell growth inhibition and cell death. Preclinical data presented at AACR, in collaboration with researchers from Vall d'Hebron Institute of Oncology in Barcelona, Spain, now show that in Herceptin-resistant xenografts, HER2 protein levels were significantly reduced in vivo 12 hours after a single dose of IPI-504, and remained suppressed at 48 hours. Further, dose administration with IPI-504 in this model produced substantial tumor growth inhibition. In March 2009, Infinity initiated an open-label, international, multi-center Phase 2 clinical trial of IPI-504 in combination with Herceptin in patients with advanced or metastatic HER2-positive breast cancer.

 

Infinity presented additional preclinical data supporting the potential of its Hsp90 inhibitors in multiple cancer indications. In a presentation during AACR, Infinity reported that the in vivo anti-proliferative activity of its Hsp90 inhibitors is independent of the enzyme NQO1. Early work in Hsp90 inhibition had suggested that the presence of the enzyme NQO1 in cancer cells might be required in order for IPI-504 to have potent anti-tumor activity. Infinity showed that in a panel of 30 cancer cell lines, there is a poor correlation between levels of the enzyme NQO1 and the growth inhibitory activity of IPI-504. Furthermore, Infinity showed that cell lines that are not sensitive to IPI-504 in tissue culture are sensitive to IPI-504 when grown as mouse xenograft tumors in vivo. These data support the continued evaluation of Infinity's Hsp90 inhibitors in a broad range of cancers marked by low NQO1 expression.

 

Infinity researchers also reported on the development of a novel pharmacodynamic activity assay that quantifies Hsp90 inhibition in tumor samples. In preclinical animal models, IPI-504 and IPI-493 are rapidly cleared from the circulation and normal tissue, but accumulate in tumor tissue. Standard pharmacokinetic measurements used to monitor the levels of Hsp90 inhibitors in the clinic may not, therefore, represent an accurate assessment of the level of target inhibition in tumor tissue. Using the novel pharmacodynamic activity assay, tissue culture experiments demonstrated a correlation between the occupancy of Hsp90 and growth inhibition by IPI-504, confirming that IPI-504 affects cell growth through inhibition of Hsp90. Further, results from xenograft tumor samples taken from mice treated with IPI-504 in vivo showed that Hsp90 occupancy was better correlated with Hsp90 client protein degradation and efficacy than either plasma or tumor pharmacokinetics. Infinity plans to use its novel pharmacodynamic assay to directly measure Hsp90 inhibition in tumors and further evaluate the mechanism of action of its proprietary Hsp90 inhibitors, IPI-504 and IPI-493.

 

Hsp90 Inhibitor Program Clinical Development

 

Infinity is pursuing clinical development with its Hsp90 inhibitor product candidates, IPI-504 (i.v.) and IPI-493 (oral) in multiple indications. IPI-504 is being evaluated in a Phase 2 trial in combination with Herceptin(r) in patients with HER2-positive breast cancer, in the Phase 2 portion of a trial as a single agent in patients with advanced non-small cell lung cancer (NSCLC), and in a Phase 1 trial in combination with Taxotere(r) (docetaxel) in patients with advanced solid tumors. Infinity expects to report data from the Phase 2 study in patients with NSCLC and preliminary data from the Phase 1 combination study with Taxotere at the 2009 Annual Society of Clinical Oncology (ASCO) Annual Meeting. Infinity is also undertaking a Phase 1 clinical trial with IPI-493, its oral Hsp90 inhibitor, in patients with advanced solid tumors.

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Anergis SA Announces Successful Results of a Phase I/IIA Clinical Trial with Subcutaneous AllerT, its Novel Product for Desensitization of Patients Allergic to Birch Pollen

Anergis SA, a clinical-stage biopharmaceutical company developing innovative specific immunotherapy against allergies, today announced successful results of the proof-of-concept Phase I/IIA study AN003 with AllerT, its novel product, based on the Contiguous Overlapping Peptides (COP) technology, for desensitization of patients allergic to birch pollen.

 

"This new double-blind, randomized, placebo-controlled study with AllerT provides very encouraging results, which are fully consistent with our earlier experience with a COP product against bee venom allergies. In this new study involving twenty patients (placebo N=5 and AllerT N=15), safety was the primary endpoint: AllerT was well tolerated and safe in patients allergic to birch pollen and no patient experienced immediate allergic reactions, even though we administered doses equivalent to approximately ten times the maximal dose injected during conventional desensitization protocols" said Christophe Reymond, Ph.D., CSO of Anergis. "Importantly, with our secondary endpoints, we could also show marked and unequivocal immunological responses in patients treated with AllerT which are consistent with the induction of tolerance against birch pollen" added Dr Reymond.

 

"The results of this new study with AllerT provide further evidence supporting the concept of developing Contiguous Overlapping Peptides for the specific immunotherapy of patients with allergies;" said Vincent Charlon, Ph.D., CEO of Anergis, "COPs are safe, well-tolerated and immunogenic.  We want now to progress AllerT to the next development step, namely to conduct a large-scale Phase II clinical trial with adequate statistical power to demonstrate clinical efficacy, i.e. desensitization of patients allergic to birch pollen" 

 

Professor François Spertini, M.D., principal investigator of the trial commented "Every year we see numerous patients suffering from birch pollen allergies.  We recommend specific immunotherapy to only very few of them because these treatments, whether given subcutaneously or via the sublingual route, require a 3 to 5 years commitment of the patient and are not devoid of risks of serious anaphylactic reactions. With AllerT, we can administer high doses of the allergen safely within a very short period, we have shown marked immunological responses in these patients, and we hope to show soon the induction of clinical tolerance in further seasonal studies.  A fast and safe desensitization option would certainly be highly attractive to many of our patients."

 

About AllerT: AllerT is a proprietary product of Anergis SA, currently in clinical development for the specific immunotherapy of patients with moderate to severe allergies to birch pollen.  Birch pollen allergies are common in the northern hemisphere, affecting 90% of patients allergic to tree pollens.  AllerT is composed of a set of peptides derived from the major birch pollen allergen Bet v 1. These peptides together contain all T cell epitopes of Bet v 1 but have been designed by Anergis (COP technology) to present no cross-reactivity with Bet v 1 specific IgEs.  AllerT has been tested in vitro, in animals and in an earlier clinical trial, all showing markedly reduced or absence of IgE-mediated immediate allergic responses.

 

About Study AN003: Study AN003 was the first clinical trial with repeated administrations of AllerT to patients allergic to birch pollen. This was a double-blind, randomized, placebo-controlled, single-centre study conducted at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland by François Spertini, M.D. Volunteers were screened for their reactivity to birch pollen and randomized to receive either AllerT or placebo.  The study was designed to include two consecutive cohorts of 20 patients each: subcutaneous injections cohort (AllerT N=15, placebo N=5) and intra-dermal injections cohort (AllerT N=15, placebo N=5).  The second cohort treated with intra-dermal injections is still ongoing and has not yet been analyzed.  The primary objectives of the study were to evaluate the safety and tolerability of AllerT, administered on days 1, 7, 14, 21 and 51 of the study.  Adverse events were collected as solicited and non-solicited events for 4 days after each injection and collected throughout the study up to one month after the last injection.  Blood was collected for analysis of immunological markers (Bet v 1 specific IgG4, Bet v 1 specific IgE, in vitro T cell proliferation, T cell cytokine profile) prior to the injection on days 7, 14, 21, 51 and 85. Nasal provocation tests with birch pollen were performed using stepwise pollen dose increase at screening and on day 85 of the study. These latter tests were inconclusive due to the very limited number of patients. All patients completed the study: no subject was either withdrawn from the trial prematurely or lost to follow-up. This clinical study is supported by a CTI grant from the Swiss OFFT (Office Federal de la formation et de la technologie).

 

François Spertini, M.D. is Associate Professor at the University of Lausanne, Division of Immunology and Allergy, Switzerland. Prof Spertini is the inventor of the technology of Contiguous Overlapping Peptides and the founder of Anergis SA to whom all rights to the technology have been transferred in 2005.

 

About Anergis SA: Anergis SA is a Swiss-based biopharmaceutical company specializing in the discovery and development of novel specific immunotherapy (also known as "SIT" or "desensitization") products. Allergy is the most prevalent and the fastest growing chronic condition in the industrialized world with over 300 million people affected. Current SIT remains underused due to its long duration (3-5 years of treatment) and safety risks. Anergis' objective is to make SIT treatments available to many more allergic patients than today, by providing novel safe and fast desensitization products. Anergis possesses a unique know-how and an exclusive license to the technology of Contiguous Overlapping Peptides ("COPs") developed jointly by the University of Lausanne, Switzerland (UNIL), the Federal Institute of Technology (EPFL) and the Centre Hospitalier Universitaire Vaudois (CHUV). The technology of COPs allows the identification and development of uniquely profiled proprietary products intended for ultra-fast and safe desensitization. In the past years, Anergis has already identified and studied proprietary COPs targeting bee venom and birch pollen allergies, both in animals and in humans. These studies have clearly established the safety, tolerability and immunogenicity of the COP technology.

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NovaBay(R) Pharmaceuticals Enters into Agreement to Broaden Intellectual Property Estate and Expand Clinical Opportunities for Its Aganocide(R) Compounds

NovaBay Pharmaceuticals, Inc. (NYSE Amex:  NBY), a mid-stage biopharmaceutical company developing first-in-class, potent, well-tolerated products to treat and prevent a wide range of infections with low chance of developing drug resistance, today announced an exclusive agreement with Professors Markus Nagl M.D. and Waldemar Gottardi, Ph.D. of the Medical University of Innsbruck, Austria. The agreement was entered into to advance the development of NovaBay's Aganocide compounds by integrating extensive and on-going clinical work at the university with NovaBay's development program.

 

Professors Gottardi and Nagl have conducted extensive clinical research and have patented and published widely for many years on the use of N-chlorotaurine (NCT), a natural antimicrobial produced by the body's white blood cells. NovaBay's Aganocide compounds are synthetic analogs of NCT that maintain or enhance the biological activity of the natural compound while adding pharmaceutically acceptable stability. Professors Gottardi and Nagl have pioneered the exploratory use of NCT compounds in humans in a number of indications that overlap with and even go beyond those for which NovaBay's Aganocide compounds are currently being developed.

 

Under the terms of the agreement, NovaBay will fund ongoing research in the laboratories of Professors Gottardi and Nagl at the Medical University of Innsbruck and NovaBay will have access to past and future data generated in human clinical trials by Professors Nagl, Gottardi and their collaborators. These data are expected to support many of the indications being pursued by NovaBay and its partners. For instance, they have published successful results of a Phase II clinical trial in ear infections (otitis externa) using NCT. NovaBay expects Alcon, its licensee for the use of Aganocide compounds in the treatment of eye, ear, and sinus infections, to start human trials in the ear during 2009 with NovaBay's lead Aganocide compound NVC-422. Professors Nagl and Gottardi have also pursued studies with NCT in additional indications that can provide NovaBay with guidance in its future clinical programs.

 

In addition to the research agreement, NovaBay has obtained an exclusive license to a broad portfolio of intellectual property covering uses of NCT compounds. As a result, NovaBay has augmented its composition of matter patent for Aganocide compounds with a license to a series of patents covering key potential uses, including utility of NCT compounds in pulmonary diseases and their potential use in major animal health markets, such as mastititis.

 

"We are very excited to collaborate with this world-class research team, and pleased to draw on the extensive experience of Professors Gottardi and Nagl in understanding the role of our class of molecules in the prevention and treatment of infectious diseases," said Dr. Ron Najafi, Chairman and Chief Executive Officer of NovaBay. "We look forward to building on their work to further expand the range of clinical opportunities provided by our Aganocide compound platform."

 

"We expect to substantially broaden NovaBay's efforts by leveraging the resources and expertise at the Medical University of Innsbruck," said Dr. Bez Khosrovi, Vice President of Research and Development at NovaBay. "We see this collaboration as adding significant depth to our preclinical and clinical development programs and to the continued exploration of the properties of our Aganocide compounds. We expect that our joint efforts will provide important information that may further accelerate our efforts to develop this novel class of anti-infectives."

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PPD stock tumbles over cancellations

PPD Inc. shares plunged Wednesday morning after the company lowered its 2009 guidance in the wake of $215 million in contract cancellations and adjustments during the first quarter.

 

The Wilmington, N.C.-based contract research organization, which has about 1,200 employees in Austin, lowered its 2009 revenue estimate to a range of $1.395 billion to $1.47 billion from previous guidance of revenue between $1.595 billion and $1.67 billion. Analysts polled by Thomson Reuters had been projecting, on average, annual revenue of about $1.6 billion.

 

In announcing its quarterly earnings, PPD (Nasdaq: PPDI) revealed that a large biotech client had canceled a $76.9 million multinational clinical trial. PPD did not release the name of the company.

 

PPD shares were down 16.14 percent, to $18.44, in mid-morning trading.

 

The company's first-quarter results were mixed. Net revenue fell, to $364.9 million from $392.5 million. Net income grew, to $44.56 million from $40.1 million, though the first quarter 2008 number was reduced by a $16 million investment loss. On a per-share basis, diluted earnings were 38 cents, up from 33 cents.

 

"While net revenue was below expectations for the quarter, PPD generated strong earnings and solid cash flow," CEO Fred Eshelman said.

 

PPD also announced Wednesday that it completed its acquisition of AbC.R.O., a clinical research organization operating in central and eastern Europe and that it has opened an office in Tokyo to expand its phase II-IV clinical development services in east Asia.

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FDA Gives Clinical Trial Green Light on Drug to Treat Alzheimer's Disease

The Food and Drug Administration (FDA) has given the Blanchette Rockefeller Neurosciences Institute (BRNI) the go-ahead to conduct Phase II clinical trials of Bryostatin for the treatment of Alzheimer's disease patients. The drug showed pre-clinical efficacy to not only treat Alzheimer's disease symptoms, but also its underlying causes.

 

"We are very excited about the FDA's agreement for BRNI to move forward with clinical trials," said Dr. Daniel Alkon, Scientific Director of BRNI. "Bryostatin shows the promise to repair and protect against neurodegeneration caused by Alzheimer's disease, stroke and other brain trauma, as well as enhance the brain's normal memory functions."

 

Bryostatin was originally created as an anti-cancer chemotherapy. When BRNI scientists extensively tested PKC activators against Alzheimer's disease models, they discovered the drug's hidden potential to stop Alzheimer's disease. Over the past six years, the drug has shown remarkable possibilities. In preclinical testing, BRNI scientists experimented with Bryostatin on three species of Alzheimer's disease transgenic mice, each species based on different human Alzheimer's disease genes. The test results revealed that Bryostatin, and a related class of drugs discovered at BRNI, can reduce the toxic Alzheimer's disease protein A Beta, restore lost synapses, and protect against the loss of memory functions. In related preclinical testing, Bryostatin has been shown to enhance and restore memory by rewiring connections in the brain previously destroyed by stroke, head trauma, or aging itself.

 

The Phase II trials, slated to begin in approximately two to four months, will test these preclinical findings on human Alzheimer's disease patients as well as controls, along with Bryostation's effects on molecular targets in the human body, such as the signaling enzyme PKC. The drug's side effects will also be carefully monitored using low doses that were previously found to be generally benign in human cancer patients.

 

"With the potential to not just treat symptoms, but also stop the causes, the Bryostatin trial on Alzheimer's disease patients represents a new direction for the treatment of a disease with no current cure," said Alkon. "And the timing is crucial because as many as 5.3 million people live with Alzheimer's disease in the United States alone, with a new American developing Alzheimer's disease every 70 seconds."

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BioMarin initiates Phase I/II lysosomal storage disorder trial

BioMarin Pharmaceutical has initiated a Phase I/II clinical trial for BMN-110 or N-acetylgalactosamine 6-sulfatase, intended for the treatment of the lysosomal storage disorder mucopolysaccharidosis type IVA, or Morquio A syndrome.

 

The Phase I/II study is designed as an open-label, within-patient dose escalation trial in approximately 20 patients followed by a treatment continuation phase. All patients to be enrolled in the study have already been identified. During the dose escalation phase of the study, subjects will receive weekly intravenous infusions of BMN-110 in three consecutive 12-week dosing intervals.

 

The objectives of the Phase I/II study will be to evaluate safety, pharmacokinetics, pharmacodynamics and to identify the optimal dose of N-acetylgalactosamine 6-sulfatase (GALNS) for future studies. The company expects to report initial results in the first half of 2010.

 

Henry Fuchs, chief medical officer of BioMarin, said: "GALNS has been shown in mice to reach important tissues including cartilage and different zones of the bone such as bone marrow, calcified bone and importantly, the growth plate. Our experiments have also shown that GALNS is taken up into human Morquio chondrocytes in vitro and reaches the lysosome to clear keratan sulfate."

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Fulvestrant-Chemo Combo Targeted for ER Positive Breast Cancer

Researchers from The Cancer Institute of New Jersey (CINJ) are converging on Denver for the 100th Annual Meeting of the American Association for Cancer Research (AACR) to share their findings on a combined treatment targeting breast cancer that is stimulated by the hormone estrogen (estrogen receptive positive). They are joining other top investigators from around the globe for the event, which is highlighting interdisciplinary approaches to cancer research. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.

 

Among the abstracts being presented is one focusing on how the FDA-approved therapy fulvestrant can influence the effects of chemotherapy drugs on breast cancer cells. Fulvestrant is commonly used in postmenopausal women to treat estrogen receptive positive breast cancer that has spread to other parts of the body.

 

Breast cancers that respond to female hormones, such as estrogen, generate specific proteins that help tumor cells survive and grow. One such protein, HDM2, is known to be present in higher levels in many cancers including breast. These higher protein levels are strongly correlated with the presence of the estrogen receptor on breast cancer cells, which can affect how well chemotherapy works. Targeting the receptor is a common treatment for breast cancer.

 

Lead author Adriana V. Jager, PhD, a postdoctoral fellow at CINJ, and her colleagues focused on adding fulvestrant to the traditional chemotherapy agents doxorubicin, etoposide and paclitaxel, as fulvestrant is known to degrade the estrogen receptor and result in less stimulation of tumor cell growth. They found that in two estrogen receptor positive breast cancer cell lines, fulvestrant decreased HDM2 levels and enhanced the sensitivity of these cells to chemotherapy. This enhancement was better than either fulvestrant or chemotherapy alone.

 

According to the American Cancer Society, 183,000 cases of breast cancer were diagnosed nationwide last year, with 6,300 new cases in New Jersey alone. With such statistics, the team is hopeful that this laboratory-based research can be expanded to a clinical trial with patients in order to further explore improved outcomes.

 

The author team also includes William N. Hait, MD, PhD, Johnson and Johnson/Centocor; Deborah Toppmeyer, MD, CINJ; Bruce G. Haffty, MD, CINJ; Kim Hirshfield, MD, PhD, CINJ; and Jin-Ming Yang, PhD, Penn State.

 

The work represented by CINJ members is among the 6,000 abstracts being presented at the gathering, which is featuring more than 17,000 researchers, healthcare professionals, and patient advocates. The goal of the annual AACR event is to provide a forum in which the latest in cutting-edge laboratory, clinical and translational research can be shared.

 

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Elusys' Anthrax Anti-Toxin, Anthim(TM), Enters Second Phase I Clinical Study

Anthim Dramatically Improves Survival in Animals with Clinical Symptoms of Anthrax disease -

 

Elusys Therapeutics, Inc. (Elusys), a privately-held biopharmaceutical company developing antibody-based therapies for the treatment of life-threatening infectious diseases, today announced the initiation of a second Phase I human safety trial of Anthim(TM), a high-affinity humanized and deimmunized monoclonal antibody targeting the anthrax toxin protective antigen.

 

The Phase I dose-escalation trial is planned to enroll 45 healthy volunteers and is designed to expand the human safety database. Elizabeth Posillico, Ph.D., President and Chief Executive Officer of Elusys, commented, "We are extremely pleased with the success of our development program for Anthim. Our drug consistently demonstrates remarkable efficacy in treating anthrax infection in animal models and is a strong candidate for addition to the Strategic National Stockpile."

 

The Company also reported the results of a previously conducted animal efficacy study. A single dose of Anthim provided a significant survival benefit (up to 94 percent survival in treated rabbits vs. 0 percent in controls) when administered to symptomatic rabbits. These results are consistent with several previous rabbit and primate studies that Elusys has conducted and show the dramatic protective effect of Anthim. Dr. Leslie Casey, Vice President of Research, commented, "Anthim has shown significant life-saving potential even when given in a single dose to symptomatic animals many hours after anthrax exposure. In earlier animal studies, Anthim provided 100 percent protection when given within 12 hours of an anthrax exposure. These results have been consistent across studies whether Anthim was used with or without antibiotics. Our first Phase I human safety study demonstrated that Anthim is safe and well-tolerated as a monotherapy and as a combined therapy with the antibiotic ciprofloxacin. This second study will continue to expand our safety database and provide additional pharmacokinetic data."

 

Dr. Posillico added, "Death from the effects of anthrax toxin can occur in a few days if patients are not treated quickly. We are very excited about Anthim because the results of all of our studies show that treatment with Anthim has the potential to provide significant therapeutic benefit for people infected with anthrax in a bioterrorism emergency." Currently antibiotics represent the only therapeutic option for anthrax infection. Antibiotics target the bacteria, but can still fail to prevent death from the damaging effects of anthrax toxins. In addition, antibiotic resistant strains of anthrax could be used in a bioterror attack, making the medical need for anti-toxin therapy even more acute.

 

Anthim Background

 

Anthim is a high-affinity, humanized and deimmunized monoclonal antibody that targets the protective antigen of B. anthracis and neutralizes the lethal effects of anthrax toxins. It is being developed for prevention and treatment of inhalation anthrax. Anthim has been granted Fast-Track status and Orphan Drug Designation by the FDA. The National Institutes of Health and the Department of Defense have awarded Elusys a total of $34 million for the development of Anthim, of which $12 million was awarded in September 2007 under contract #HHSN272200700035 from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the Biomedical Advanced Research and Development Authority (BARDA), part of the Department of Health and Human Services. In April of 2007, Anthim was selected to R&D Directions' list of "100 Great Investigational Drugs."

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Poniard Pharmaceuticals Presents Final Results of Phase 1 Study of Picoplatin in Patients with Metastatic Colorectal Cancer

Safety and Tumor Response Data from Dose-Escalation Study Presented at

 

American Association for Cancer Research's 100th Annual Meeting 2009 -

 

Poniard Pharmaceuticals, Inc. (Nasdaq: PARD), a biopharmaceutical company focused on oncology, today announced the presentation of final data from a Phase 1 dose-escalation study of picoplatin in patients with metastatic colorectal cancer (CRC). Results demonstrated that picoplatin can be safely administered in combination with 5-fluorouracil and leucovorin (FOLPI) as a first-line option for CRC. Based on the safety data as well as the promising clinical activity observed in this trial, Poniard initiated a randomized, controlled, proof-of-concept Phase 2 trial to evaluate picoplatin as a neuropathy-sparing alternative to oxaliplatin for the first-line treatment of metastatic CRC. Patient enrollment was completed in May 2008.

 

"Several treatment options for metastatic CRC have been introduced in the last decade and have resulted in enhanced survival when administered as a first-line treatment. However, these treatments can cause serious side effects, including severe neuropathies that prevent patients from participating in routine daily activities and may lead to discontinuing therapy," said Robert De Jager, M.D., chief medical officer of Poniard. "We are encouraged by these preliminary results, which continue to show that picoplatin given once every four weeks as part of the FOLPI regimen is associated with less frequent and severe neurotoxicity than oxaliplatin given in combination with 5-fluorouracil and leucovorin in the FOLFOX regimen; both regimens have similar anti-tumor activity in first-line metastatic CRC. We are continuing to observe the study participants and look forward to presenting initial progression-free survival data at the 2009 American Society of Clinical Oncology Annual Meeting."

 

The picoplatin data were presented today in a poster session (abstract #3578) during the American Association for Cancer Research's 100th Annual Meeting 2009 at the Colorado Convention Center in Denver. Picoplatin, the Company's lead product candidate, is a new generation platinum chemotherapy agent in clinical development to treat multiple types of cancer. It is designed to overcome platinum resistance associated with chemotherapy in solid tumors.

 

Phase 1 CRC Study Design and Results

 

In the Phase 1 study, 73 patients received the FOLPI regimen with picoplatin administered either every two or every four weeks to evaluate safety and identify the maximum tolerated dose and the optimal schedule of FOLPI administration. Patients received a total picoplatin exposure of between 85 mg/m squared and 1,871 mg/m squared.

 

None of the patients who received picoplatin exhibited severe neuropathy (Grade 3 or 4), as is commonly seen in metastatic CRC patients treated with the FOLFOX regimen at cumulative oxaliplatin doses above 800 mg/m squared. In addition, none of the patients who received picoplatin exhibited severe (Grade 3/4) nephrotoxicity (kidney toxicity) or ototoxicity (hearing toxicity).

 

The dose limiting toxicities for both the every-four-week regimen and the every-two-week regimen were neutropenia and thrombocytopenia, which were reversible. The maximum tolerated dose of picoplatin in the every-four-week FOLPI schedule was 150 mg/m squared. 150 mg/m squared for the every-four-week FOLPI schedule and 85 mg/m squared for the every-two-week FOLPI schedule achieved 80 percent of the planned dose and support further clinical studies at these doses and schedules. The 150 mg/m squared dose and schedule was selected for evaluation in the ongoing randomized Phase 2 trial.

 

Of 18 evaluable patients who received the every-four-week FOLPI regimen, 67 percent achieved disease control (partial response and stable disease). Of 55 evaluable patients who received the every-two-week FOLPI regimen, 75 percent achieved disease control.

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Circassia's Allergy Therapy Begins Phase II Clinical Trial in Asthma Patients

Circassia Ltd, a specialty biopharmaceutical company focused on allergy, announced today that it has initiated a phase II clinical study of its ToleroMune(R) technology in allergy patients with asthma. The trial builds on positive phase II results that demonstrated the potential clinical benefits of ToleroMune allergy therapy, and extends clinical investigations to those with allergy-associated asthma.

 

The lastest study, which is underway in Canada, will enrol 48 patients with confirmed cat allergies and cat-allergen induced asthma. The randomised, double-blind, placebo-controlled trial will study the use of a standard dose of ToleroMune administered over a number of weeks. This is in marked contrast to most current immunotherapy treatments, which require carefully escalated weekly dosing over many months, followed by further monthly doses for several years, to reduce the risk of potentially serious adverse reactions. During the study, each patient will receive a controlled 'challenge' with cat allergens, both before and after treatment, to allow investigators to assess the effect of ToleroMune therapy compared to placebo.

 

"This study marks an important milestone in the development of our ToleroMune anti-allergy technology, as it extends our target patient group to those with more serious allergies that can result in asthma attacks," said Steve Harris, Circassia's CEO. "We believe that Circassia's allergy therapies will offer patients important clinical benefits. Most existing treatments address either symptoms only, or require lengthy and complicated dosing because of their potential to lead to serious and even lifethreatening reactions. In contrast, our clinical results show that ToleroMune has the potential to treat the underlying causes of allergies, using short and simple courses of treatment that minimize the risk of severe side effects."

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Seattle Genetics Highlights Dacetuzumab Preclinical Research at AACR

Seattle Genetics, Inc. has announced preclinical data with dacetuzumab describing a diagnostic gene signature that may identify lymphoma patients who are more likely to respond to dacetuzumab therapy. In addition, data demonstrating the enhanced activity of dacetuzumab in combination with conventional chemotherapy agents were reported. The data were presented at the 2009 Annual Meeting of the American Association for Cancer Research (AACR) being held in Denver, CO.

 

"The gene signature research being conducted under our collaboration with Genentech suggests that there may be a diagnostic test that can predict which patients are most likely to benefit from dacetuzumab therapy, aiding in the development of this antibody and providing another step towards the promise of personalized medicine for lymphoma patients," said Clay B. Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics. "This work, combined with our extensive preclinical findings on the enhanced activity of dacetuzumab in combination with other agents, continues to inform and support our clinical development activities. We anticipate that our ongoing clinical trials of dacetuzumab in combination with standard therapeutic regimens will begin to yield data later in 2009."

 

Dacetuzumab is a humanized anti-CD40 monoclonal antibody being developed by Seattle Genetics and Genentech, Inc., a wholly-owned member of the Roche Group, under a worldwide license agreement. The companies are conducting a broad development plan consisting of five ongoing phase Ib-IIb clinical trials evaluating dacetuzumab in combination with standard regimens for patients with non-Hodgkin lymphoma or multiple myeloma.

 

The data reported at AACR show a correlation between a diagnostic gene signature and sensitivity to treatment with dacetuzumab in patients with diffuse large B-cell lymphoma (DLBCL). The gene signature, which was originally identified in non-Hodgkin lymphoma cell lines, was retrospectively analyzed in patient samples from completed single-agent clinical trials of dacetuzumab. Data demonstrate that the gene signature correlated with sensitivity to treatment with dacetuzumab and had an overall accuracy of 80 percent. Furthermore, patients who were positive for the gene signature experienced longer progression-free survival compared to patients who were not. This diagnostic gene signature is being evaluated in ongoing clinical trials of dacetuzumab in combination with standard chemotherapy (Abstract # LB-138).

 

In a separate presentation, data showed the synergistic activity of dacetuzumab in combination with conventional cytotoxic drugs commonly used in the treatment of lymphoma. In addition, dacetuzumab was shown to sensitize non-Hodgkin lymphoma tumors to Gemzar® (gemcitabine), and improve the efficacy of Rituxan® (rituximab) plus Gemzar in preclinical models of non-Hodgkin lymphoma (Abstract # 3243). A phase Ib clinical trial of dacetuzumab in combination with Rituxan and Gemzar for patients with relapsed or refractory DLBCL is ongoing.

 

Downloadable copies of Seattle Genetics' AACR posters are available from the "Technology" section of the company's website at www.seattlegenetics.com.

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Palau Pharma Initiates A Phase II Clinical Trial Of Dersalazine Sodium In Mild To Moderate Ulcerative Colitis

Palau Pharma, S.A. ("Palau"), the specialty pharmaceutical company focused on the discovery and development of novel products for the treatment of inflammatory and autoimmune diseases, today announces that the first patient has been enrolled in a Phase II clinical trial of dersalazine sodium, Palau's novel oral therapy for the treatment of mild to moderate ulcerative colitis (UC).

 

The study is a Phase II multi-centre, randomized, double blind, parallel group, two placebos and active reference controlled study of the safety and activity of dersalazine sodium when administered to patients with active, mild to moderate, UC. Eighty (80) subjects will be studied in three parallel groups (dersalazine sodium, mesalazine and placebo), with a randomization of 2:1:1. Each subject will receive doses of dersalazine sodium, placebo or mesalazine twice daily for 4 weeks. The study will be conducted in 4 European countries and in 16 investigational sites.

 

This study represents the first investigation of dersalazine sodium in UC patients and has been designed to obtain initial information on the safety, tolerability and activity of the product in patients before a full length treatment is given in a clinical setting.

 

A successful randomized, double-blind, placebo and active standard controlled Phase I study to assess the tolerability of raising multiple doses of dersalazine sodium in healthy volunteers was completed during 2008. This was designed to assess the safety and tolerability of four rising oral dose levels given twice daily during 14 days to healthy male subjects.

 

UC is a chronic, relapsing inflammatory disease that affects the colon. It is estimated to affect one in 1000 people in the Western world . Ulcerative colitis treatments aim to suppress the acute inflammatory process during the disease flare (acute treatment) and to limit the occurrence of new flares (maintenance treatment). Current therapies for mild and moderate disease rely mainly on aminosalicylates, but often efficacy is limited to short-term use. Resistant or more severe disease can be treated with corticosteroids, immunosuppresants or anti-TNF? agents. However, adverse effects, inconvenience and high cost limit their long-term use.

 

Dersalazine sodium is a new chemical entity that was designed by Palau's scientists as the result of linking a potent anti-TNF? agent (UR-12715) with 5-aminosalicylic acid (5-ASA) by an azo bond. Dersalazine sodium is carried unaltered through the upper gastrointestinal tract until azo-reduction by the colonic bacteria, initiating the release of both active compounds in the colon, where they act as topical anti-inflammatory agents. By linking UR-12715 with 5-ASA, the release of UR-12715 directly to the inflamed mucosa is enhanced and potential systemic effects are minimized. If proven clinically active and safe, dersalazine sodium may constitute a landmark in the treatment of UC.

 

"We are delighted to announce the enrollment of the first patient in this phase II trial. Dersalazine sodium has the potential to address the issues associated with the long term use of current ulcerative colitis treatments utilizing a new approach in the application of well profiled 5-aminosalicylic acid," commented Ignacio Faus, Chief Executive of Palau Pharma. "Following our strategy for this project, after completion of this study, we will seek a license partner for the further worldwide development and commercialization."

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Mersana's Second Development Candidate, XMT-1107, Shows Superior Pharmacokinetics and Anti-Tumor Activity in Studies Presented at American Association of Cancer Research Meeting

Mersana, a platform-based cancer therapeutics company, today announced positive results of preclinical studies for its second development candidate, XMT-1107, in two posters at the 2009 Annual Meeting of the American Association of Cancer Research (AACR) in Denver.

 

The studies showed that XMT-1107, a novel anti-angiogenic fumagillin analog conjugated to Mersana's proprietary Fleximer(R), demonstrated superior anti-tumor activity in tumor xenograft models in comparison to other anti-angiogenic agents and extended exposure to the conjugated drug, supporting the potential clinical utility of XMT-1107 as an anti-cancer agent. Full text of the abstracts can be viewed online at the AACR website at www.AACR.org.

 

"Anti-angiogenic and anti-tumor activity of XMT-1107, a fumagillin-derived polymer conjugate, and its in vivo release product XMT-1191"

By Laura C. Akullian, Cheri A. Stevenson, John Benson, Robert J. Fram, Timothy B. Lowinger

 

This study showed that XMT-1107 has enhanced anti-angiogenic and anti-tumor activity compared to small molecule analogs delivered without the benefit of Fleximer.

 

XMT-1107 inhibited human MetAP2 in vitro, was highly active in human umbilical vein endothelial cell (HUVEC) proliferation assays, and showed anti-angiogenesis activity in vivo in the Matrigel plug assay. Additionally, XMT-1107 was active in a number of syngeneic and xenograft tumor models. The enhanced antiangiogenic and in vivo anti-tumor activity of XMT-1107 compared to its in vivo release product XMT-1191 clearly demonstrated the benefit of conjugating XMT-1191 to Fleximer(R) and supports the potential clinical utility of XMT-1107 as an anti-cancer agent.

 

"Pharmacokinetics of a novel fumagillol conjugate XMT-1107 in the rat"

By Alex Yurkovetskiy, Dana L. Shkolny, Laura C. Akullian, Mao Yin, Laraine L. Meyers, Robert J. Fram, Timothy B. Lowinger.

 

This study evaluated the pharmacokinetics (PK) of XMT-1107 and its conjugate release product, XMT-1191, in rats. The XMT-1107 conjugate extended exposure to its corresponding drug release product, XMT-1191, while significantly reducing (> 500 fold) maximum XMT-1191 plasma levels (Cmax).

 

The data suggest that the slow rate of release of XMT-1191 from the polymer conjugate XMT-1107 provided a low but consistent exposure to the highly active XMT-1191 small molecule, providing an apparent half life of 22 hours compared with a half life of less than five minutes with free XMT-1191 administration. The data are consistent with the significantly higher in vivo activity seen for XMT-1107 relative to XMT-1191 in xenograft activity reported in a separate poster.

 

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Allos Therapeutics' Pralatrexate Demonstrates Anticancer Activity in Multiple Cancer Cell Lines

Allos Therapeutics, Inc. today announced new data demonstrating the anticancer activity of its investigational drug, pralatrexate, in colon, ovarian, lung, prostate, and head and neck cancer cell lines. The preclinical research further showed that the antiproliferative effects against these cancer lines were achieved at drug concentrations that are attainable in humans. These data were presented today at the American Association for Cancer Research (AACR) Annual Meeting in Denver, CO.

 

The results, outlined in a poster titled "Cytotoxicity of Pralatrexate, a Novel Synthetic Antifolate, in Human Cancer Cell Lines (abstract #1686)," demonstrate anticancer activity of pralatrexate in nine of 15 human cell lines tested. Importantly, it appears from analyses of exposure time that the effect of pralatrexate is reached rapidly, within 24-72 hours. During this window, cancer cells susceptible to pralatrexate undergo apoptosis, or cell death.

 

Further analysis of the data demonstrated a potential correlation between the sensitivity to pralatrexate and the expression level of folyl-polyglutamate synthetase (FPGS), an enzyme that catalyzes the addition of polyglutamate tails to folate derivatives such as pralatrexate. It is believed that the polyglutamation of pralatrexate by FPGS prevents cancer cells from excreting pralatrexate from the cell. The ability of cancer cells to excrete drugs through efflux pumps is a common drug resistance mechanism and has been a challenge in the development of antifolates. By remaining in the cancer cell for a longer period of time pralatraxate has an opportunity to increase tumor cell kill.

 

Further study is required, but FPGS may prove to be an important biomarker to predict cancer patients' sensitivities to pralatrexate.

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PAION Initiates Phase Ib Study of the Anesthetic/Sedative CNS 7056 in Volunteers Undergoing Colonoscopy

* Aim of trial is to study a variety of (repeat-) doses to achieve an overall 30 min sedation time
* Study also evaluates reversal of sedation with an established antagonist

 

The biopharmaceutical company PAION AG today announces the start of a Phase Ib multiple dose study with the new short-acting intravenous anesthetic/sedative CNS 7056 in volunteers undergoing colonoscopy.

 

The randomized, open, dose-escalation multiple dose Phase Ib study will evaluate the sedation and recovery profile of CNS 7056 in volunteers undergoing colonoscopy. In the first part of the study the reversal of sedation induced with CNS 7056 by the benzodiazepine antagonist, flumazenil, will be examined in a double-blind design. This approach is intended to provide further support for an important safety feature for the compound, i.e. the opportunity to reverse sedation when desired (e.g. in case of an inadvertent overdose). The first volunteers have been included in this part of the study.

 

In the subsequent open part of the trial volunteers will receive three different dosages of CNS 7056 followed by "top ups" (i.e. multiple dose) as required to maintain an adequate sedation level for 30 minutes whilst they undergo a standard colonoscopy procedure. The study is being performed in the US and is expected to complete before the end of 2009.

 

PAION last week also had started a single-dose Phase II study examining sedation of patients undergoing endoscopy of the upper gastrointestinal tract. The necessity of performing these two studies is based on the differing length of gastroscopy and colonoscopy interventions. The Phase Ib study with CNS 7056 will allow PAION to generate additional data on pharmacodynamics and pharmacokinetics.

 

"The results of these two studies will be the basis for the further development in procedural sedation. Performing a colonoscopy in a Phase I setting allows mimicking the clinical routine setting. Thus this study will deliver information usually generated in a Phase II study," commented Dr. Wolfgang Söhngen, PAION's CEO. "Our team has again demonstrated its strength in being able to achieve significant steps in the clinical development in a very focused and efficient way."

 

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Interventional Spine Announces the Initiation of Its U.S. Clinical Study for Percutaneous Treatment of Degenerative Disc Disease

Interventional Spine, Inc. announced today the successful completion of the first U.S. out-patient interventional procedure using its PDS System for the treatment of Degenerative Disc Disease (DDD) in the lumbar spine. This milestone marks the initiation of a clinical study pursuant to an Investigational Device Exemption protocol approved by the U.S. Food and Drug Administration in late November 2008.

 

"Our goal for this study is to prove the safety and effectiveness of the PDS System as an alternative in the treatment of chronic back pain related to DDD for many of the 400,000 patients annually facing open fusion lumbar surgery in the United States," said Walter A. Cuevas, Interventional Spine's CEO. "Presently, most fusion surgeries still require large open incisions across the primary muscle groups in the back, multi-day hospitalization, and extended rehabilitation. A very different future for DDD back pain patients was clearly demonstrated for the first time in the U.S. under our study protocol, thanks to the splendid work done by Dr. Darren L. Bergey, at the Bergey Spine Institute in Colton, CA," Mr. Cuevas continued.

 

"The ability to offer our patients less invasive procedures to treat their back pain with clinical outcomes equal to or better than we see in open fusion surgery is what we are all about at the Bergey Spine Institute," said Dr. Bergey, an orthopedic spine surgeon. "This objective provided the impetus to my participation as an investigator in Interventional Spine's study. The study's first patient was a 62 year old male. We performed a percutaneous two-level (L-4 to S-1) PDS System procedure in our state of the art out-patient surgery facility, and sent him home today sitting in the front seat of his own car. Our expectation is for this patient to be able to return to a normal, pain free life in just a matter of days," Dr. Bergey concluded.

 

"We are delighted to begin this study and expect patient enrollment to accelerate at a number of clinical sites over the next few weeks. We thank Dr. Bergey and his team and wish his patient the very best outcome possible. This milestone is another step forward in uniquely positioning Interventional Spine for growth in the United States. The PDS System is commercially available outside the U.S. under the PercuDyn System name, and our earliest patients are now beyond a three-year follow-up period with outstanding results," commented Mr. Cuevas, who added, "Detailed information on the PercuDyn System will be presented at the upcoming SAS '09 Meeting in London at the end of this month."

 

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QRxPharma Successfully Completes Comparative Study for Dual-Opioid Pain Therapy

Primary Endpoints Met; Data Demonstrate MoxDuo(TM) IR Provides Better Tolerability Than Morphine and Oxycodone Alone

 

QRxPharma Limited announced today the successful completion of a Phase 3 program pilot study comparing the efficacy and safety profile of MoxDuo IR against component doses of morphine and oxycodone. Results demonstrated that MoxDuo IR reduces pain significantly more than its component doses; further, when compared to equianalgesic doses of morphine and oxycodone, MoxDuo IR produced fewer and less intense side effects. These results confirm 12mg/8mg morphine plus oxycodone combination as the preferred dose for optimal efficacy and tolerability as well as provide sample size guidance for the upcoming Phase 3 Combination Rule study required for NDA submission in 2010.

 

In this randomized, double blind study of 197 patients at 6 US clinical research sites, MoxDuo IR was compared to morphine and oxycodone in managing acute pain during the first 24 hours following a scheduled surgical procedure (bunionectomy). When postoperative pain reached a measure of at least "4" (moderate pain, with 10 being the most severe) on the Numerical Pain Rating Scale, patients received either MoxDuo IR, morphine or oxycodone every 6 hours for 48 hours. The study's primary clinical endpoint was changes in the pain intensity scores from baseline for MoxDuo IR versus component doses of morphine and oxycodone alone. Secondary endpoints included: (1) pain relief and global assessment of effect; and (2) safety as measured by the incidence and intensity of opioid-related adverse events.

 

In terms of reduced pain intensity scores and other related measures, the analgesic effects of 12mg/8mg MoxDuo IR were 80-100% greater than the components, morphine or oxycodone. The 6mg/4mg MoxDuo IR dose also showed similar improvements when compared to its individual components.

 

Significantly, the frequency of moderate to severe adverse events (including nausea, vomiting, constipation, dizziness, etc.) was 25% to 75% lower among patients on MoxDuo IR compared to those receiving equi-analgesic doses of morphine or oxycodone alone. Furthermore, patients receiving morphine or oxycodone alone were two to four times more likely to prematurely discontinue dosing than those on MoxDuo IR.

 

Additional studies evaluating MoxDuo IR versus Percocet in patients with joint replacement surgery are underway, with results expected in Q3 of 2009.

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HBL Portfolio Company Tolarex to Commence Phase I/IIa Trial of a Treatment for GVHD

Tolarex, a Hadasit Bio Holdings Ltd (HBL) portfolio company, announced today that it has received approval by the Ministry of Health of Israel to begin a phase I/IIa clinical trial of its treatment for graft-versus-host disease (GVHD).

 

The first in man trial, anticipated to begin shortly, will evaluate the safety and preliminary possible efficacy of Tolarex's therapy. Twelve patients will be enrolled at two medical centers in Israel, Hadassah University Hospital in Ein Kerem included.

 

Assuming positive results of the trial announced today, Tolarex has plans to explore other potential applications of its treatment within the billion dollar autoimmune and inflammatory disease market, including solid organ transplant and stent implantations.

 

Alon Moran, CEO of Tolarex said, "The green light from Israel's Ministry of Health signifies the maturity of the technology and its readiness to transfer to the clinical stage. We are also hopeful that today's news will advance negotiations towards joint development or commercialization of the technology with potential partners."

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Cytokinetics Announces Non-Clinical Data Relating to CK-2017357 Presented at the 2009 Experimental Biology Conference

Cytokinetics, Incorporated announced today that a poster containing data relating to CK-2017357, a fast skeletal muscle troponin activator, was presented at the 2009 Experimental Biology Conference held from April 18-22, 2009 in New Orleans, Louisiana. Cytokinetics plans to initiate a Phase I clinical trial of CK-2017357 in healthy volunteers later this year.

 

Poster Presentation at 2009 Experimental Biology Conference:

The poster titled, "The Fast Skeletal Troponin Activator, CK-2017357, Increases Skeletal Muscle Force in vitro and in situ," was presented on Sunday, April 19, 2009 by Alan Russell, Ph.D. of Cytokinetics. The objective of the study was to evaluate whether CK-2017357 changes force development in native skeletal muscle preparations in vitro, using skinned and living skeletal muscle fibers, and in situ, where nerve and blood supply are left intact. The authors demonstrated that CK-2017357 increased sub-maximal force development of fast skeletal muscle in vitro. Similar findings were observed in human skinned fast skeletal muscle fibers. In addition, compound specificity for fast skeletal muscle fibers was shown as skinned slow skeletal muscle fibers were approximately ten-fold less responsive to CK-2017357 than skinned fast skeletal muscle fibers. CK-2017357 did not appear to activate cardiac muscle fibers. CK-2017357 increased the force development in living muscle fibers at sub-maximal stimulation frequencies. Finally, in situ, CK-2017357 increased sub-maximal force development in a predominantly fast skeletal fiber muscle (extensor digitorum longus).

 

The authors concluded that these data support a proposed mechanism of action of CK-2017357 through calcium sensitization of the fast skeletal muscle troponin complex. In skinned muscle fibers, CK-2017357 increased the sensitivity of skeletal muscle to exogenously added calcium and in living muscle fibers to the frequency of electrical stimulation which results in calcium release within the muscle. In each case, the result is an increase in muscle force development at sub-maximal muscle activation, where muscle normally operates.

 

 

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Poniard Announces Publication of Results of Picoplatin Phase 2 Study in Journal of Clinical Oncology

Findings Demonstrate Survival Benefit with Picoplatin as Second-Line Therapy for Small Cell Lung Cancer -

 

Poniard Pharmaceuticals, Inc., a biopharmaceutical company focused on oncology, today announced that results of its Phase 2 clinical trial of picoplatin in patients with recurrent small cell lung cancer (SCLC) were published in the April 20, 2009, print issue of the Journal of Clinical Oncology(1). Picoplatin demonstrated a survival benefit in this open-label, multi-center Phase 2 trial of SCLC patients who failed prior platinum-containing first-line chemotherapy or who progressed within six months of first-line therapy. The median overall survival was 27 weeks and the median one-year survival rate was 17.6 percent in this patient population of mostly platinum-refractory and -resistant patients.

 

Poniard is currently evaluating the efficacy and safety of picoplatin in the pivotal Phase 3 SPEAR (Study of Picoplatin Efficacy After Relapse) SCLC trial, which is being conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA). The Company reached its enrollment target in this international, multi-center, randomized, controlled trial in March 2009.

 

Phase 2 Study Design and Results

The open-label, multi-center Phase 2 trial was designed to confirm the clinical activity and safety of picoplatin as second-line therapy in patients with platinum-refractory disease or platinum-resistant or platinum-sensitive disease that had progressed within six months after first-line treatment with a platinum-based chemotherapy, such as cisplatin or carboplatin. Efficacy endpoints included response rates, progression-free survival, overall survival, improvement in disease-related symptoms and disease control (defined as complete response, partial response and stable disease). The trial was conducted at clinical sites in North America and Eastern Europe.

 

A total of 77 patients received picoplatin. Median overall survival was 27 weeks following picoplatin administered once every three weeks. Median progression-free survival was 9 weeks. The six-month and one-year survival rates were 51 percent and 17 percent, respectively. The disease control rate was 47 percent in the 77 evaluable patients. The most common side effects observed were hematologic and included thrombocytopenia, neutropenia and anemia. No grade 3 or 4 neurotoxicity or nephrotoxicity and no treatment-related deaths occurred in the study.

 

"The publication of these clinical findings in JCO represents an important milestone for Poniard. The positive survival results of the Phase 2 picoplatin trial in this difficult-to-treat disease formed the basis of our decision to initiate the Phase 3 SPEAR trial for which we recently completed patient enrollment ahead of internal projections," said Robert De Jager, M.D., chief medical officer of Poniard. "We are on track to complete the clinical data analysis of the SPEAR trial and initiate the filing of a rolling New Drug Application with the FDA for picoplatin in SCLC this year. If approved, picoplatin could represent an important new treatment for SCLC. In addition, it potentially enables other trials of picoplatin in patients with other solid tumors who relapse or are refractory to first-line platinums, such as in non-small cell lung cancer and ovarian cancer."

 

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ArQule Presents Three Studies at AACR 100th Annual Meeting 2009

ArQule, Inc. today announced that the Company is presenting three studies at the AACR (American Association for Cancer Research) 100th Annual Meeting 2009, April 18-22, 2009 in Denver, Colorado.

 

These pre-clinical studies include two ArQule compounds in clinical development: ARQ 197, a selective inhibitor of the c-Met receptor tyrosine kinase, and ARQ 621, a novel inhibitor of the Eg5 kinesin motor protein.

 

Summaries of ArQule presentations at AACR

 

ARQ 197 / c-Met Inhibition

 

1. Combination studies of tyrosine kinase inhibitors (TKIs): Assessment of potential cytotoxic synergy of ARQ 197 with sorafenib or sunitinib (Abstract Number 820, Poster Section 35, Poster Board Number 6, Hall B-F, April 19, 2009, 8:00 AM – 12:00 PM)

 

ArQule researchers examined the potential synergy in vitro of ARQ 197 with two marketed tyrosine kinase inhibitors (TKIs), sorafenib and sunitinib. The combination of ARQ 197 and sorafenib showed synergistic cytotoxicity in non-small cell lung cancer, breast cancer, melanoma, small cell lung cancer and cervical cancer cell lines. Additive cytotoxicity with this combination was shown in breast cancer, colon cancer, renal cell carcinoma, squamous cell carcinoma, non-small cell lung cancer and hepatocellular carcinoma cell lines. In vivo confirmation of some of these findings in a human tumor xenograft model was also presented. The combination of ARQ 197 and sunitinib showed synergistic cytotoxicity in gastric carcinoma cell lines and additive cytotoxicity in a number of cancer cell lines. ARQ 197 and sorafenib showed synergy and additive effects in a larger number of cell lines than did ARQ 197 and sunitinib. These data suggest the potential clinical utility of combining ARQ 197 with other TKIs in cancer therapies.

 

2. Inhibition of the HGF/c-Met pathway by ARQ 197: Characterization of pharmacodynamic markers in vitro and in vivo (Abstract Number 1748, Poster Section 35, Poster Board Number 10, Hall B-F, April 19, 2009, 1:00 PM – 5:00 PM)

 

C-Met inhibition by ARQ 197 in human tumor cells was demonstrated through the analysis of two c-Met phosphorylation sites and downstream signals. Immunofluorescent staining of human gastric cancer (MKN45), colon cancer (HT29), and breast cancer (MDA-MB-231) cells in vitro showed clear reduction of c-Met phosphorylation after exposure to ARQ 197 in a concentration-dependent manner. Maximum inhibition was observed after 24 hours of ARQ 197 treatment and was sustained for at least eight hours following the removal of the compound. These findings were further supported by pharmacodynamic analysis of human tumor xenograft tissue data. The pharmacodynamic effect of ARQ 197 on c-Met and downstream markers, which has been confirmed in human tumor biopsies, provides a rationale for biomarker strategies in the clinical development of ARQ 197.

 

ARQ 621 / Eg5 Inhibition

 

3. Therapeutic potential of ARQ 621, a novel Eg5 kinesin inhibitor with low bone marrow toxicity (Abstract Number 4604, Poster Section 34, Poster Board Number 7, Hall B-F, April 21, 2009, 1:00 PM – 5:00 PM)

 

Interest in Eg5 inhibition as an anti-cancer therapy has increased following recent research showing that over-expression of Eg5 promotes both genomic instability and tumorigenicity. However, previous inhibitors of Eg5 have been associated with bone marrow suppression, raising the concern of potential mechanism-related toxicity. In this study, ARQ 621, a novel clinical stage drug candidate, was shown to inhibit human Eg5 potently and selectively in pancreatic cancer, breast cancer, prostate cancer and ovarian carcinoma cell lines. Furthermore, no hematological changes were observed at efficacious doses in xenograft studies. Repeated intravenous infusions of ARQ 621 over a 28-day period in rats and dogs confirmed that there was no observed compound-related neutropenia, and the myeloid/ erythroid ratio was unchanged in bone marrow of treated dogs. These data suggest that treatment with ARQ 621 may yield a wider therapeutic window than observed in first generation Eg5 inhibitors. Phase 1 clinical testing of ARQ 621 is ongoing.

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Medarex Announces Clinical Data for MDX-1401 in Hodgkin's Lymphoma at Annual Meeting of the American Association for Cancer Research

Medarex, Inc. today announced preliminary data from an ongoing Phase 1 clinical trial of MDX-1401 in patients with relapsed or refractory Hodgkin's lymphoma (HL) that demonstrated both clinical and immunological activity signals. MDX-1401 is a fully human, non-fucosylated antibody that targets CD30, a marker for activated lymphocytes that is present on malignant cells of HL as well as other CD30-expressing cancers. Results from the study were presented in a poster session (Abstract #1227) at the Annual Meeting of the American Association for Cancer Research (AACR), held April 18-22, 2009 in Colorado.

 

An ongoing multi-dose, dose-escalation Phase 1 trial of MDX-1401 in patients with relapsed or refractory HL is being conducted to establish and evaluate the safety profile and initial efficacy of MDX-1401. Preliminary data from the Phase 1 trial demonstrate that multiple doses (ranging from 0.01 to 1.0 mg/kg) of MDX-1401 in patients with HL were generally safe and well-tolerated. Two of the 8 patients with stable disease had a reduction of 40 percent or more in tumor burden after two treatment cycles of MDX-1401. In addition, flow cytometry indicated decreased circulating CD30 positive cells in 83 percent of patients (10/12) after one cycle of four weekly intravenous infusions.

 

"We find these preliminary safety and efficacy data for our second generation anti-CD30 antibody encouraging," said Geoffrey M. Nichol, MBChB, Senior Vice President of Product Development at Medarex. "We are currently enrolling additional patients at higher dose levels and look forward to examining further results from the ongoing Phase 1 trial."

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Pharmasset Voluntarily Halts Clinical Studies with Clevudine in Hepatitis B Infected Patients

Pharmasset, Inc. announced today that after a discussion with its independent Data Safety Monitoring Board (DSMB) and the FDA, the company has decided to voluntarily terminate its Phase III QUASH studies of clevudine for the treatment of chronic hepatitis B (HBV) infection.

 

Pharmasset recently became aware of a number of spontaneous Serious Adverse Event reports and Events of Special Interest in patients receiving clevudine as prescribed therapy for hepatitis B in South Korea. Though only a small number of cases of mild to moderate myopathy, or muscle weakness associated with creatine kinase elevations, were reported in the QUASH studies, many of the patients in South Korea have had longer exposures to clevudine than patients in the QUASH studies and have reported more serious myopathy than have patients in the Pharmasset clinical trials. Given the number and severity of cases observed in South Korea, Pharmasset concluded it was in the best interest of patients to terminate the studies at this time.

 

"The safety of patients in the QUASH studies is our top priority and, therefore, we have decided to stop treatment with clevudine," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "Although the number of cases of myopathy in the QUASH trials was low and the severity was mild, more severe reports from other trials and post marketing surveillance led us to believe the risk benefit ratio for clevudine was insufficient to continue development. We would like to take this opportunity to thank patients and our investigators for their participation in the QUASH studies."

 

As part of the study shut down, Pharmasset plans to continue to collect safety data and to monitor patients after discontinuation of clevudine in the QUASH studies, but does not plan to submit study results to regulators as pivotal studies. Clevudine was licensed from Bukwang Pharmaceuticals of South Korea, where the drug is marketed under the trade name Levovir.

 

"While we are obviously disappointed with the outcome, we believe the decision to stop dosing is an appropriate one," stated Schaefer Price, President and Chief Executive Officer. "Our full energy and resources in research and development will now be focused on our promising HCV pipeline. Our partner Roche will shortly initiate dosing in a phase 2b trial with R7128, and will report interim data from the INFORM-1 trial at the upcoming EASL meeting. Pharmasset's unpartnered second generation HCV nucleoside, PSI-7851, is progressing well in a phase I trial and we expect to report the first antiviral data in the second half of 2009. In addition, we are collecting preclinical data from our research efforts to select a purine nucleos(t)ide for clinical development."

 

The QUASH studies are international, multi-center, randomized, double-blind clinical trials of 30mg once daily clevudine compared with 10mg once daily adefovir for 96 weeks in patients with chronic hepatitis due to infection with e-antigen positive hepatitis B virus (QUASH 305) or e-antigen positive (QUASH 306) who have never been treated with drugs of the nucleoside class. The primary objective of the studies are to assess the effect of clevudine on reducing levels of virus in the blood and normalization of liver function at 48 weeks after initiating therapy.

 

Members of Pharmasset's management team will host a conference call today, Monday, April 20, 2009, at 8:00 a.m. ET to discuss the decision to terminate the studies. Investors may listen to the webcast of the conference call live on the "Events & Presentations" section of Pharmasset's website, . Alternatively, investors may listen to a replay of the call by dialing (888) 806-6202 from locations in the U.S. and (913) 312-1502 from outside the U.S. The call-in replay and webcast will be available for at least 72 hours following the call.

 

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Phytopharm: Commencement of Clinical Study of Cogane in Patients with Parkinson's disease

Phytopharm plc today announces the commencement of a safety, tolerability and pharmacokinetic (PK) study of its orally active neurotrophic factor inducer PYM50028 (Cogane), which will involve both healthy volunteers and patients with Parkinson's disease (PD). This follows approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) and Research Ethics Committee to commence recruitment for the UK study.

 

In pre-clinical models, Cogane reverses the changes in the area of the brain involved in Parkinson's disease by inducing the body's own production of proteins known as neurotrophic factors. In particular, one of these factors known as "GDNF" has been shown to be particularly effective in re-growing damaged nerves. Since GDNF is a protein it cannot be given orally (in pill or liquid form) because it is degraded in the stomach and intestine, and also does not readily cross the blood-brain barrier. GDNF can work only when injected into or when produced inside the brain. Direct injection of GDNF into the area of the brain involved in Parkinson's disease has shown substantial beneficial effects in small-scale clinical studies but requires highly complex and difficult surgical procedures. Cogane, which can be taken orally, readily crosses the blood-brain barrier and stimulates the release of GDNF in the brain and therefore has the potential to overcome many of the difficulties associated with GDNF administration. The current study, to be conducted on a part residential, part out-patient basis, will employ a randomised, double-blind, multiple dose-ascending, placebo-controlled design to evaluate the safety, tolerability and PK profile of a new oral solution formulation of Cogane when taken for up to 28 days at various dose levels. In total, 18 healthy male and female volunteers and up to 18 male and female patients with PD aged between 40-80 years, are planned to be enrolled with doses being escalated sequentially following a safety review at each dose level.

 

The primary objective of this study is to confirm the safety and tolerability of Cogane in healthy subjects and PD patients when administered at these dose levels for up to 28 days, the secondary objective being to determine the plasma PK profile of Cogane in these subjects.

 

Significantly, the range of doses to be administered in this study has been selected to target plasma levels of Cogane equating to therapeutically relevant concentrations in preclinical disease models. The PK data from this study should facilitate dose selection for a Phase IIb proof-of-concept study in PD patients.

 

Dosing of the first group of enrolled subjects has commenced with enrolment expected to be completed in Q3 of this year and the results reported in Q4.

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Impax Pharmaceuticals Reports Positive Achievements on its Two Leading Brand Product Candidates IPX066 and IPX056

Impax Pharmaceuticals, the brand products division of Impax Laboratories, Inc. today announced it has commenced a Phase III trial of IPX066 in Parkinson's Disease (PD) patients based on encouraging interim data collected from the Phase II study in PD patients. It also clarified the U.S. Food and Drug Administration (FDA) requirement for pediatric studies of its investigational medication IPX056.

IPX066 for Parkinson's Disease
Impax Pharmaceuticals has started enrolling patients in a Phase III trial of its late-stage drug candidate IPX066 in PD patients. IPX066 is an investigational extended release carbidopa levodopa product intended to produce a fast and sustained concentration of levodopa, potentially improving PD clinical symptom management.

Impax has completed multiple Phase I pharmacokinetic studies in healthy volunteers and will soon complete a open label and active-controlled Phase II study in PD patients. The interim results of this Phase II study have demonstrated consistent signals of superior clinical benefit in both extended pharmacokinetic profile and control of PD motor symptoms compared to conventional carbidopa levodopa.

Based on both confirmatory Phase I and compelling interim Phase II data, the company has commenced enrollment in the first Phase III study, also known as APEX-PD, in PD patients with mild symptoms of PD. The company is conducting this trial under a recent agreement with the FDA through a Special Protocol Assessment (SPA) for the Phase III clinical trial of IPX066 in PD patients.

Impax is planning to commence a second Phase III trial of IPX066 in patients with advanced PD patients later in 2009 or early 2010.

Michael Nestor, divisional president of Impax Pharmaceuticals said: "We are delighted with the efforts of our impressive team headed by Dr. Suneel Gupta which has rapidly advanced IPX066 from an Investigational New Drug (IND) filing (July 2008) to Phase III commencement under SPA in nine months. We are eager to continue the successful development of this product and bring the potential benefits of IPX066 to physicians who treat Parkinson's and their patients as quickly as possible. We continue to work towards our goal of filing a New Drug Application (NDA) in the fourth quarter of 2011."

Impax plans to submit the Phase II data for presentation at a future clinical meeting.

About the APEX-PD Phase III Study
-- The APEX-PD study is a Phase III randomized, double blind, placebo-controlled study to evaluate the safety and efficacy of IPX066 in subjects with PD. The study will evaluate three doses of IPX066 versus placebo in subjects with mild symptoms of PD.
-- The trial is expected to enroll approximately 350 subjects who will be randomized into one of four treatment groups.
-- The trial will be conducted at multiple sites in North America and Europe.
-- The agreed upon primary endpoint is change from baseline in the sum of Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III. Additional endpoints include clinical and patient reported outcome measures.

 

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Momenta Pharmaceuticals Presents Preclinical Data for Novel Oncology Compound M402 at AACR Meeting

Momenta Pharmaceuticals, Inc., a biotechnology company specializing in the characterization and engineering of complex mixture drugs, today announced results from a preclinical study of its novel oncology drug candidate, M402. The data showed that M402 in combination with chemotherapeutic agents inhibited spontaneous tumor metastasis in a murine metastatic breast carcinoma model. The results were presented in a poster session titled "M-ONC 402 - A Non-Anticoagulant Low Molecular Weight Heparin Inhibits Tumor Metastasis" (abstract #281) on Sunday, April 19, 2009 at the 100th Annual Meeting of the American Association for Cancer Research (AACR), in Denver, Colorado.

 

M402 is an HSGAG mimetic engineered from low molecular weight heparin (LMWH) to have potent anti-metastatic properties and low anticoagulant activity. Anti-tumor efficacy was first evaluated in an experimental murine melanoma metastasis model. The data demonstrated that a single dose of M402 administered prior to tumor inoculation significantly reduced tumor colonization in the lung in a dose-dependent manner. Based on these findings, the anti-tumor efficacy of M402 was then assessed for the ability to inhibit spontaneous metastasis in an orthotopic murine metastatic breast carcinoma model. In this model, M402 in combination with cisplatin was shown to significantly inhibit tumor cell metastasis to the lung compared to animals treated with cisplatin alone. Subsequent immunohistological analysis showed a decrease in microvessel density in both primary tumors and lung metastases in the M402 treated group, suggesting that anti-angiogenesis may contribute to the anti-tumor effect of M402.

 

Additional preclinical studies of M402 will be presented at AACR in a poster "M-ONC 402, a Novel Non-Anticoagulant Heparin Inhibits P-selectin Function and Inhibits Metastatic Seeding of Tumor Cells in Mice" (abstract #5005) on Wednesday, April 22, 2009 from 8:00 AM - 12:00 PM.

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NanoBio Initiates FDA Approved Clinical Trial for Adjuvanted Intranasal Influenza Vaccine

Phase 1 Study to Demonstrate Safety and Proof of Concept for Highly Effective, Non-Inflammatory, Nanoemulsion Adjuvant Platform Technology

 

NanoBio Corp. announced today that the U.S. Food and Drug Administration (FDA) has approved the company's Investigational New Drug (IND) application for the Phase 1 clinical study of NB-1008, a seasonal influenza vaccine administered via a nasal dropper. NB-1008 uses a novel nanoemulsion-based adjuvant to achieve a robust immune response using only a small fraction of the antigen required by currently available injectable vaccines. In numerous animal studies, NB-1008 has demonstrated robust mucosal, systemic and cellular immunity without inflammation or safety concerns.

 

The underlying technology for NB-1008 is NanoBio's NanoStatTM platform, which employs a nanoemulsion that is created through a proprietary manufacturing process. The nanoemulsion is uniquely capable of permeating the nasal mucosa, where it can load vaccine antigen into immune-presenting cells. These cells then carry the antigen to areas of the body that initiate an immune response, including the lymph nodes, thymus and spleen. NanoBio is in various stages of preclinical development for numerous other nanoemulsion-adjuvanted vaccines, including hepatitis B, pandemic influenza, RSV, HIV, pneumococcal, cancer, anthrax and smallpox.

 

The Phase 1 trial is a randomized, controlled study in the United States involving 120 healthy human volunteers. The primary endpoints are safety and immunogenicity as determined by neutralizing serum antibodies.

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Amira Initiates Phase I Clinical Trial of Novel DP2 Antagonist

Trial Will Evaluate Safety, Proof of Mechanism of a Potential Oral Antagonist for the Treatment of Asthma and COPD

 

Amira Pharmaceuticals, Inc., announced today the initiation of a Phase I clinical study of AM211, its internally discovered oral drug candidate for the treatment and control of inflammatory and allergic diseases linked to the arachidonic acid pathway.

 

AM211 is an oral, selective antagonist of the receptor DP2, which recent studies have shown to be a potential target for the treatment of asthma, chronic obstructive pulmonary disease (COPD) and allergic rhinitis. The Phase I study is designed to obtain safety and proof of mechanism data for AM211.

 

DP2 is also known as CRTH2 or chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes. DP2 is a high affinity receptor for prostaglandin D2 and, in humans, is implicated in Th2-dependent allergic inflammation.

 

"The start of the AM211 clinical studies marks another impressive milestone in our company's short existence. Our small but effective team has been able to bring three distinct molecules into the clinic in less than four years," said Bob Baltera, Amira's Chief Executive Officer. "We look forward to continuing this pace as we advance our next program for idiopathic pulmonary fibrosis toward the clinic.

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Peregrine Pharmaceuticals Reports Positive Preliminary Data From Phase II Bavituximab Lung Cancer Trial

- Updated Data from Initial Cohort Shows 11 of 17 Evaluable Patients Receiving Bavituximab in Combination with Carboplatin + Paclitaxel Achieved an Objective Tumor Response

- Patient Dosing Initiated in Expansion Stage of Trial with Target of Enrolling 49 Patients Overall -

 

Peregrine Pharmaceuticals, Inc., today announced that updated preliminary data from the initial cohort of 21 patients in its Phase II trial evaluating bavituximab in combination with carboplatin and paclitaxel showed that 11 of 17 evaluable patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) achieved an objective tumor response according to RECIST criteria, after completing the maximum six treatment cycles. The company also reported that patient dosing is underway in the expansion stage of the trial, which will enroll an additional 28 patients for a total of 49 patients overall.

 

The primary objective of the multi-center, open-label Phase II study is to assess the overall response rate to bavituximab with carboplatin and paclitaxel. In the trial's Simon two-stage design, 21 patients with previously untreated locally advanced or metastatic NSCLC were initially enrolled and 17 of these patients were deemed evaluable. In this initial cohort, 11 of the 17 evaluable patients achieved an objective tumor response by the time that treatment with the combination of bavituximab, carboplatin and paclitaxel was completed. Eight of the 11 objective tumor responses were confirmed by at least one repeat scan no less than four weeks after the criteria for response were first met.

 

Secondary objectives of the study include measuring time to tumor progression, duration of response, overall patient survival and safety parameters. Patients in the study are evaluated regularly for tumor response according to RECIST criteria. Patients may continue to receive bavituximab as monotherapy after completion of chemotherapy as long as the cancer does not progress and side effects are acceptable. The trial is being conducted in India according to International Conference on Harmonization (ICH) and Good Clinical Practices (GCP) guidelines.

 

 

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Medical Center on cutting edge of drug treatments

When Becky Meyer was diagnosed with breast cancer at age 61, her doctor and an oncology research nurse at The Medical Center of Central Georgia offered her a new treatment: a drug called Avastin.

 

The drug is known to cut off blood flow to cancerous tumors but hasn't yet been approved by the Food and Drug Administration for use on her type of breast cancer.

 

 

Meyer, a retired nurse, went home and talked with her husband about it. She researched Avastin online. She decided she trusted her doctor.

 

Meyer said yes.

 

Nine months later, she has had surgery and chemotherapy and is still taking the Avastin. The regimen seems to have whipped the cancer, she said.

 

"I feel like I've done really well," Meyer said. "I hope my having taken this drug will help them with the treatment of this disease in the future."

 

The Avastin trial is one of about 30 currently running at the Medical Center, which also continues to follow the subjects of about 20 other past studies, said hospital clinical research manager David King.

 

The hospital's status as a research institution and its partnership with Mercer University means that Macon has long been an incubator for new treatments, some of which are now considered the gold standard, research managers say. Mercer also participates in outpatient trials independently, as do some private doctors in the city.

 

But although trials put the Medical Center and its patients on the cutting edge of new research, they also pose risks. The treatments haven't been broadly approved by the FDA, and sometimes the side effects and interactions aren't yet understood.

 

By law, patients must be informed of those risks before deciding whether to participate. It can be a difficult decision that sometimes must be made immediately, as in the case of trauma or heart attack patients.

 

Raj Patel, a doctor of internal medicine with the hospital and Mercer, noted that participating in research increases the prestige of the hospital. But the real point is providing better treatment for the types of disease most often seen at the Medical Center, he said.

 

For example, as a Level 1 trauma center in a region with rampant heart disease and diabetes, the Medical Center often looks for trials focused on these specialties — even though they can be some of the most complex to conduct, Patel said. Consent and treatment must happen very rapidly.

 

A few years ago, the hospital participated in the trial of a blood substitute for use with trauma victims. The trial became controversial because generally its subjects couldn't agree to participate until after they had already received the product.

 

PAST AND CURRENT STUDIES

 

Contrary to the stereotype, most drug trials aren't last-ditch efforts to cure terminal illness, King said.

 

Nevertheless, many Medical Center trials have dealt with cancer or heart disease. And Mercer has been a pioneer in trials for HIV and AIDS treatment, having been a trial site for many of the most common therapies used today, said Sophia James, research administrator for the Mercer Medical School in the department of internal medicine.

 

"Mercer has never done a study of a drug that wasn't later approved," she said.

 

For cancer treatment, the hospital conducts inpatient studies and works with Central Georgia Cancer Care on trials that continue through outpatient treatment.

 

"We're starting to look more at targeted therapies that do things like shrink tumors or inhibit the formation of blood vessels to tumors," said Julie Gioscio, an oncology research nurse at the Medical Center.

 

For example, the hospital participated in the trial of Herceptin, a drug that slows or stops the growth of the cells that make tumors grow faster and come back after treatment. Herceptin is now a standard breast cancer treatment, she said.

 

The Medical Center is known for its heart center, which has often tried out new devices in its catheterization lab, said Carrie Knott, cardiovascular research manager.

 

In 2002, the hospital helped test the first drug-coated stents. Stents are metal mesh tubes used to hold an artery open to maintain blood flow. Drug-coated stents are now commonly used to inhibit the growth of scar tissue, reducing blockages and the need for additional surgery, Knott said.

 

A current trial is testing which medicines work best for patients who have both high blood pressure and heart failure, Patel said.

 

"We have a large population with heart failure in Macon," he said. "We also have a big problem with high blood pressure and diabetes."

 

Patients get involved in these trials through different avenues. Most are approached, as Meyer was, by their doctor and a hospital research coordinator.

 

Some refuse. Knott said patients may say "they don't want to be a guinea pig."

 

Others volunteer. Cancer patients may seek out a trial they have read about online and drive to Macon from an hour away to participate, Gioscio said.

 

Newspaper advertisements were used to attract Macon-area subjects for hypertension and arthritis treatment trials, James said.

 

James noted that trial participants actually see their doctors more often than they would otherwise and receive more follow-up tests, all at no extra charge.

 

"So patients often feel they get more attentive care in a trial," James said.

 

PRIOR CONSENT IN EMERGENCIES

 

Some types of trials, especially those that deal with subjects who are in life-or-death emergencies, are conducted without patients directly consenting first.

 

Several years ago, the Medical Center was the only test location in Georgia for PolyHeme, a blood substitute being developed for use on the battlefield and in other situations when blood supplies are limited. Because the trial focused on trauma victims, most patients were unconscious when the product was first given. The study provoked outrage among some national consumer groups.

 

Instead of traditional consent beforehand, the FDA approved using community education campaigns to inform people that they could obtain armbands to wear all the time for more than a year, which would exclude them from the study.

 

The Medical Center held eight town hall meetings at different times and locations across Bibb and Jones counties — advertised in the newspaper — and set up a toll-free hotline for comments or opt-out requests, said study coordinator Deborah Kitchens. Attendance at most of the meetings was sparse, she said.

 

Kitchens estimated that she gave out 400 armbands, including 200 requested by a single church. About 80 percent of the armbands were requested by Jehovah's Witnesses, who frequently refuse blood transfusions for religious reasons, she said.

 

In the study, PolyHeme was given instead of a salt solution to patients in an ambulance. For the first 12 hours of treatment — or six units of PolyHeme, whichever came first — they continued to receive the product instead of blood transfusions, Kitchens said.

 

But as soon as the patient arrived at the hospital, the patient or family member had to be informed about the PolyHeme and provide consent for it to continue, she said.

 

"If we didn't have consent, we had to document every 15 to 30 minutes why we didn't," she said. Patients could pull out of the study at any time.

 

After the television program "20/20" ran a story about the lack of advance consent in the PolyHeme trial, some Macon residents called, cursing at Kitchens.

 

"You don't tell Americans they don't have a say-so in their care," she said. "They lose it."

 

But she compared the trial to the many times when an emergency responder decides which hospital to take an unconscious patient. Despite criticism of the trial, Kitchens said she thinks the hospital would conduct a similar experiment in the future if a promising product became available. None of the local subjects had adverse reactions to PolyHeme, she said.

 

"We were interested because it was a trauma trial, and I just think we need something like this," Kitchens said. "You hear things all the time about blood banks running dry."

 

In addition, PolyHeme has a longer shelf life than blood and can be given to anyone regardless of blood type.

 

Since the trial, PolyHeme still has not been approved by the FDA. King said the hospital frequently never learns the results of the full studies in which it participates.

 

The Medical Center currently is involved in another trial of a product delivered in ambulances, although patients are only enrolled if they are capable of consenting.

 

The study is testing out a solution of glucose, insulin and potassium for preventing a threatening heart attack or to reduce the risk of serious complications and death from a heart attack while it's occurring, said Kelly Joiner, assistant director for The Medical Center EMS.

 

Macon is one of eight sites across the country involved in the study, which is designed to include 880 patients in all, she said.

 

"If found effective, it will change our standard of care across the nation," she said. "It will be a cost-available drug for ambulances to carry."

 

Previous studies have shown the solution to be most effective when it's given as early as possible, so trying it before the patient even reaches the hospital makes sense, she said.

 

"There's not a lot of research in EMS, and it's needed," Joiner said. "There's a greater understanding in the medical community that EMS is an under-utilized resource. We're the first medical professional that people see, and for people in rural areas, we may be with them for almost an hour before they arrive at the hospital."

 

To contact writer S. Heather Duncan, call 744-4225.

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IXICO Launches Trial Wire, a Free, Web-based Tool for De-identifying, Organizing, and Moving Medical Image Data

Today, at the ISMRM conference in Hawaii, IXICO has released a free medical image management tool, Trial Wire. Trial Wire is a web-based tool for de-identifying, organizing, and electronically transferring medical images in the global standard DICOM format. Developed by IXICO's team of in-house medical imaging experts to maximize speed and efficiency of image data management, Trial Wire's unique technology is already being used for handling image data collected at many dozens of sites around the world. IXICO is now making Trial Wire available to anyone interested in medical image data management, whether they are involved in imaging-based clinical trials, research, or simply need a tool for efficient image data management.

 

Today, at the ISMRM conference in Hawaii, IXICO has released a free medical image management tool, Trial Wire. Trial Wire is a web-based tool for de-identifying, organizing, and electronically transferring medical images in the global standard DICOM format. Developed by IXICO's team of in-house medical imaging experts to maximize speed and efficiency of image data management, Trial Wire's unique technology is already being used for handling image data collected at many dozens of sites around the world. IXICO is now making Trial Wire available to anyone interested in medical image data management, whether they are involved in imaging-based clinical trials, research, or simply need a tool for efficient image data management.

 

Trial Wire 2.0 beta allows users to easily de-identify image data to help maintain compliance with global patient privacy regulations, including HIPPA and the EU Directive on the Protection of Personal Data. The tool also allows users to organize image data into DICOM hierarchical structures and then transfer the data securely over the internet.

 

However, it is currently a huge amount of effort to handle this data in a way that preserves patient privacy and organizes the data in a way that is easy to use. We wanted to offer a product that addresses the most basic issues of image data management, and make it freely available

As a bonus feature, Trial Wire provides a complete audit trail (a record of everything done to the data and by whom it was done), which can be saved electronically or printed and filed. Whether users need to sort through and organize archived image data or securely transfer de-identified data to a CRO or clinical trial sponsor (or simply from a hospital to an adjacent research lab), Trial Wire can be accessed from any web-enabled computer.

 

"Medical imaging is very widely used for clinical trials and research", said Derek Hill, CEO of IXICO. "However, it is currently a huge amount of effort to handle this data in a way that preserves patient privacy and organizes the data in a way that is easy to use. We wanted to offer a product that addresses the most basic issues of image data management, and make it freely available", said Derek Hill, CEO of IXICO. "By providing de-identification, organization, and transfer in an easy-to-use web-based tool, we believe we can help the entire imaging research community improve its efficiency while ensuring that patient privacy is protected. We believe that the best way to make a positive impact on these issues is to foster the widespread adoption of a single, easy-to-use, web-based tool. No one should have to pay for image data transfer any more than they should have to pay to send an email or other file over the internet. In addition to the secure transfer function, we felt that it was important for users to also be able to organize and de-identify the data through the same tool. Our hope is that with the adoption of Trial Wire throughout the medical imaging world, we'll help our colleagues around the globe solve the most basic set of problems facing us today while also leading the way to greater innovation in other, more complex areas."

 

The easy-to-use interface is based on a series of pull-down menus and user prompts, which can be customized to user-specific, or trial-specific requirements. Trial Wire is now available online with the following features enabled:

 

1. Quick and simple setup - Using a simple web-based Java applet, Trial Wire requires no installation or hardware set-up and no dedicated computer. Simply register online for free, and within minutes you can begin to enjoy the benefits.

 

2 Easy de-identification - Set up the parameters for your trial and save your settings. De-identify standard tags and additionally ask Trial Wire to search for other potentially identifiable tags to alert you to.

 

3. Logical sort and structure - Read DICOM files from any directory and sort into Subject, Study, Series hierarchy. Output this new structure locally or transfer elsewhere.

 

4. Secure DICOM transfer with audit trail - Configure Trial Wire to transfer data to your secure FTP server after de-identification and organization. Print off the audit trail report for inclusion in the study folder.

 

The IXICO team will be demonstrating Trial Wire at ISMRM in Honolulu. Visit them at booth 322 to register for Trial Wire and receive a free gift. Or register for your free Trial Wire account today!
To find out more, visit http://www.mytrialwire.com. To learn about the wide range of IXICO products available visit http://www.ixico.com

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Stem cell therapy may cure blindness

The world's first stem cell therapy to cure the most common cause of blindness has been developed by British researchers.

 

The research team believes that the procedure, which can tackle age-related macular degeneration (AMD), will become a routine, one-hour method that will be generally available in six or seven years' time.

 

The treatment was pioneered by scientists and surgeons from the Institute of Ophthalmology at University College London and Moorfields eye hospital, and involves replacing a layer of degenerated cells with new ones created from embryonic stem cells, reports The Times.

 

In the new treatment, embryonic stem cells are transformed into replicas of the missing cells. They are then placed on an artificial membrane which is inserted in the back of the retina.

 

Tom Bremridge, chief executive of the Macular Disease Society, said: "This is a huge step forward for patients. We are extremely pleased that the big guns have become involved, because, once this treatment is validated, it will be made available to a huge volume of patients."

 

Laboratory trials completed by the British team, led by Professor Pete Coffey, director of the London Project to Cure Blindness, have demonstrated that stem cells can prevent blindness in rats with a similar disease to AMD.

 

Coffey said the treatment would take "less than an hour, so it really could be considered as an outpatient procedure. We are trying to get it out as a common therapy".

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Pharmacyclics announces Global Strategic Alliance with Les Laboratoires Servier

Pharmacyclics to maintain all US Rights

 

Conference Call to discuss the company's third quarter financial results is scheduled for April 23, 2009 at 11:00 a.m. EDT (8:00 a.m. PDT).

 

SUNNYVALE, Calif., April 17 /PRNewswire-FirstCall/ -- Pharmacyclics, Inc. (Nasdaq: PCYC) today announced that it has entered into a global strategic alliance with Servier, the leading French independent pharmaceutical company. The alliance will focus on the research, development, and commercialization of Pharmacyclics' PCI-24781, an orally active, novel, small molecule inhibitor of Pan HDAC enzymes, that is currently in Phase I/II clinical trials in the United States and being developed for the treatment of solid tumors and hematologic malignancies. Pharmacyclics expects that this alliance will enable it to aggressively pursue its goal of developing and commercializing its innovative anti-cancer Pan HDAC inhibitor agents.

 

"This alliance with Servier allows us to accelerate our productive discovery efforts, to expand our clinical development capabilities and potentially commercialize our unique and differentiated Pan HDAC inhibitor product outside of the United States in rapid fashion," said Robert W. Duggan, Chairman and Chief Executive Officer of Pharmacyclics. "We are honored to be partnering with the Servier Company, they are incredibly professional in all aspects of their business dealings. Their success and advancement of human healthcare is respected around the world."

 

Under the terms of the agreement, Servier acquired the exclusive right to develop and commercialize the Pan HDAC inhibitor product worldwide except for the United States and will pay a royalty to Pharmacyclics on sales outside of the United States. Pharmacyclics will continue to own all rights within the United States. Pharmacyclics will receive from Servier upfront payments totaling $11 Million on signing the contract and an additional guaranteed $4 Million for research collaboration over a 24 month period, paid in equal increments every 6 months with the initial payment due October 1, 2009. Servier will pay for all development costs outside the United States. In addition Pharmacyclics will receive $24.5 Million based on the achievement of certain milestones up to and including commercialization.

 

"The collaboration will focus on the clinical development of PCI-24781, as well as to support ongoing research and development of novel, increasingly selective HDAC inhibitors and gives us the opportunity to rapidly bring to market innovative, best-in-class treatments for cancer patients," said Dr. Maky Zanganeh, Vice President of Business Development for Pharmacyclics.

 

"The combination of Servier's outstanding clinical team with Pharmacyclics' research expertise in novel, small molecule inhibitors of Pan HDAC enzymes, presents a unique opportunity to develop this exciting new class of drugs to its full therapeutic potential," said Dr. Joseph J. Buggy, Vice President of Research for Pharmacyclics.

 

Pharmacyclics also announced today it will hold a conference call to announce its third quarter fiscal 2009 financial results and achievements. The call is scheduled for April 23, 2009, at 11:00 a.m. EDT (8:00 a.m. PDT). To participate in the conference call, please dial 866-727-3220 for domestic callers and 706-643-1591 for international callers. The conference ID is 95994112. To access the audio broadcast or the subsequent archived recording, log on to http://www.pharmacyclics.com. The archived version of the webcast will be available on the company's website for one month.

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Array BioPharma's ARRY-614 Demonstrates Cytokine Inhibition and Anti-Tumor Activity in Preclinical Models of Hematological Cancers

Phase 1 and Preclinical Data Support Further Clinical Study of ARRY-614 in Hematological Cancers

 

Array BioPharma Inc. has announced the presentation of an abstract detailing positive data for its novel, small-molecule p38 / Tie2 inhibitor, ARRY-614. In this study, ARRY-614 demonstrated the potential for potent inhibition of cytokine synthesis, including IL-6 and TNF, and anti-tumor activity in hematological cancers. The data was presented at the American Association for Cancer Research (AACR) 100th Annual Meeting. The complete poster is available as a PDF on Array's website at www.arraybiopharma.com.

 

"The p38 MAP kinase is a modulator of apoptosis and survival pathways as well as an important regulator of cytokine production," said Kevin Koch, Ph.D., President and Chief Scientific Officer. "Up-regulation of cytokine levels has been implicated in cancer progression. We believe p38 inhibitors may have significant anti-tumor effect by inhibiting these key cytokine signals. ARRY-614 has demonstrated potent inhibition of cytokines in Phase 1 healthy subject studies. Data presented here supports the use of ARRY-614 for the treatment of cytokine-dependent, hematological malignancies, including myelodysplastic syndromes (MDS) and multiple myeloma, with an additional opportunity in certain cytokine-dependent solid tumor indications."

 

Abstract # 331 (April 19, 8:00 a.m.; Hall B-F, Poster Section 12): "Activity of ARRY-614, an inhibitor of p38 map kinase and angiogenic targets, in hematologic malignancies" details the inhibitory activity of ARRY-614 against p38 MAPK and Tie2/Tek receptor tyrosine kinase in relevant preclinical models at well-tolerated doses. ARRY-614 demonstrated activity both as a single agent and in combination with Revlimid® (lenalidomide).

 

Results show that ARRY-614 was well-tolerated and effective in inhibiting cytokines, including IL-6 and TNF, which play a role in the regulation of growth and survival in a number of cancers, particularly hematological cancers. As a single agent, ARRY-614 effectively inhibited angiogenesis in vivo and inhibited tumor growth in preclinical models of multiple myeloma. Additionally, data show that administering p38 inhibitors in combination with lenalidomide yielded superior inhibition of proinflammatory cytokines and combining ARRY-614 with standard-of-care agents, lenalidomide and Decadron® (dexamethasone) in multiple myeloma provided additional anti-tumor effects.

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Dendreon Announces Data on PROVENGE Potency and Long-Term Immune Responses in Androgen-Dependent Prostate Cancer

Researchers from Dendreon Corporation presented today data from its PROTECT (PROvenge Treatment and Early Cancer Treatment) or P-11 Phase 3 study suggesting that PROVENGE(R) (sipuleucel-T) induces long-term memory immune responses that are durable and can be maintained following boosting. The results of the study also indicate that CD54 upregulation on Antigen Presenting Cells (APCs), a measure of potency, is a correlate of immune activation.

 

P-11 is an ongoing Phase 3 clinical trial designed to evaluate the safety and biologic activity of PROVENGE in patients with non-metastatic androgen-dependent (hormone sensitive) prostate cancer who have had a prostate-specific antigen (PSA) recurrence following surgical removal of the prostate. Patients were randomized to PROVENGE or placebo following 3 months of hormone therapy. This study evaluated CD54 upregulation and peripheral immune responses in men enrolled in the trial.

 

PROVENGE or placebo was administered at weeks zero, two and four. A treatment booster infusion of PROVENGE or placebo was offered after confirmed PSA greater than or equal to 3.0ng/mL. Immune responses were measured pre-treatment, at weeks four and 13, and at four and 13 weeks following the booster infusion.

 

At the week zero dose of PROVENGE, the expression of CD54 on APCs was upregulated 5.8 fold. At the week two dose, it was 10.1 fold, significantly increased from week 0 (p < 0.001). The increase in CD54 upregulation persisted at week four (10.7 fold) and at the time of the booster infusion (12.0 fold). There was an increase in cellular immune response between pre-treatment and week four (p < 0.001), which persisted through 13 weeks after the booster infusion (p < 0.001). The PROVENGE booster infusions occurred from 0.2 to 5.5 years (median 1.1 years) after the week four dose.

 

Data is being presented in a session titled, "Cancer Vaccines: Human Studies" in a presentation titled, "Antigen presenting cell activation in sipuleucel-T and long-term immune responses in prostate cancer trial" today at 8:00 AM MDT at the 100th Annual Meeting of the Association for Cancer Research in Denver, Colorado.

 

"We are encouraged to see that CD54 upregulation in APCs is maintained after boosting in men with androgen-dependent prostate cancer," said David Urdal, chief scientific officer of Dendreon. "This pattern of CD54 upregulation suggests that the first dose 'primes' the immune system for subsequent 'memory' responses and is consistent with that observed in our studies of men with androgen-independent disease where the cumulative CD54 upregulation dose correlated with survival. We also are encouraged by these data which suggest that the immune response generated by PROVENGE is durable for a year or more after initial treatment and that it can be maintained following boosting."

 

Study Design

 

The study, known as PROTECT (PROvenge Treatment and Early Cancer Treatment) or P-11, is a randomized, double-blind, placebo-controlled trial designed to evaluate the safety and biologic activity of PROVENGE in men with non-metastatic androgen-dependent prostate cancer who have had a prostate-specific antigen (PSA) recurrence following surgical removal of the prostate. A total of 176 patients at 19 sites in the United States were randomized two to one to receive PROVENGE or placebo following a three-month course of hormonal therapy. Patients were then followed with serial PSA measurements to evaluate the impact of PROVENGE on PSA and PSADT (PSA doubling time). At the time of biochemical progression, defined as a PSA of 3 ng/mL or greater, men became eligible for one booster infusion of either PROVENGE or placebo in accordance with the treatment arm to which they were randomized. Patients continue to be followed for the clinical endpoints of time to distant failure, which typically would be the appearance of a positive bone scan, and for overall survival.

 

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New therapeutic target for pancreatic cancer found

A research team led by Indian origin scientist has identified a potential target for pancreatic cancer, one of the most fatal cancers.

 

Akhilesh Pandey, a Johns Hopkins University pathologist has identified an epidermal growth factor receptor, which has found to be aberrantly active in approximately a third of the 250 human pancreatic cancers studied.

 

The team has found a phosophorylated epidermal growth factor receptor (pEGFR), which is closely related to HER-2, a growth factor receptor found and used as a drug target in a subset of breast cancers.

 

After he found and profiled the pEGFR activated in the pancreatic cancers, Dr. Pandey realized the same receptor had been found by other researchers to be activated in a subset of lung cancers.

 

And, most promising, an EGFR inhibitor named erlotinib is used for treatment of these specific lung cancers.

 

During the research, the researchers used mice in which human pancreatic tumour cells with activated EGFT had been placed. The tumours began growing.

 

But when treated with erlotinib, they began to shrink. Other tumours without activated pECFR showed no response.

 

Dr. Pandey said that the promise - and the challenge - of using pEGFR is that of personalized medicine.

 

Earlier studies in other laboratories and clinical trials already had tried EGF inhibitors as a treatment for pancreatic cancer and concluded that they did not work.

 

However, when Dr. Pandey's collaborators allowed them to re-examine their samples, they found that the only case in 12 cases that had responded to the EGF inhibitor was the only case with an activated EGF receptor.

 

Dr Pandey plans to use mass spectrometry to find additional markers of pancreatic cancer in the tumours themselves but also in blood and urine, which would avoid the problems of invasive biopsies.

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Clinical Trials Update for April 2009

Restless Leg Syndrome (RLS) Depression Rheumatoid Arthritis Healthy Patient Studies Chronic Leg Pain Women's Health

(HealthDay News) -- Here are the latest clinical trials, courtesy of ClinicalConnection.com and CenterWatch:

Restless Leg Syndrome (RLS)

This study seeks qualified participants with restless leg syndrome.

The research site is in DeLand, Fla.

More information

Please see http://www.clinicalconnection.com/clinical_trials/condition/restless_legs.aspx.  

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Depression

If you are 65 or older and have had symptoms of depression for at least four weeks, you may qualify for this study of an investigational medication.

The research site is in Cherry Hill, N.J.

More information

Please see http://www.clinicalconnection.com/clinical_trials/condition/depression.aspx.

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Rheumatoid Arthritis

If you have been diagnosed with rheumatoid arthritis and are not getting adequate relief from your current treatment regimen, you may qualify for this study of an investigational medication.

The research site is in San Antonio, Texas.

More information

Please see http://www.clinicalconnection.com/clinical_trials/condition/arthritis.aspx.

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Healthy Patient Studies

If you are a healthy adult aged 18 to 55, you may qualify for this study.

The research site is in Neptune, N.J.

More information

Please see http://www.centerwatch.com/clinical-trials/listings/studylist.aspx?CatID=361.

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Chronic Leg Pain

If you are aged 30 to 70, have moderate-to-severe chronic lower leg pain associated with lumbar disc herniation, and have had no improvement after conservative non-surgical treatment, you may qualify for this study.

The research site is in Detroit, Mich.

More information

Please see http://www.centerwatch.com/clinical-trials/listings/studylist.aspx?CatID=304.

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Women's Health

If you are a postmenopausal woman aged 50 or older, you may qualify for this study.

The research site is in Missoula, Mont.

More information

Please see http://www.centerwatch.com/clinical-trials/listings/studylist.aspx?CatID=438.

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Chiltern Acquires Brazil-Based Clinical Research Organization Vigiun

 Chiltern International Limited (Chiltern), a global Clinical Research Organization (CRO) providing clinical development and staffing services in Europe, the Americas and India, today announced the acquisition of Vigiun, a full service Clinical Research Organization located in Sao Paulo, Brazil.

 

Established in 1999 by Eduardo Forleo, MD, and Elisa Halker, BSN, Vigiun has extensive experience conducting clinical trials in a variety of therapeutic areas, in particular infectious disease, oncology, and respiratory.

 

"We warmly welcome Vigiun to the Chiltern team," stated John Vann, Executive Vice President, Americas. "The acquisition of Vigiun enhances Chiltern's growing presence in Latin America, which was established nearly a year ago when we began operations in Argentina under the leadership of Oscar Podesta, our General Manager for Latin America. The knowledge and experience of Eduardo Forleo and Elisa Halker, and all of the Vigiun staff, will further strengthen our ability to serve our clients and continue our strategy for growth in the region."

 

Dr. Forleo has been appointed Chiltern's Country Manager for Brazil and Medical Director for Latin America. Ms.Halker will serve as Director of Clinical Operations for Brazil.

 

Said Dr. Forleo, "This is an exciting time to become a part of Chiltern. Our business has grown to the point that it makes sense to join forces with a global CRO whose mission and values align with ours. I look forward to contributing in very positive ways to the company's ongoing and future success."

 

"I am very pleased to have Vigiun join Chiltern," said Glenn Kerkhof, Chiltern's CEO. "Vigiun is an ideal complement to our existing Latin American operations and Chiltern's presence in 27 other countries as we serve the pharmaceutical and biotech industries globally."

 

Latin America has a population of 503 million people, of which 192 million are in Brazil. This vast population provides a significant number of potential patients in all disease areas. Latin America is rich with experienced investigators and is known for high quality data and excellent patient retention in clinical trials.

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GlaxoSmithKline, Pfizer join to fight HIV

When we hear of pharmaceutical companies' ventures it's usually either a straight merger & acquisition or a collaboration on a drug or two in their pipelines to share costs and, of course, potential profits. But Pfizer Inc. (PFE) and GlaxoSmithKline (GSK) have come up with a new one.

 

Rather than merge (recall, Pfizer is acquiring Wyeth for $68 billion), or collaborate on a drug or two, the two have decided to merge their HIV operations. They plan to develop a company focused solely on research, development and commercialization of HIV medicines.

 

Glaxo is currently one of the biggest sellers of HIV treatments, but its drugs are older, with some coming off patent as soon as 2012. With its sales falling and its pipeline weak, it makes sense to combine operations with Pfizer, which has a more robust HIV pipeline. Together, they claim, they will have 19 percent market share.

 

Glaxo will initially hold an 85 percent equity interest in the new company, leaving Pfizer with the other 15 percent, but this could change depending on milestones achieved. The new company will have 11 marketed products, including Combivir, Kivexa and Pfizer's Selzentry/Celsentri, which together generated sales in 2008 of £1.6 billion ($2.4 billion). The venture will also have a pipeline of 6 medicines, including four in phase II development. The new company could be worth $7.5 billion, according to the Wall Street Journal.

 

During these hard times, drug companies are not only facing a recession and the need to control costs better, but many of the Big Pharma blockbuster revenue producing drugs are coming off patent. Andrew Witty, Glaxo's CEO, has often said he is not interested in mega-mergers, but rather these kinds of deals that can "create value and generate efficiency."

 

Could this indeed be a sign of new deals to come? Instead of large M&As to create mega-companies, could we see the joining of forces to actually create smaller, specialized ones? In terms of deal making, this is indeed an innovation, but it remains to be seen how well it will do.

 

The HIV drug business is a tough area of drug development and both companies faced pressure in the segment. There are only a few dozen good treatments available, and coming up with something better has often proved difficult. Pfizer and Glaxo's collaboration is indeed an attempt to breathe life into a challenging product segment. The new company will have the resources from their combined revenue for dedicated research, so that it could maybe lead to the development of more medicines, more efficiently, which could lead to more people living with HIV/AIDS.

 

Gilead Sciences (GILD), which now dominates the HIV drug market, along with Bristol Myers Squibb (BMY) have hurt Glaxo's sales. But if the new company will be as innovative and creative in its drug development as it has been in its business model, perhaps it could present a welcome challenge to current rivals, because that's what's really important at the end of the day -- the development of new effective drugs.

 

According to the UNAID, an estimated 33 million people were living with HIV in 2008, of whom about four million were taking HIV/AIDS medications. In 2008, the market for HIV medications was worth about $12.3 billion and it is growing as people live longer. There is no cure for the human immunodeficiency virus (HIV) that causes AIDS, but combinations of drugs can keep the virus from replicating and damaging the immune system.

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Glaxo, Pfizer Join to Create New Drug Company

In the hope of cutting costs and mitigating the risks of research into new treatments, pharmaceutical giants GlaxoSmithKline PLC and Pfizer Inc. will pool resources to create a new company.

 

Announced Thursday, the deal is the result of declining revenues and companies in an attempt to reduce the cost factor are teaming up with competitors to share the risks and costs of developing new drugs. In this collaboration of the world's two biggest drug companies, London-based Glaxo will team up with New York-based Pfizer to create a "more sustainable" organization.

 

The companies plan to merge their HIV operations into a new company and they said that the new HIV business would be more sustainable and broader in scope than either individually, with the potential for cost savings by melding the commercial operations.

 

"What you are seeing is an industry facing the realities of the challenges that exist and also, to some degree, a new generation of management being prepared to come forward with different solutions," said Glaxo Chief Executive Andrew Witty.

 

The new company will be based in London and run by Glaxo executive Dr. Dominique Limet, now head of its personalized medicine strategy. In the U. S. the headquarters will be in Research Triangle Park, N. C., with Glaxo's American headquarters.

 

Witty said they expected savings of $90 million, or 60 million pounds from cutting administration and marketing overlaps while the research and development operations would remain unchanged.

 

"The combination of a broad current revenue base and a new diverse pool of pipeline assets provide a significant platform to invest in developing and delivering new HIV medicines," Witty told analysts during a conference call.

 

He added that the new company will maintain "not-for-profit pricing" of AIDS drugs in needy countries and will continue community support and AIDS prevention programs. In Glaxo's existing HIV drugs some are with patents near expiration while Pfizer has a better range of drugs in development. Analysts have noted that Glaxo's HIV drug sales have not risen with the current market trend of 14 % shown last year.

 

In the new company Glaxo will hold an 85 % interest while Pfizer will hold 15 % and the stakes will increase or decrease depending on which company produces more successful drugs. The new venture will have a 19 % market share, just behind leader Gilead Sciences Inc. and will have several market-leading therapies, including Combivir, Epzicom/Kivexa and Pfizer's Selzentry/Celsentri.

 

The company will have an initial capitalization of about $373 million, or 250 million pounds, 90 % from Glaxo. Witty said the new company can later ask its board of seven executives from Glaxo and two from Pfizer, for more funding.

 

"It's going to have two parents out there with, I think, a very rapid decision-making mechanism to allow it to be funded for what it needs to do," he said. "It will also have the flexibility to do other deals and license in other (drugs)."

 

The company will have six drugs in human testing, four in mid-stage tests, and a total of 17 experimental compounds with a key goal to develop drugs that overcome resistance to the HIV virus, in combination pills.

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Clinical trials not just for drugs

Clinical trials are a vital part of a new drug's progress toward approval for widespread use. And it's not just drugs that go through trials; the Food and Drug Administration, the agency with oversight, says a trial might also be for a medical device, or biologic, such as a vaccine, blood product, or gene therapy.

In any case, trials must be thoroughly reviewed before commencing and monitored through their duration in order to protect the health and welfare of volunteers.

The FDA notes that the risks to volunteers may vary depending on the treatment being studied and the health of the people participating in the trial. All known risks must be fully explained by the researchers before the trial begins.

The FDA 'requires that potential participants be given appropriate information about the study to enable them to decide whether to enroll in the clinical trial. This process is known as `informed consent,' and it must be in writing,'' says the agency's website, fda.gov.

Learn more about clinical trial procedures and how to volunteer here.

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Pharmacyclics Updates Positive Clinical Responses in its PCI-24781 Clinical Program Targeting HDAC

Pharmacyclics, Inc. has  today announced an update to its clinical programs targeting histone deacetylase (HDAC) with its drug candidate PCI-24781 that is currently in multiple clinical trials for treating various solid and hematologic tumors. In addition, the Company announced multiple presentations regarding its orally available HDAC inhibitor compound at the annual AACR meeting in Denver, Colorado.

 

HDAC inhibitors induce differentiation of cancer cells and block cancer cell proliferation at non-toxic concentrations. PCI-24781 is a novel, potent, orally active small molecule inhibitor of HDAC enzymes with anti-tumor activity in a variety of preclinical tumor models (Buggy et al Mol Cancer Ther 2006; 5 (5), p. 1309-1317) and is synergistic with many cancer chemotherapeutic agents. PCI-24781 has an optimized half life, oral bioavailability, potency, and duration of exposure to achieve an ideal balance of efficacy with minimal toxicity.

 

In a preliminary data review, PCI-24781 is showing promising response in ongoing Phase I/II trials in refractory lymphoma and solid tumors, and is planned to be tested in an upcoming chemotherapy combination setting trial this summer. Currently 16 patients have been enrolled to date in a multicenter Phase I/II monotherapy trial in refractory lymphoma. From 10 patients evaluated to date, PCI-24781 has shown good activity (70% PR+SD) as a single agent, with one partial response in follicular NHL and verified stable diseases in SLL, CTCL, Hodgkin's disease and follicular lymphoma. In addition, one patient with angioimmunoblastic T-cell lymphoma had a resolution of multiple disease lesions except for one lesion, but was overall scored as a disease progression. In refractory solid tumors where 44 patients have been enrolled in IV and oral dose escalation trials, there were 8 SD out of 31 evaluable patients. Overall duration of SD was very good, with the longest duration (8 months) observed in a rectal adenocarcinoma patient. To date, PCI-24781 has been well tolerated by 60 patients and has demonstrated an excellent safety profile with no significant cardiotoxicities or fatigue.

 

"PCI-24781 is an important HDAC inhibitor which is differentiating itself in the HDAC competitive space by virtue of lack of serious side effects such as QTc prolongation and severe fatigue frequently observed with other HDAC inhibitors. I am impressed with its therapeutic window and the quality of this overall drug development program to date," said Dr. Edward Sausville, M.D. Ph.D., former Associate Director of the Division of Cancer Treatment and Diagnosis for the Developmental Therapeutics Program at the National Cancer Institute and member of the Pharmacyclics Scientific Advisor Board. Dr. Sausville is currently Professor of Medicine, Associate Director of the Division of Cancer Treatment and Diagnosis for the Developmental Therapeutics Program and Director of Research, University of Maryland Greenebaum Cancer Center.

 

The scientific presentations will take place at the 100th Annual Meeting of the American Association of Cancer Research, being held at the Colorado Convention Center in Denver, CO from April 18-22, 2009. The presentations will include a seminar regarding the identification of micro-RNA and mRNA biomarkers of response to PCI-24781 in primary colon tumors and tumor cell lines. This work is being done with a view to preselecting patients most likely to respond to PCI-24781 in a future Phase II clinical trial. A second presentation details the therapeutic efficacy of this compound in a mouse model of gallbladder carcinoma, which is correlated with the down regulation and translocation of erbB2, an EGFR family member. A third presentation shows that increased superoxide level is a biomarker of PCI-24781 activity in patients receiving this compound. In leukemia cells, PCI-24765 can lead to increased oxidative stress leading to caspase-8-dependent apoptosis.

 

The presentations and published abstracts are as follows:

 

Tuesday, April 21, 2009
Time: 1:00 pm - 5:00 pm
Poster Presentation
Abstract #4548 PCI-24781, a novel hydroxamic acid HDAC inhibitor, induces apoptosis and histone acetylation in a caspase-8 dependent manner in leukemia cells Nilsa Rivera-Del Valle, Shan Gao, Xiaolin Lu, Mint Sirisawad, Susanne Steggerda, Sriram Balasubramanian, Jennifer Wheler, Joya Chandra.
University of Texas MD Anderson Cancer Ctr., Houston, TX & Pharmacyclics Inc, Sunnyvale, CA
Poster Session : Agents Targeting Histone Deacetylases and DNA Methyltransferase
Location: Hall B-F, Poster Section 32 Poster Board Number 6

 

Tuesday, April 21, 2009
Time: 1:00 pm - 5:00 pm
Poster Presentation
Abstract #4549 The inhibitory effects of the histone deacetylase (HDAC) inhibitor, PCI-24781, alter growth of gallbladder cancer cells and downregulate erbB2 expression Kaoru Kiguchi, Takuya Kitamura, Tetsuo Ajiki, Kevin Connolly, John DiGiovanni.
University of Texas M.D. Anderson Cancer Ctr., Smithville, TX & Kobe University Graduate School of Medicine, Kobe, Japan
Poster Session : Agents Targeting Histone Deacetylases and DNA Methyltransferase
Location: Hall B-F, Poster Section 32 Poster Board Number 7

 

Wednesday, April 22, 2009
Time: 8:30 am - 12:00 pm
Oral Presentation: 8:40 am - 8:55 am
Abstract #5630 Identification of micro-RNA markers of response to HDAC inhibitor PCI-24781 in primary colon tumors Sriram Balasubramanian, Mint Sirisawad, Miriana Moran, Hannah Mamuszka, Joseph J. Buggy. Pharmacyclics, Inc., Sunnyvale, CA & Oncotech, Tustin, CA
Session: Minisymposium - Histones, Tubulin, and Proteasome Targets
Location: Room 505-507, Colorado Convention Center

 

All abstracts are currently available online at http://www.aacr.org/

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Icagen Presents Results of Phase I Program of ICA-105665

Icagen, Inc. has today presented results of the Company's Phase I program for ICA-105665, the Company's lead drug candidate for the treatment of epilepsy and neuropathic pain, at the Antiepileptic Drug Trials X Conference in Coral Gables, Florida.

As the initial study in the Phase I program, a single ascending dose trial of ICA-105665 was conducted in healthy volunteers. Nine cohorts of healthy volunteers, each consisting of six subjects receiving study medication and three subjects receiving placebo, were studied at doses ranging from 30mg to 400mg administered orally. Following this study, the Company then conducted a multiple ascending dose clinical trial of ICA-105665. Three cohorts of healthy volunteers, each consisting of six subjects receiving study medication and two subjects receiving placebo, were studied at doses of 50mg, 100mg and 200mg administered orally twice daily for a period of seven days. Following completion of the three cohorts of healthy volunteers, the multiple ascending dose study was expanded to include patients with epilepsy. Two cohorts, comprised of a total of fourteen patients, were studied at doses of 100mg or 200mg administered orally twice daily for a period of seven days. All epilepsy patients were also concurrently receiving one anti-epileptic drug.

In both studies, plasma concentrations in excess of predicted efficacious concentrations were achieved. The compound was well tolerated at all dose levels, and a maximum tolerated dose was not identified. There were no serious adverse events, no dose limiting toxicities, and no dropouts. There were also no clinically significant changes in laboratory values and no effects on any electrocardiogram parameters, including the QT interval. Adverse events related to the central nervous system were mild and consistent with those of other anti-epileptic drugs.

In both studies, pharmacokinetics were linear, dose proportional, and consistent with the potential for twice daily dosing. Over a seven day period, ICA-105665 did not appear to have any effect on the plasma concentrations of other anti-epileptic drugs. Other anti-epileptic drugs that are not hepatic enzyme inducing did not affect plasma concentrations of ICA-105665. Enzyme inducing anti-epileptic drugs decreased the exposure levels of ICA-105665.

As previously reported, ICA-105665 was recently placed on partial clinical hold for epilepsy due to findings in certain high dose preclinical studies. The Company is in the process of conducting additional preclinical studies to address the issues raised by the FDA. Proof-of-concept studies for both epilepsy and pain are in the planning stages.

Seth V. Hetherington, SVP Clinical and Regulatory Affairs, noted, "We are pleased with the results of this Phase I program. ICA-105665 was well tolerated by both healthy volunteers and patients with epilepsy at a wide range of doses from 30 to 400mg total dose each day. We look forward to studying this selective KCNQ opener in future clinical studies."

 

 

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GlobeImmune starts cancer drug trial

GlobeImmune Inc. has started a clinical trial to investigate the safety and tolerability of a new drug for patients with metastatic cancers.

 

The company hopes Tarmogen, GI-6207, will treat certain metastatic cancers, types of cancer that spread from one part of the body to another. This is the third Tarmogen product candidate to enter human clinical trials over the last four years.

 

Dr. James L. Gulley, director of the Clinical Trials Group LTIB at the National Cancer Institute, will be the principal investigator for the Phase I study funded by the institute.
.
Dr. Timothy Rodell, president and chief executive of GlobeImmune, said Tarmogens are designed to activate the immune system to recognize and attack cells with disease-specific characteristics such as carcinoembryonic antigen, a protein associated with tumors and the developing fetus. The trial will build on the company's previous trials targeting pancreas and colon cancers.

 

Last year, GlobeImmune signed a cooperative research and development agreement with the institute and National Institutes of Health to jointly develop multiple product candidates intended to treat a variety of cancers. Carcinoembryonic antigen is the first cancer antigen to be targeted in human trials through the collaboration.

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Medtronic commences abdominal aortic aneurysm stent graft study

Medtronic, Inc. has announced the start of ENGAGE, the largest ever study of its kind, which will evaluate the performance of the Endurant stent graft, an implantable medical device designed to provide an advanced minimally-invasive alternative to open surgical repair of abdominal aortic aneurysms.

 

"ENGAGE seeks to involve more patients, at more sites and in more countries than any previous study of its kind," according to Dr. Robert Fitridge of The Queen Elizabeth Hospital in Adelaide, Australia, one of the study's seven executive committee members. "The data this multicenter international study collects on the Endurant stent graft will help physicians worldwide determine how best to treat abdominal aortic aneurysms in the real-world setting of standard clinical practice."

 

Fitridge led the team that enrolled the first patient in this global post-market study on March 24. The other six ENGAGE executive committee members include: Drs. Dittmar Böckler of the University of Heidelberg in Germany; Paul Hayes of Addenbrookes Hospital in Cambridge, England; Furuzan Numan of Memorial Hospital in Istanbul, Turkey; Juan Carlos Parodi of FLENI in Buenos Aires, Argentina; Vicente Riambau of Hospital Cl?co de Barcelona in Spain; and Yehuda Wolf of Sourasky Medical Center in Tel-Aviv, Israel.

 

"Around half of aortic repair procedures are currently performed using endovascular stent grafts. The ENGAGE study is designed to provide clinicians with enhanced confidence in the performance and ease of use of the Endurant stent graft, so even more patients benefit from a life-saving procedure without the need for open surgery," said Tony Semedo, vice president of CardioVascular and general manager of the Endovascular Innovations division at Medtronic.

 

ENGAGE is expected to enroll 1,200 patients with abdominal aortic aneurysms at up to 80 medical centers across six continents. Patients who meet the single-arm study's inclusion criteria will be treated with the Endurant system and followed for five years. The study's primary endpoint is treatment success at 12 months. Treatment success is a composite endpoint which requires the satisfaction of several criteria. These criteria include successful technical delivery and deployment of the stent graft as well as freedom from: aneurysm swelling; endoleaks; aneurysm rupture; conversion to surgery; graft migration; and graft occlusion.

 

The Endurant stent graft system expands Medtronic's portfolio of aortic repair technologies, which offer physicians a broad array of devices to choose from in treating patients with aortic aneurysms. It received Conformité Européene mark in July 2008 and is now commercially available in more than 80 countries. Use of the Endurant stent graft system in the United States is limited to an investigational clinical trial.

 

 

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Osiris Completes Enrollment in Second Prochymal Phase III Trial for Graft vs. Host Disease

Osiris Therapeutics, Inc. today announced that it has successfully completed patient enrollment in its pivotal, Phase III trial evaluating Prochymal as a first-line treatment for acute graft vs. host disease (GvHD), a life-threatening complication of bone-marrow transplantation. The double-blind, placebo-controlled trial enrolled 190 patients from 52 leading transplant centers across the United States, Canada and Australia. Osiris has now completed enrollment in two pivotal stem cell trials in GvHD and expects top-line data from both studies in the second half of 2009.

 

Additionally, the company announced that it has confirmed with the U.S. Food and Drug Administration, receipt of the first portions of its Biological License Application or BLA for Prochymal as part of a rolling submission. A BLA is a comprehensive regulatory submission prepared by a biologic drug's sponsor to obtain full marketing approval from the FDA. Rolling submission is an FDA provision available to drug candidates that have received Fast Track designation, which allows for completed sections of a BLA to be submitted on an ongoing basis. It can facilitate the process by allowing FDA to initiate review of sections as soon as they are available.

 

About the Phase III Acute GvHD Trial

The Phase III double-blind, placebo controlled trial will evaluate the safety and efficacy of Prochymal in conjunction with steroid therapy in patients with newly diagnosed acute GvHD, grades B-D. The target enrollment for the trial was 184 patients. The primary endpoint of the trial is the proportion of patients surviving at least 90 days that achieve a complete response when Prochymal is added to steroid therapy as compared to those receiving steroids alone. Patients are considered treatment failures if they do not achieve a complete response within 28 days of initiating treatment, if the steroid dose is increased or other immunosuppressive agents are added, or if the patient does not survive 90 days following initial treatment.

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Gilead Initiates Phase II Clinical Trial of Integrase-Based, Single-Tablet, Once-Daily Regimen for the Treatment of HIV

Gilead Sciences, Inc. today announced that it has begun enrolling patients in a Phase II clinical trial of its investigational integrase-based, single-tablet, once-daily regimen of elvitegravir, GS 9350 and Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) for the treatment of HIV-1 infection. GS 9350 is an investigational compound being developed as a pharmacoenhancing or "boosting" agent to increase blood levels and allow once-daily dosing for certain medicines, including Gilead's investigational HIV integrase inhibitor, elvitegravir. The Phase II study is designed to evaluate the safety and efficacy of the regimen compared to once-daily Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg). The study will enroll 75 HIV-1 infected, antiretroviral treatment-naïve adults across approximately 50 investigative sites in the United States.

 

About the Phase II Study

The Phase II study is a randomized, double-blind, 48-week clinical trial that will evaluate the safety and efficacy of a single-tablet containing elvitegravir, GS 9350 and Truvada versus Atripla, each administered in HIV-infected treatment-naïve adults with HIV RNA levels (viral load) greater than or equal to 5,000 copies/mL and CD4 cell counts greater than 50 cells/mm3. Entry criteria require that patients do not have nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor or primary protease inhibitor resistance mutations, as defined by International AIDS Society-USA guidelines, and no prior use of antiretroviral treatments.

 

Seventy-five trial participants will be randomized (2:1) to receive a once-daily tablet containing elvitegravir 150 mg/GS 9350 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (n=50) or Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) (n=25).

 

The primary endpoint will be the proportion of patients with viral loads less than 50 copies/mL at 24 weeks of treatment. Secondary endpoints will include the proportion of patients with viral loads less than 50 copies/mL at 48 weeks of treatment, and the safety and tolerability of the two treatment regimens through 48 weeks of treatment.

 

After week 48, subjects will continue to take their blinded study drug until treatment assignments have been unblinded, at which point all subjects will be given the option to participate in an open-label rollover extension and receive the single-tablet regimen containing elvitegravir, GS 9350 and Truvada.

 

 

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GlaxoSmithKline and Pfizer announce innovative agreement to create a new world-leading, specialist HIV company

    *  Creates a new focused HIV business with the independence and sustainability to deliver significant improvements in treatment, access and shareholder value
    * Renews focus on HIV with industry-leading pipeline to deliver more new HIV treatments
    * Equity split of 85% GSK and 15% Pfizer

 

GlaxoSmithKline plc (GSK) and Pfizer Inc (PFE) today announced they have entered into an agreement to create a new world-leading HIV company focused solely on research, development and commercialisation of HIV medicines. The new HIV business will be more sustainable and broader in scope than either company's individually, and will hold a 19% share of the growing market and have an industry-leading pipeline.  GSK will initially hold an 85% equity interest in the new company and Pfizer will hold 15%.

 

Andrew Witty, Chief Executive Officer, GSK said: "Today marks a definitive step by GSK to renew our focus and deliver more medicines, more efficiently, to people living with HIV/AIDS. At the core of this specialist business is a broad portfolio of products and pipeline assets, which can be more effectively leveraged through the new company's strong revenue base and dedicated research capability. HIV remains a global threat with increasing incidence and viral resistance. This new company will be better placed to meet these challenges and improve access to treatments."

 

Jeff Kindler, Chief Executive Officer, Pfizer said: "By combining Pfizer's and GlaxoSmithKline's complementary strengths and capabilities, we are creating a new global leader in HIV and reaffirming our ongoing commitment to the treatment of the disease. With the strength of the companies' current HIV products, as well as the complementary fit of Pfizer's HIV pipeline and GSK's global distribution capabilities, the new company is well positioned to bring new and improved medicines to patients with more speed and efficiency. The new company can reach more patients and accomplish much more for the treatment of HIV globally than either company on its own."

 

Focused new business with industry-leading HIV pipeline
The new company will have a broad product portfolio of 11 marketed products including market-leading therapies such as Combivir, Kivexa and Selzentry/Celsentri. Based on 2008 pro-forma results, this combined portfolio generated sales of approximately £1.6 billion and these revenues will provide the new company with financial stability and support investment in its pipeline.

 

The clear focus of the new business will be to invest in research and development of innovative HIV treatments and formulations that improve adherence and overcome resistance to the virus.

 

The company will have an industry-leading pipeline of 6 innovative and targeted medicines, including 4 compounds in phase II development. Altogether, the new company will have 17 molecules at its disposal to develop in fixed-dose combinations as possible new HIV treatments. The new company will contract R&D services directly from GSK and Pfizer to develop these medicines.

 

The new company will also invest in early-stage research and discovery of HIV medicines, and will benefit from a new Research Alliance Agreement with GSK and Pfizer. Under this new alliance, GSK and Pfizer will continue to conduct discovery research and development into HIV medicines and the new company will invest in this activity and will have exclusive rights of first negotiation in relation to any new HIV-related medicine developed by either GSK or Pfizer.

 

More info available at the following URL: http://www.gsk.com/media/pressreleases/2009/2009_pressrelease_10041.htm

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Medifocus Inc. Reports Improved Clinical Efficacy for its Phase II, Randomized Clinical Study for the Treatment of Early Stage Breast Cancer Tumors

Medifocus Inc. announced that positive clinical results when using the Company's proprietary focused heat treatment prior to surgery for the treatment of early stage breast cancer tumors, were presented during the Market Opening Ceremony of Medifocus at the Toronto Stock Exchange on March 25, 2009 and also at the 19th National Interdisciplinary Breast Center Conference held March 14-18, 2009 in Las Vegas, Nevada. The patient data were obtained from a multi-center, randomized clinical study to reduce cancer cells at the surgical margins, which potentially can reduce either re-excisions rates or second incision rates when Medifocus's focused heat, is delivered prior to surgery. This study was conducted in the USA under an Investigational Device Exemption (IDE) issued by the Food and Drug Administration (FDA). The data presented at the 2009 National Interdisciplinary Breast Center Conference represent the final analysis of the clinical data for the focused heat treatment for early-stage breast cancer. Dr. William C. Dooley, MD, at the University of Oklahoma, Health Sciences Center, was the Principal Investigator of the multi-institutional study that was conducted at 10 breast centers in the United States and the United Kingdom.

 

The primary treatment modality for the treatment of early stage breast cancer is surgery. For early stage breast cancer, if the tumor is detected early enough, and the tumor is small enough, then a breast conservation surgery (BCS) known as lumpectomy could be offered. One of the biggest concerns for lumpectomy is positive tumor margins, which normally will require either re-excision or second incision to remove the remaining cancer cells. In addition, clinical studies indicate that if the surgery is performed and the margin is positive with cancer cells, then there is an estimated 500% increase in the chance for recurrence of the breast cancer compared to when the margins are negative. The reported clinical trial results demonstrated that when Medifocus's focused heat therapy alone was delivered prior to surgery, 0 of 34 (0%) of the tumors removed had positive margins whereas in the surgical arm without receiving the focused heat treatment, 4 of 41 or almost 10% had positive margins.

 

This study, along with the positive clinical efficacy results of another randomized study for the treatment of large breast cancer tumors that Medifocus reported last week, demonstrates that Medifocus's focused heat technology can potentially treat the majority of all localized and invasive breast cancer tumors detected. The study reported last week, demonstrated that when the Medifocus's focused heat was added to the standard of care (SOC) neo-adjuvant chemotherapy in the treatment of large breast cancer tumors, tumor shrinkage was increased by an additional 50% over that induced by (SOC) chemotherapy alone.

 

The treatment goal of the Medifocus study on early stage breast cancer, is to demonstrate that focused heat treatment delivered prior to surgery can improve surgical outcomes and decrease the need for re-excisions or a second incision which can improve cosmesis and may reduce recurrent rates of the breast cancer.

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Hovione's TwinCaps Inhaler in Phase III Clinical Trials for Influenza

Hovione is pleased to announce that its licensee Daiichi Sankyo (Tokyo, Japan) has informed that it intends to use Hovione's TwinCaps dry powder inhaler device in the launch of the compound CS-8958, an inhaled long-acting neuraminidase inhibitor active against the influenza virus. Daiichi Sankyo has completed patient enrolment for Phase III clinical trials in Japan and other Asian countries and results are expected to be released mid year, including data to confirm the device switching. TwinCaps was specifically developed by Hovione for the indication and licensed to Daiichi Sankyo and Biota Holdings Ltd (Victoria, Australia).

 

The announcement follows the recent publication of data indicating that the compound is as effective as Relenza and Tamiflu against various influenza strains. Significantly this efficacy is achieved with a single dose, as opposed to a treatment over five days for the established drugs.

 

A 20 mg dose of CS-8958 is inhaled from powder compartments in the TwinCaps inhaler, which is made of just two plastic parts. Hovione believes this is currently the simplest inhaler being tested in clinical trials and once approved, will be the simplest in the market and have the lowest cost of goods. TwinCaps has no moving parts to deaggregate the dose of powder and only requires a low inspiratory airflow to achieve optimal delivery to the lung. This means that children and the elderly will find it easier to inhale the full dose.

 

The design challenge for Hovione was to make TwinCaps extremely simple to use, as in the case of a pandemic requiring immediate treatment of large populations, there is an obvious advantage for simple operation. The TwinCaps DPI (to be manufactured in Japan and Europe) is a two-piece unit comprising body and shuttle components. The shuttle has two pre-filled dose chambers, left and right. In use, the shuttle is moved to one side by the patient to align one chamber of the shuttle with the mouth piece to allow the first inhalation, creating turbulence within the dose chamber and drawing the dry powder into the lung of the patient. The process is then repeated for the second dose chamber, as the shuttle is moved to the opposite side to permit another inhalation to take place. Visit http://www.hovione.com/twincaps.

 

Daiichi Sankyo has indicated that they are planning to file NDA in Japan in March 2010 and get approval within 2010, while Daiichi Sankyo and Biota are seeking licensees for the drug product collaboratively for the rest of world market. Hovione retains the right to commercialize TwinCaps outside the field of influenza.

 

 

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Infinity Pharma terminates late-stage trial in gastrointestinal stromal tumors

Infinity Pharmaceuticals, Inc., a cancer drug discovery and development company, announced the termination of a phase 3 registration trial of its lead cancer drug candidate IPI-504, or retaspimycin hydrochloride, due to safety concerns. The stock plummeted nearly 38% in morning trade.

 

A higher than anticipated death rate among patients enrolled in the trial was observed by the company's independent data monitoring committee when an early review of safety data from the first 46 patients enrolled in the study was conducted.

 

The RING trial, a double blind, placebo-controlled international Phase 3 registration trial of IPI-504 was carried out in patients with refractory gastrointestinal stromal tumors, or GIST, resistant to treatment.

 

The company intends to fully analyze the data from the trial in order to inform the ongoing development of IPI-504.

 

Julian Adams, president of research and development and chief scientific officer said that the outcome is disappointing, but the company is committed to the development of both IPI-504 and the oral Hsp90 inhibitor, IPI-493 in non-small cell lung cancer.

 

Looking forward, Infinity reiterated that it has capital to fund its current operating plan through at least the end of 2012. Infinity ended the first quarter of 2009 with approximately $153 million in cash, cash equivalents, and available-for-sale securities. Additionally, the company said that it has access to a $50 million line of credit from Purdue Pharma.

 

INFI is trading down $2.47 or 28.62% at $6.16 on a volume of about 376 thousand shares.

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Pfizer and Medivation Initiate Phase 3 Trial of Dimebon Added to Donepezil in Patients with Alzheimer's Disease

Pfizer and Medivation, Inc. announced the initiation of a 12-month, Phase 3 clinical trial of the investigational drug Dimebon. The study, known as CONCERT, is designed to evaluate the safety and efficacy of Dimebon when added to ongoing treatment with donepezil HCI tablets, the leading Alzheimer's disease (AD) medication worldwide, in patients with mild-to-moderate AD.

 

The CONCERT study is part of a broad, Phase 3 clinical development program for Dimebon. The study builds on data from a small-scale safety and tolerability trial of Dimebon added to donepezil, which found the combination to be well tolerated. CONCERT is designed to complement previous and ongoing studies by further evaluating the efficacy of Dimebon. The Phase 3 program also includes the confirmatory 6-month CONNECTION study, which is designed to evaluate the safety and efficacy of Dimebon monotherapy in patients with mild-to-moderate AD and builds on results of the first pivotal trial of Dimebon in AD.

 

Dimebon is an investigational compound currently in Phase 3 development for the treatment of Alzheimer's disease (AD) and in clinical development for Huntington's disease (HD). In preclinical models of AD and HD explored thus far, Dimebon has been shown to inhibit brain cell death, potentially by stabilizing and improving mitochondrial function in a way that prevents neuron death and dysfunction. The Dimebon mechanism is thought to be distinct from currently available AD medications.

 

Design of the CONCERT Study

The international, randomized, double-blind, placebo-controlled study will enroll approximately 1,050 patients with mild-to-moderate AD at approximately 100 sites in the United States, Australia, New Zealand and Western Europe. Patients on a stable dose of donepezil will be randomized to one of three treatment groups: Dimebon 20 mg three times per day, Dimebon 5 mg three times per day or placebo. Patients must be on treatment with donepezil for at least six months and at a stable dose of 10 mg daily for at least four months prior to enrollment in the study.

 

The primary endpoints are the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) and the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) - a measure of self-care and daily function.

 

For more information on the CONCERT study, please visit www.concertstudy.com or call 877-888-6386.

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Novagali Pharma Completed a New Phase II With Cyclokat in Dry Eye

Novagali Pharma, a French pharmaceutical ophthalmic company, announced successful completion of a new Phase II clinical study with Cyclokat, its formulation of Cyclosporine. The results demonstrate statistically significant improvement with signs and symptoms in patients suffering from moderate-to-severe dry eye syndrome.

 

For this dry eye clinical trial, Novagali worked with Ora, Inc., a leading global clinical research and development organization located in Andover, MA, USA. This phase II, multi-centre, randomized, double-masked, vehicle controlled study of 132 patients evaluated the safety and efficacy of Cyclokat(R) applied once-a-day over three months. Ora's proprietary Controlled Adverse Environment (CAE) clinical model was used in this study conducted in the US.

 

Efficacy was observed post-CAE as well as pre-CAE (environmental comparisons following selection and enrollment of patients utilizing the CAE). Cyclokat(R) demonstrated significant treatment effect on multiple efficacy variables for both signs and symptoms at Month 1 and Month 3. . These findings confirm potential clinical interest of Cyclokat(R) for the treatment of dry eye syndrome.

 

"We are very enthusiastic about the results of this new trial demonstrating efficacy on both dry eye signs and symptoms" said Jerome Martinez, CEO of Novagali "These are promising results which make us confident in the success of our ongoing Phase III which outcomes are expected 4Q2009″.

 

A pivotal Phase III trial is ongoing in Europe and patient recruitment has been already completed.

 

 

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Diamyd Discussing Potential Consolidation of Phase III Trials

Diamyd Medical is conducting two clinical Phase III trials of the Diamyd diabetes vaccine in children and adolescents with recent onset type 1 diabetes: one in the U.S. and one in nine European countries. In parallel, the company is discussing with the regulatory agencies about combining the two trials into one global trial.

 

In addition to reducing costs, combining the trials would mean that countries with the fastest rate of patient recruitment could contribute to the greatest extent. The Phase III program encompasses ten countries: Italy, Finland, France,the Netherlands, Slovenia, Spain, the UK, Sweden, Germany and the U.S. The plan is for the global trial to serve as the basis for market approval in both Europe and the U.S. Diamyd Medical's continued intention is to report Phase III data during the fourth quarter of 2010.

 

Patient recruitment is growing sharply at present, as more clinics are being added. There are currently 74 active recruiting clinics in the U.S. and Europe, 34 of which have joined since the beginning of the year.

 

"We estimate that the expanded number of clinics will enable us to screen 100 children and adolescents in April," says Elisabeth Lindner, President and CEO of Diamyd Medical.

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