Pegylated Interferon Lambda Demonstrates Good Antiviral Activity, May Cause Fewer Side Effects than Interferon Alfa
Bristol-Myers Squibb and ZymoGenetics Present
Final Phase 1b Results for PEG-Interferon Lambda in Hepatitis C
Antiviral activity seen at all dose levels tested Results support moving to dose-ranging Phase II studies in treatment-naive HCV patients
Princeton, NJ and Seattle, WA -- October 31, 2009 -- Bristol-Myers Squibb Company (NYSE: BMY) and ZymoGenetics, Inc. (NASDAQ: ZGEN) today presented final results from a Phase 1b clinical trial of PEG-Interferon lambda administered with ribavirin in relapsed and treatment-naive hepatitis C virus (HCV) patients.
The poster included data on 56 patients in the study. Antiviral activity was observed at all dose levels tested. The results will be presented at the American Association for the Study of the Liver Diseases annual meeting in Boston on November 3. Interim results were previously presented at the European Association for the Study of the Liver annual meeting in April 2009.
"There is a strong need for additional options for hepatitis C patients," said Brian Daniels, MD, senior vice president, Global Development & Medical Affairs, Bristol-Myers Squibb. "We are pursuing this investigational pathway to address the fact that although current interferons have been the backbone of therapy with meaningful efficacy, they are often poorly tolerated, leading to dose reductions, poor compliance and avoidance of treatment."
"We are excited about the prospects for PEG-Interferon lambda as a potential HCV treatment," said Eleanor L. Ramos, MD, senior vice president and chief medical officer of ZymoGenetics. "There is a clear unmet medical need for an interferon with improved safety and tolerability. We look forward to obtaining additional clinical data on this promising investigational medicine."
The Phase 1b clinical trial was designed to evaluate the safety and antiviral activity of PEG-Interferon lambda when given as a single agent or in combination with ribavirin in genotype 1 HCV patients with relapsed disease and in treatment-naive patients.
In the single agent arm of the study with treatment-relapsed patients (n=24), PEG-Interferon lambda was administered subcutaneously at 1.5 mcg/kg and 3.00 mcg/kg weekly for four weeks, and 1.5 mcg/kg and 3.00 mcg/kg every two weeks. In the combination arm of the study with treatment-relapsed patients (n=24), PEG-Interferon lambda was administered subcutaneously weekly at 0.5 mcg/kg, 0.75 mcg/kg, 1.5 mcg/kg and 2.25 mcg/kg for four weeks, with daily oral ribavirin administered consistent with the package insert. Patients in the cohort of treatment-naive patients (n=7) were given 1.5 mcg/kg of PEG-Interferon lambda and ribavirin.
PEG-Interferon lambda demonstrated antiviral activity at all dose levels tested in both relapse and treatment naive HCV patients. A majority of patients across all treatment arms achieved a greater than 2 log reduction in HCV RNA.
Of the patients in the single agent arm of the study, all 12 of those patients receiving 1.5 mcg/kg and 3.0 mcg/kg weekly for four weeks achieved a greater than 2 log decrease in HCV RNA. Five of the 12 patients receiving 1.5 mcg/kg and 3.00 mcg/kg every two weeks for four weeks achieved a greater than 2 log decrease in HCV RNA.
At PEG-Interferon lambda doses of 0.75 mcg/kg, 1.5 mcg/kg and 2.25 mcg/kg administered in combination with ribavirin in treatment-relapsed patients (n=18), a greater than 3 log mean maximum decrease in viral load was observed. Of those patients, eleven (61%) had less than 1,000 HCV RNA copies at Day 29.
Treatment-naive patients, who were treated with 1.5 mcg/kg of PEG-Interferon lambda in combination with ribavirin (n=7), also had a greater than 3 log mean maximum decrease in viral load and two patients (29%) achieved a rapid virologic response (RVR), or undetectable HCV RNA copies, at 4 weeks.
The most common adverse events were fatigue (29%) and nausea (13%). There were minimal effects on neutrophil counts. Minimal constitutional symptoms or hematologic effects were observed with PEG-Interferon lambda given as a single agent or in combination with ribavirin. The majority of adverse events and laboratory changes were grade 1 or 2. Dose-limiting elevations in ALT or AST, with or without an increase in bilirubin, were dose-dependent and reversible.
Overall, the results of the study support moving to dose-ranging Phase 2 studies in treatment-naive HCV patients.
About Interferon lambda
Interferon lambda (IL-29) is a type 3 interferon that binds to a unique receptor with more restricted distribution than the receptors targeted by type 1 interferons, such as interferon alpha. It is in development for hepatitis C. The native human protein Interferon lambda is generated by the immune system in response to viral infection. IL-29 is a member of the type 3 Interferon family, which includes IL-28A and IL-28B, and signals through the same receptor as IL-28A and IL-28B.
A Muir. ML Shiffman, A Zaman, and other. A Phase 1b Dose-Ranging Study of 4 Weeks of PEG-Interferon (IFN) Lambda (PEG-rIL-29) in Combination with Ribavirin (RBV) in Patients with Chronic Genotype 1 Hepatitis C Virus (HCV) Infection. 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston . October 30-November 1, 2009. Abstract 1591.