Bristol-Myers Squibb, ZymoGenetics Release Final Phase 1b Results For PEG-Interferon Lambda

Bristol-Myers Squibb and ZymoGenetics have released final results from phase 1b clinical trial of PEG-Interferon lambda administered with ribavirin in relapsed and treatment-naive hepatitis C virus (HCV) patients.

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.

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-naïve patients.

In the single agent arm of the study with treatment-relapsed patients, PEG-Interferon lambda was administered subcutaneously at 1.5mcg/kg and 3mcg/kg weekly for four weeks, and 1.5 mcg/kg and 3 mcg/kg every two weeks.

However, in the combination arm of the study with treatment-relapsed patients, PEG-Interferon lambda was administered subcutaneously weekly at 0.5mcg/kg, 0.75mcg/kg, 1.5mcg/kg and 2.25mcg/kg for four weeks, with daily oral ribavirin administered consistent with the package insert. Patients in the cohort of treatment-naïve patients were given 1.5mcg/kg of PEG-Interferon lambda and ribavirin.

PEG-Interferon lambda demonstrated antiviral activity at all dose levels tested in both relapse and treatment naïve HCV patients. A majority of patients across all treatment arms achieved a greater than 2 log reduction in HCV RNA.

In the study, of the patients in the single agent arm of the study, all 12 of those patients receiving 1.5mcg/kg and 3mcg/kg weekly for four weeks achieved a greater than 2 log decrease in HCV RNA. Five of the 12 patients receiving 1.5mcg/kg and 3mcg/kg every two weeks for four weeks achieved a greater than 2 log decrease in HCV RNA.

At PEG-Interferon lambda doses of 0.75mcg/kg, 1.5mcg/kg and 2.25mcg/kg administered in combination with ribavirin in treatment-relapsed patients, a greater than 3 log mean maximum decrease in viral load was observed. Of those patients, 61% had less than 1,000 HCV RNA copies at Day 29.

Moreover, in the treatment-naive patients, who were treated with 1.5mcg/kg of PEG-Interferon lambda in combination with ribavirin, also had a greater than 3 log mean maximum decrease in viral load and 29% achieved a rapid virologic response (RVR), or undetectable HCV RNA copies, at 4 weeks.

Overall, the results of the study support moving to dose-ranging phase 2 studies in treatment-naive HCV patients.

Eleanor Ramos, senior vice president and chief medical officer of ZymoGenetics, said: “We are excited about the prospects for PEG-Interferon lambda as a potential HCV treatment. 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.”