Small 1b trial, but given that caveat . . . very good data for PEG-interferon lambda.
>>PRINCETON, N.J. & SEATTLE--(BUSINESS WIRE)--Bristol-Myers Squibb (NYSE:BMY - News) and ZymoGenetics, Inc. (NASDAQ:ZGEN - News), today reported that the administration of the investigational compound PEG-Interferon lambda in combination with ribavirin in 10 patients resulted in a significant reduction in hepatitis C virus (HCV) RNA and was well tolerated in patients with relapsed HCV in an ongoing Phase 1b clinical trial. Antiviral activity was observed at all dose levels tested either as single agent or in combination with ribavirin. Treatment was well-tolerated with reversible, dose-dependent increases in liver enzyme levels and bilirubin. There was no evidence for potentiation of ribavirin-induced toxicities in the combination groups. The interim results were presented at the European Association for the Study of the Liver (EASL) annual meeting in Copenhagen, Denmark.
“PEG-Interferon lambda showed antiviral effects as a single agent and also in combination with ribavirin. The lack of hematologic adverse effects in the trial is very encouraging,” said Mitchell Shiffman, M.D., Virginia Commonwealth Medical Center.
The Phase 1b clinical trial was designed to evaluate the safety and antiviral activity of PEG-Interferon lambda as a single agent or in combination with ribavirin in genotype 1 HCV patients with relapsed disease. The single agent part of the study, designed to assess PEG-Interferon lambda administered subcutaneously either with a weekly or every other week dose-escalation schedule at 1.5 mcg/kg and 3.0 mcg/kg for four weeks, is complete. In the combination part of the study, data are available for the first 10 subjects who have received weekly subcutaneous administration of PEG-Interferon lambda at doses of 0.75 mcg/kg (3 patients) or 1.5 mcg/kg (7 patients) with daily oral ribavirin administered per the package insert over a four-week period.
Antiviral activity was seen in all cohorts, with a mean maximum decrease in HCV RNA viral load of at least 3.0 log10 in all single agent and combination cohorts receiving weekly dosing. Of the 22 patients dosed weekly, 86% showed a 2 log10 or greater decrease in HCV RNA at Day 29 and 50% had less than 1,000 HCV RNA copies. Of the six patients treated weekly with 3.0 mcg/kg single agent, 50% achieved a rapid virologic response (RVR; undetectable HCV RNA copies at 4 weeks).
PEG-Interferon lambda was well tolerated over four weeks of treatment with minimal hematologic effects or constitutional symptoms. No fever was reported. The majority of adverse events were Grade 1 or 2, the most common of which were fatigue (18%) and nausea (18%). Reversible, dose-dependent increases in liver enzymes (ALT, AST) meeting the protocol criteria for dose-limiting toxicity were observed in four patients, of which three also experienced reversible increases in bilirubin. There were no clinically significant changes in serum chemistry or renal function. Decreases in mean hemoglobin values occurred only in ribavirin cohorts, and there was no neutropenia.
Presentations
Two poster presentations will be given at the EASL 2009 Annual Meeting:
Friday, April 24, 2009
Time: 02:00 a.m. – 12:00 p.m. EDT
Poster Board #: 643
Title: PEG-IFN-?: Antiviral Activity And Safety Profile In A 4-Week Phase 1B
Study In Relapsed Genotype 1 Hepatitis C Infection
Session Title: Category 5G: Viral Hepatitis – g Hepatitis C – Clinical (Therapy)
Saturday, April 25, 2009
Time: 02:00 a.m. – 12:00 p.m. EDT
Poster Board #: 942
Title: Viral Kinetic Modeling During Treatment With Interferon Lambda-1A In
Genotype 1 Chronic Hepatitis C Patients
Session Title: Category 5H: Viral Hepatitis – h Hepatitis C – Clinical (New
Compounds, Resistance)
The EASL poster presentations will be made available on the ZymoGenetics website at www.zymogenetics.com.
PEG-Interferon lambda
PEG-Interferon lambda (IL-29) is a novel type 3 interferon currently in Phase 1b development for hepatitis C. The native human protein Interferon lambda is generated by the immune system in response to viral infection.
About Hepatitis C1
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with blood. An estimated 170 million people worldwide are infected with hepatitis C and, of these, 94.5 million people live in the Asia Pacific region. One to five percent of people with chronic infection will develop liver cancer. Although there is no vaccine to prevent hepatitis C, it is a curable disease.<<
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Cheers, Tuck |
