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Peg-Interferon Lambda Phase 1b in HCV+ Patients: safety, antiviral activity
  See Phase 1b in patients slides below following press release
The companies BMS & ZymoGenetics have agreed to co-develop PEG-interferon lambda in the USA and Europe, with ZymoGenetics retaining rights to co-market the drug in the former territory and share profits. Should the Seattle-based group opt out of the co-promotion agreement, the company would receive double-digit royalties on global product sales.
Francis Cuss, senior vice president of discovery and exploratory clinical research at B-MS, said that the profile of PEG-interferon lambda "offers the possibility of improvements in the safety and effectiveness of combination treatment for hepatitis C and makes it an ideal fit with our emerging portfolio of small molecule anti-virals".
The firms said that PEG-interferon lambda has the potential to be "uniquely differentiated from available interferon therapy" because it mediates anti-viral activity through a receptor that is distinct from that used by interferon alpha and is present on fewer cell types within the tissues of the body. As a result, "the possibility exists for more targeted delivery of interferon therapy and an improved therapeutic index,", they added.
ZymoGenetics Presents Positive Interim Phase 1b Results in Hepatitis C
- Significant Viral Load Reduction and Encouraging Tolerability With PEG-Interferon lambda -
SEATTLE--(BUSINESS WIRE)--Nov. 3, 2008--ZymoGenetics, Inc. (NASDAQ:ZGEN) today reported that PEG-Interferon lambda showed a meaningful reduction in the amount of Hepatitis C Virus (HCV) and was well tolerated in patients with relapsed HCV in an ongoing Phase 1b clinical trial. Anti-viral activity was observed at all dose levels tested. The six patients treated once a week with 1.5 mcg/kg of PEG-Interferon lambda had a mean maximum decrease of 3.6 logs in viral load at Day 29. Treatment had minimal side effects and no hematologic toxicity. Results from 18 patients, or 3 cohorts with 6 patients each, were presented at the American Association for the Study of Liver Diseases (AASLD) annual meeting.
"PEG-Interferon lambda has become one of our company's key assets," said Nicole Onetto, M.D., Senior Vice President and Chief Medical Officer of ZymoGenetics. "Based on these early results, we're encouraged by the potential for PEG-Interferon lambda to become an effective treatment with improved tolerability for treating patients with Hepatitis C. We've accelerated the timeline for the second part of the study, where the combination of PEG-Interferon lambda and ribavirin will be investigated."
The Phase 1b clinical trial is evaluating the safety and anti-viral activity of PEG-Interferon lambda in genotype 1 HCV patients with relapsed disease. To date, in the single agent part of the study, PEG-Interferon lambda has been administered subcutaneously either with a weekly or biweekly schedule at doses of 1.5 mcg/kg or 3.0 mcg/kg for four weeks.
Anti-viral activity was seen in all cohorts, with the best anti-viral effect documented at 1.5 mcg/kg given weekly. All 6 patients treated in this cohort showed a 2 log or greater decrease in viral load at Day 29, with 4 of these patients having less than 1,000 HCV RNA copies at the end of treatment.
PEG-Interferon lambda was well tolerated at all dose levels, with no discontinuations due to toxicity, no treatment-related fever, no signs of hematological toxicity and no meaningful changes in hematological parameters. Adverse events were all Grade 1 or 2. Most common adverse events were fatigue and myalgia, which were observed in only 3 patients. Primary safety findings consist of asymptomatic, reversible and mild increases in liver enzymes in some patients.
PEG-Interferon lambda
The native human protein Interferon lambda is generated by the immune system in response to viral infection. Interferon lambda mediates anti-viral activity through a receptor that is distinct from that used by Interferon alpha and is present on fewer cell types within the tissues of the body. Receptors for Interferon lambda are present on several important sites of viral infection, most notably cells of the lung and liver. Recombinant PEG-Interferon lambda, a novel, pegylated Type III interferon, has shown in vitro anti-viral activity against several viruses, including HCV. A Phase 1a healthy volunteer, single dose study showed dose-dependent pharmacokinetics, evidence of biological activity (starting at 1.5 mcg/kg) and that PEG-Interferon lambda was well tolerated at pharmacologically active doses with no fever, flu-like symptoms or hematological effects. ZymoGenetics holds worldwide rights to PEG-Interferon lambda.
SOURCE: ZymoGenetics, Inc.
ZymoGenetics Presents PEG-Interferon Lambda Phase 1a Data 12/11/2007
Program to Advance to Phase 1b Study in Patients with Chronic Hepatitis C

SEATTLE, Dec 11, 2007 (BUSINESS WIRE) -- ZymoGenetics, Inc. (NASDAQ:ZGEN), today presented data from a Phase 1a clinical trial with PEG-Interferon lambda (also known as IL-29) in healthy volunteers showing that administration of single doses of PEG-Interferon lambda was well tolerated at doses that produced anticipated pharmacologic activity, including up-regulation of interferon response markers associated with antiviral effects. No fever or hematologic effects, which are typically seen with interferon alpha, were observed at any of the dose levels tested.
"Results from this single dose Phase 1a study in healthy volunteers support moving forward into a repeat dose Phase 1b study in patients with hepatitis C," said Nicole Onetto, M.D., Senior Vice President and Chief Medical Officer. "The biologically active dose levels observed in the Phase 1a study have been used to design a Phase 1b study to evaluate the safety and antiviral effects of repeat dosing in patients with relapsed hepatitis C infection. "We're hopeful this study will confirm preclinical findings indicating PEG-Interferon lambda has antiviral activity with greater tolerability for patients."
About the Phase 1a Study
The primary objectives of this randomized, placebo-controlled, dose-escalation Phase 1a study were to characterize the safety, tolerability and pharmacokinetics of a single dose of PEG-Interferon lambda administered subcutaneously. Twenty subjects were treated with PEG-Interferon lambda at dose levels up to 7.5 mcg/kg (n=17) or placebo (n=3). Administration of a single dose of PEG-Interferon lambda was associated with dose-related pharmacokinetic and pharmacodynamic effects and was well tolerated at biologically active doses. Evidence of biological activity, including up-regulation of interferon response markers, was seen starting at doses of 1.5 mcg/kg. These results suggest that antiviral activity against hepatitis C virus (HCV) might also be seen at these dose levels.
Overall, administration of PEG-Interferon lambda was well tolerated at doses up to 5 mcg/kg. No fever or hematologic effects were observed at any of the dose levels tested. The primary safety observations consisted of dose-related increases in liver transaminases without associated increases in bilirubin in a subset of patients treated at doses of 5 mcg/kg and higher, and minor decreases in fibrinogen not associated with bleeding or changes in platelet counts, all of which were reversible.
Results of the Phase 1a study with PEG-Interferon lambda were presented at the HEP DART 2007 meeting.











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