ZymoGenetics Reports Positive Interim Phase 1b Results In Hepatitis C

Main Category: Liver Disease / Hepatitis
Also Included In: Clinical Trials / Drug Trials
Article Date: 04 Nov 2008 - 8:00 PDT

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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.

Presentation

The AASLD presentation is available on the ZymoGenetics website at: http://www.zymogenetics.com.

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.

Hepatitis C

Chronic infection with HCV is a leading cause of cirrhosis, liver failure and hepatocellular carcinoma worldwide. The current standard of care for chronic HCV infection involves treatment with PEG-Interferon alpha and ribavirin. This form of HCV therapy has been associated with a number of significant side effects including flu-like symptoms, anorexia, depression, hemolytic anemia and myelosuppression. This side-effect profile often necessitates additional medications to manage the side effects and can lead to early discontinuation of treatment and poor adherence to prescribed therapy, leading to poor treatment outcomes. Currently, the response rates for the most common form of HCV in the United States to standard treatment are only 50%. Therefore, there remains a need for better tolerated and more effective therapy for HCV. The development of PEG-Interferon lambda is intended to provide an alternative to PEG-Interferon alpha.

About ZymoGenetics

ZymoGenetics discovers and develops novel protein therapeutics that are based on the company's research and biological insights into key disease pathways. The Company developed and markets RECOTHROM® Thrombin, topical (Recombinant). Other product candidates span a wide array of clinical opportunities that include cancer, autoimmune and viral diseases. ZymoGenetics intends to commercialize product candidates through internal development, collaborations with partners, and out-licensing of patents from its extensive patent portfolio. For further information, visit http://www.zymogenetics.com.

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on the current intent and expectations of the management of ZymoGenetics. These statements are not guarantees of future performance and involve risks and uncertainties that are difficult to predict. ZymoGenetics' actual results and the timing and outcome of events may differ materially from those expressed in or implied by the forward-looking statements because of risks associated with our unproven product sales and marketing abilities, discovery strategy, preclinical and clinical development, strategic partnering, regulatory oversight, intellectual property claims and litigation and other risks detailed in the company's public filings with the Securities and Exchange Commission, including the company's Annual Report on Form 10-K for the year ended December 31, 2007. Except as required by law, ZymoGenetics undertakes no obligation to update any forward-looking or other statements in this press release, whether as a result of new information, future events or otherwise.

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