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Peginterferon Lambda-1a, a New Therapeutic for Hepatitis C Infection, from Bench to Clinic

Journal of Clinical and Translational Hepatology 2013年第2期1卷 116-124页

作者： Henrik Andersen Jeff Meyer Jeremy Freeman Sean E.Doyle Kevin Klucher Dennis M.Miller Diana Hausman Jan L.Hillson ZymoGenetics/Bristol-Myers Squibb Seattle WA 98102 USA EMD Serono Billerica MA USA Oncothyreon Inc. Seattle WA USA cptxbio Woodinville WA USA

Chronic infection with hepatitis C virus (HCV) is estimated to affect approximately 3% of the world's population and cause 350,000 deaths each *** number of years,the standard of care has been combination therapy with recombinant alfa interferons—originally as native proteins but more recently as polyethyleneglycol-modified derivatives—and ribavirin,with the recent addition of an NS3 protease inhibitor for HCV genotype ***,therapeutic alfa interferons are associated with a significant burden of treatment-limiting adverse events,including musculoskeletal and influenza-like symptoms,hematologic cytopenias,autoimmune disease,fatigue,and other neurologic *** 2003,a team at ZymoGenetics (now a fully owned subsidiary of Bristol-Myers Squibb) and a second,independent group simultaneously identified a new class of interferons—the type Ⅲ lambda interferons—with near-identical activity to the type Ⅰ alfa interferons in hepatocytes but with an unrelated and less ubiquitous *** evaluation of the type Ⅲ interferon system demonstrated antiviral activity against HCV in vitro with limited activity in peripheral blood mononuclear cells and other nonhepatocyte cell types,supporting its development as a potentially better-tolerated therapy for viral *** lambda-1a (Lambda) is an investigational type Ⅲ therapeutic agent originally developed at ZymoGenetics that is currently in Phase 3 studies for the treatment of *** this review,we describe the selection of the Lambda molecule and its preclinical and early clinical development,and how the resulting data have helped to establish the differentiated safety profile for Lambda—with fewer influenza-like and musculoskeletal symptoms and less hematologic toxicity than the alfa interferons—that was seen in later studies.

关键词： Discovery HCV Interferonλ

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