Bristol-Myers Squibb Company / ZymoGenetics, Inc.

Hepatitis C Virus (HCV) Infection

$4.0B Global HCV market 2009 (~$8.5B projected by 2016)

Disease Overview

Hepatitis C is a chronic liver infection caused by HCV that can progress to cirrhosis, liver failure, and hepatocellular carcinoma. In 2010, ~3.5M Americans were living with chronic HCV; standard-of-care was pegylated interferon alfa plus ribavirin — a 24–48 week regimen with significant flu-like and hematologic toxicity and modest cure rates.

Competitive Landscape

When BMS agreed to buy ZymoGenetics in September 2010, the HCV race was pivoting from interferon-based regimens toward direct-acting antivirals (DAAs). Vertex's telaprevir (Incivek) and Merck's boceprevir (Victrelis) — first-generation NS3/4A protease inhibitors — were nearing 2011 approval with PEG-IFN/RBV backbones, lifting genotype-1 SVR from ~45% to ~70%. Earlier-stage rivals included Pharmasset's PSI-7977 (later sofosbuvir/Sovaldi, the eventual market disruptor) and Idenix's nucleotide programs. ZymoGenetics' PEG-Interferon lambda (BMS-914143) was a Type III interferon (IL-29) targeting a more restricted receptor distribution than IFN-alfa — the thesis was equivalent antiviral activity with materially fewer hematologic and flu-like side effects, an attractive backbone for emerging all-oral DAA combos. BMS already had the NS5A inhibitor daclatasvir and NS3 protease asunaprevir in development, so PEG-IFN lambda gave it a differentiated interferon component to anchor combinations. The thesis was rapidly overtaken by Gilead's 2013 launch of Sovaldi and the 2014 Harvoni all-oral, interferon-free regimen — IFN-lambda development was eventually wound down as the entire interferon class became obsolete.