On an intent-to-treat basis (subjects who received at least one dose of combination therapy), prior non-responders receiving GI-5005 plus standard of care (SOC, pegylated-interferon alpha 2a plus ribavirin) as a triple therapy had a sustained virologic response rate of 17%, compared to an SVR rate of only 5% in patients receiving SOC alone. Prior non-responders in this study were defined as patients who did not clear virus after a minimum of 12 weeks of SOC, including null responders, poor responders, and partial responders. Relapsers and on-treatment breakthroughs were not enrolled in the study. The most common adverse events associated with GI-5005 were injection site reactions that were generally mild and transient in nature. Discontinuation rates due to adverse events in the GI-5005 triple therapy arm were comparable to the discontinuation rates in the SOC alone arm.
"Only 4-7% of patients with genotype 1 HCV who were null, poor or partial responders to their first course of pegylated interferon-based therapy would be expected to achieve a sustained virologic response with a second course of treatment," said Dr. Pockros. "In this study, GI-5005 conferred a three-fold improvement in SVR, an important treatment effect in this challenging patient population."
Additional immunology data from the study will be presented in a poster on Tuesday, November 2, 2010 by John M. Vierling, M.D., of Baylor College of Medicine. These data show that GI-5005 improved HCV-specific T cell responses 10-fold over SOC alone in patients with the IL28B T/T genotype (~20% of chronically infected patients), the subgroup most likely to fail treatment with SOC alone. Patients with the IL28B T/T genotype receiving SOC alone had an HCV-specific cellular immune response that was 17-fold lower than patients in the IL28B C/C or C/T subgroups. The improved HCV-specific T cell immunity in IL28B T/T patients receiving GI-5005 plus SOC correlates with previously reported data that demonstrated GI-5005 increased SVR rates by 60% in interferon-naïve T/T patients compared to T/T patients receiving SOC alone.
"These data suggest that the fundamental deficit in patients carrying the T allele of the IL28B gene is a deficit in adaptive cellular immunity, the mechanism that GI-5005 was designed to address," said David Apelian, M.D., Ph.D., Chief Medical Officer at GlobeImmune. "We are confident that GI-5005 will become a cornerstone of HCV therapy, particularly for difficult to treat populations, such as IL28B T/T patients."
A 40 patient expansion of this study in patients having the IL28B T/T genotype was initiated last week to further explore the potential treatment effect of GI-5005 in this patient population.
GI-5005 is a therapeutic vaccine candidate designed to generate HCV-specific T-cell responses and improve virologic responses in patients with chronic hepatitis C virus infection.