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Nelson DR, et al. Hepatitis C infection is the leading cause of end stage liver disease worldwide. Standard therapy with pegylated interferon and ribavirin have resulted in suboptimal responses, particularly for genotype 1. However, the advent of new direct-acting antiviral agents against HCV have resulted in dramatically improved rates of cure of the virus. In this issue, Nelson DR, et al., report the results of a randomized double-blinded, multi-center phase IIb clinical trial studying the efficacy, optimal treatment regimen, and safety of balapiravir, a nucleoside analogue inhibitor of HCV RNA dependent RNA polymerase. This study evaluated 516 treatment naive, chronic HCV mono-infected patients. All patients had HCV genotype 1 and were between the ages of 18-65 years. Patients were randomized to one of seven treatment groups in which they received different dosing combinations of balapiravir, pegylated interferon and ribavirin. HCV RNA counts were followed to assess for early and sustained virological suppression. While all patients demonstrated dose dependent reductions in serum HCV RNA levels, the study protocol was amended early, with discontinuation of the balapiravir arm with the highest dose and a reduction in duration from a planned 24 week to 12 weeks of balapiravir exposure in the other arms. This was due to the high incidence of serious adverse events attributed to balapiravir, including significant lymphopenia (< 0.5 x 10⁹), ocular adverse events, infections, and death in three patients attributed to study drug (varicella infection, lymphoma and suicide). The severe lymphopenia recovered in “most” of the patients although recovery was slow, taking up to one year post-treatment in some cases. The protocol dose amendments resulted in a relatively low sustained virologic response (SVR) of 29-50% compared to 43% for the peginterferon and ribavirin control arm. The significant toxicity especially the lymphopenia was surprising as it had not been reported in previous clinical trials. The adverse effect profile of the clinical trial resulted in the manufacturer (Hoffman La Roche) curtailing further drug development with balapiravir.

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2011-11-28   |   622 visitas   |   Evalua este artículo 0 valoraciones

Vol. 11 Núm.1. Enero-Febrero 2012 Pags. 4-6 Ann Hepatol 2012; 11(1)