Telaprevir for Hepatitis C Virus Infection
Telaprevir for Hepatitis C Virus Infection
Abstract and Commentary
By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University, School of Medicine, is Associate Editor for Infectious Disease Alert.
Dr. Winslow serves as a consultant for Siemens Diagnostics, and is on the speaker's bureau for Boehringer-Ingelheim and GSK.
Synopsis: The Hepatitis C Virus (HCV) protease inhibitor telaprevir (TPV), when combined with pegylated interferon (pIFN) plus ribavirin (RBV), significantly improved sustained virologic response rates in patients infected HCV genotype 1.
Sources: McHutchison JG, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype infection. N Engl J Med. 2009;360:1827-1838; Hezode C, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection
In the first study, patients with Hepatitis C Virus (HCV) genotype 1 infection were randomized to one of four treatment groups: pegylated interferon (pIFN) + ribavirin (RBV) given for 48 weeks + TPV placebo given for 12 weeks (PR48) or pIFN+RBV given for 12 weeks + telaprevir (TPV) given for 12 weeks (T12PR12) or pIFN+RBV for 24 weeks + TPV 12 weeks (T12P24) or pIFN + RBV for 48 weeks + TPV 12 weeks (T12P48). Sustained virologic responses were seen in 41% (31/75) in the PR48 group, 61% (48/79) in the T12PR24 group, 67% (53/79) in the T12PR48 group, and 35% (6/17) in the T12PR12 group. In this study, 21% of patients in the TPV groups discontinued therapy (mainly due to rash) vs. 11% in the PR48 group.
In the second study, patients with HCV genotype 1 were randomized to PR48, T12PR24, T12PR12, and a T12P12 group (note that the last group of patients did not receive RBV). In this study, 46% (38/82) of the patients in the PR48 groups experienced SVR, 60% (49/82) in the T12PR12 group, 36% (28/78) in the T12P12 group, and 69% (56/81) in the T12PR24 group. Adverse events of pruritus, rash, and anemia were seen more frequently in the TPV groups than in the control group.
Commentary
Treatment of chronic HCV genotype 1 infections is very unsatisfactory with the current medications available (interferon plus ribavirin). While the use of pegylated formulations of IFN and weight-adjusted doses of RBV coupled with aggressive use of erythropoietin and G-CSF has modestly improved the rates of SVR, this infection requires 48 weeks of treatment, is still associated with significant adverse effects that impair quality of life, and has low associated response rates. HCV is a flavivirus that possesses a serine protease encoded by the nonstructural 3/4A region of the viral genome. Several companies have been actively identifying small molecule inhibitors of this protease.
Telaprevir is a small molecule serine protease inhibitor developed by Vertex Pharmaceuticals. The above two clinical studies clearly validate the NS3/4A serine protease as an appropriate target for HCV therapy and demonstrate improved SVR rates in HCV genotype 1 infected patients. While adverse effects (mainly skin rash) were seen more commonly in the TPV-treated patients than in the control patients, it is clear that TPV is an active agent. The infectious disease community eagerly awaits additional studies of TPV and the results of clinical trials with other small molecule HCV inhibitors currently in development.
In the first study, patients with Hepatitis C Virus (HCV) genotype 1 infection were randomized to one of four treatment groups: pegylated interferon (pIFN) + ribavirin (RBV) given for 48 weeks + TPV placebo given for 12 weeks (PR48) or pIFN+RBV given for 12 weeks + telaprevir (TPV) given for 12 weeks (T12PR12) or pIFN+RBV for 24 weeks + TPV 12 weeks (T12P24) or pIFN + RBV for 48 weeks + TPV 12 weeks (T12P48).Subscribe Now for Access
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