Clinical Trials Report Final Results on New Treatments for Hepatitis C Virus

Gastroenterology
Volume 140, Issue 1 , Page 6, January 2011

Les Lang

published online 15 November 2010.

Richard Peek and K. Rajender Reddy, Section Editors

Results of clinical trials of 2 new treatments for hepatitis C (HCV) that enhance sustained viral response (SVR) rates were presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases in Boston, Massachusetts, October 29–November 2, 2010.

SVR have been <50% in HCV G1 patients, especially in black Americans. The SPRINT-2 study assessed the safety and efficacy of Boceprevir (BOC), a HCV-NS3 protease inhibitor, when combined with peginterferon alfa-2b/ribavirin (P/R) for treatment-naïve patients with HCV genotype (G) 1. This Phase III, international, double-blind, randomized study compared a 4-week lead-in (LI) treatment period with P/R, followed by (1) P/R plus placebo for 44 weeks (48P/R); (2) response-guided therapy (RGT): BOC plus P/R for 24 weeks, with an additional 20 weeks of P/R only if detectable HCV RNA during weeks 8–24 (LI+24 BOC/P/R*20 P/R); or (3) BOC plus P/R for 44 weeks (LI+44 BOC/P/R). The primary efficacy end point was SVR 24 weeks post-therapy in all randomized patients treated with any study medication. Non-black (cohort 1) and black (cohort 2) patients were enrolled and analyzed separately per protocol. Final results showed that BOC/P/R significantly increased SVR in both the RGT and 48-week treatment arms over standard of care by ∼70%. BOC was well tolerated; although reported more often in BOC recipients, anemia rarely led to treatment discontinuation. Compared with 44 weeks of triple therapy after the LI period, RGT with LI+24BOC/P/R*20P/R produced comparable SVR.

Also presented at American Association for the Study of Liver Diseases were final results of the Phase III ADVANCE Study, a 3-arm double-blind, randomized, placebo-controlled trial assessing efficacy and safety of 2 telaprevir (TVR, T)-based, response-guided regimens that were compared with peginterferon alfa-2a 180 μg per week and ribavirin 1000–1200 mg/d (PR) in treatment-naïve patients with chronic HCV G1 infection. The researchers report that a significantly greater proportion of patients achieved SVR with 12- and 8-week telaprevir-based combination regimens (75% and 69%, respectively). This was compared with the PR, 48 weeks control arm (44%; P < .0001). The safety and tolerability profile of telapervir in this trial was consistent with the profile previously reported. There also was improvement in treatment discontinuation rates owing to adverse events, including rash and anemia.

Another treatment trial called the ILLUMINATE study also evaluated telaprevir therapy along with pegylated interferon and ribavirin and demonstrated that the paradigm of RGT, as noted in the SPRINT-2 and ADVANCE studies as well, is very likely to become the standard of care as the treatment duration can be truncated in the majority of patients, while not compromising rates of SVR.

PII: S0016-5085(10)01635-5
doi:10.1053/j.gastro.2010.11.031
© 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

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