Response-guided Telaprevir Combination Treatment in Genotype 1 Chronic Hepatitis C Patients who had Prior Relapse to Peginterferon Alfa-2a/Ribavirin

Abstract

Purpose: Results of the Phase 2 (PROVE3 and Study 107) and Phase 3 (ADVANCE, ILLUMINATE, and REALIZE) telaprevir (T) studies have indicated that patients who relapsed to a prior peginterferon /ribavirin (PR) therapy had high on-treatment response and sustained virologic response (SVR) rates, comparable to the SVR rates in treatment-naïve patients. Methods: A post-hoc analysis of SVR and relapse rates was performed in patients with prior relapse according to treatment duration and undetectable HCV RNA at weeks 4 and 12 (eRVR), and compared with treatment-naïve patients. Additionally, a viral dynamic model was developed to predict SVR rates by different PR treatment durations in both treatment-naïve and prior relapse patients. Results: Baseline characteristics and demographics in prior relapsers who had eRVR were similar to treatment-naïve patients. In addition, early viral responses at weeks 4 and 12 were similar between T12PR48 in prior relapsers and T12PR24 in treatment-naïve patients. Relapse rates in treatment-naïve patients with eRVR were 6% (T12PR24) and 1% (T12PR48) in ILLUMINATE. In prior relapsers, the overall relapse rate was 3% in REALIZE. In prior relapsers with eRVR, the relapse rate was 7% (2/28) and 0% (0/24) in T12PR24 patients in PROVE3 and Study 107, respectively. The model predicted that the differences in SVR rates between T12PR regimens with and without responseguided PR duration in both treatment-naïve and in prior relapsers were similar (1-2%), consistent with observed clinical data. Conclusion: Among prior relapse patients who had eRVR and were treated with 24-week telaprevir combination treatment, SVR rates were comparable to or higher than those in treatment-naïve patients, and relapse rates were low. Modeling predictions and the observed clinical data support the use of response-guided therapy in prior relapse patients. Disclosure: Drs. Adiwijaya, Gritz, Bengtsson, Kauffman and Adda are employees and stock holders of Vertex Pharmaceuticals Incorporated Dr. Luo is an employee and stock holder of Tibotec BVBA Dr. Poordad has received lecture fees from Genentech, Gilead, Salix Pharmaceuticals and Grant/Research Support from Bristol-Meyers Squibb, Gilead, Human Genome Services, GlaxoSmithKline, Idenix Pharmaceuticals, Intarcia Therapeutics, Merck, Novartis, Roche, Schering-Plough, Vertex Pharmaceuticals and has served on Advisory Committees or Review Panels for Abbott, Genentech, Pfizer and Vertex Pharmaceuticals Dr. Muir has received consulting/lecture fees from Merck & Co., Vertex Pharmaceu-ticals and Zymogenetics and Grant/Research support from Anadys, Genentech, Idera, Medtronic, Merck & Co., Pharmasset, Santarus, Three Rivers Pharmaceuticals, Scynexis, Vertex Pharmaceuticals and ZymoGenetics.Table: SVR rates in patients with eRVR