CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

576

Safety and Tolerability of Elbasvir/Grazoprevir in Chronic Hepatitis C Infection Mark S. Sulkowski 1 ; Geoffrey M. Dusheiko 2 ; Michael Manns 3 ; John M.Vierling 4 ; Rajender Reddy 5 ; Paul Kwo 6 ; Eric Lawitz 7 ; JaniceWahl 8 ; Barbara Haber 8 1 Johns Hopkins Univ, Baltimore, MD, USA; 2 Royal Free Hosp Univ Coll London, London, UK; 3 Medizinische Hochschule Hannover, Hannover, Germany; 4 Baylor Coll of Med, Houston, TX, USA; 5 Hosp of the Univ of Pennsylvania, Philadelphia, PA, USA; 6 Indiana Univ Sch of Med, Indianapolis, IN, USA; 7 Texas Liver Inst, San Antonio, TX, USA; 8 Merck & Co, Inc, Kenilworth, NJ, USA Background: In phase 2-3 studies, treatment with elbasvir (EBR) 50 mg/grazoprevir (GZR) 100 mg ± ribavirin (RBV) resulted in high rates of sustained virologic response (SVR) in hepatitis C virus (HCV)-infected patients, including those with compensated cirrhosis. The purpose of this analysis was to define the overall safety profile of EBR/GZR given for 8, 12, 16, or 18 weeks in these studies. Methods: Clinical adverse events (AEs) and laboratory abnormalities reported on therapy, or within 14 days of end of treatment, were compared in 1795 patients, of whom 1033 received EBR/GZR without RBV, 657 received EBR/GZR with RBV, and 105 received placebo. Results: A diverse population was enrolled: 61%were male and 13%were black/African American; mean age was 52.6 years (11%≥65 years); 27% had compensated cirrhosis; and 18%were HIV/HCV coinfected. The overall safety profiles of EBR/GZR (without RBV) and placebo were comparable (Table). The addition of RBV was associated with more AEs. Among patients who received EBR/GZR, there were 3 deaths (ventricular arrhythmia, strangulated hernia, motor vehicle accident); all 3 were unrelated to study medication. No patients who received placebo died. The frequency of adverse events was not associated with sex, age, presence of cirrhosis, or HIV/HCV coinfection. Late serum alanine aminotransferase (ALT) elevations (defined as >5× upper limit of normal, in patients who had normal ALT values between treatment week [TW] 2-4) were noted in 0.8 % of patients, generally at/after TW8 . These were typically asymptomatic, resolving with continued therapy, scheduled end of therapy, or (in 3/1690, 0.18%) a protocol-mandated stop of therapy, and they were not associated with hyperbilirubinemia. Conclusions: EBR/GZR ± RBV was generally well tolerated in a large, diverse patient population with a low serious AE rate. Fewer discontinuations due to AEs and overall improved tolerability with lower reductions in hemoglobin and lower elevations in total bilirubin were demonstrated in the RBV-free cohort. ALT elevations occurring late in the course of therapy were infrequent and not clinically significant.

Poster Abstracts

229

CROI 2016