Sofosbuvir-velpatasvir for 12 weeks is safe and effective in patients undergoing dialysis.

Abstract

Background and Aim: Approved hepatitis C virus (HCV) treatments for patients on dialysis are associated with complexities, including drug-drug interactions, baseline resistance testing, use of ribavirin, and risk of hepatotoxicity. Despite higher concentrations of the primary circulating sofosbuvir (SOF) metabolite, GS-331007, in severe renal impairment, real-world case series showed substantial use of SOF-based regimens in this population, with no safety concerns identified. This study evaluated the safety, efficacy, and pharmacokinetics of sofosbuvir-velpatasvir (SOF/VEL) for 12 weeks in patients with HCV infection on dialysis. Method(s): Treatment-naive or -experienced patients, of any genotype, with or without compensated cirrhosis and undergoing hemodialysis or peritoneal dialysis, were enrolled to receive an open-label SOF/VEL (400 mg/100 mg daily) fixed-dose combination once daily for 12 weeks. The primary efficacy end-point was comparison of the sustained virological response 12 weeks after treatment (SVR12) to a prespecified historic control rate of 83%. The primary safety end-point was the proportion of patients who discontinued therapy due to adverse events (AEs). Secondary endpoints included safety, viral resistance, and pharmacokinetics. Result(s): A total of 59 patients were enrolled at 21 sites in Canada, the United Kingdom, Spain, Israel, Australia, and New Zealand. The median age was 60 years (range, 33-91), 59% were male, 53% white, 22% treatment-experienced, and 29% had cirrhosis. Most patients had HCV genotype 1 (42%), 2 (12%), or 3 (27%). Most (92%) were on hemodialysis, with a mean dialysis duration of 7.3 years (range, 0-40). Treatment was well tolerated; no one discontinued therapy due to AEs. One patient was discontinued from therapy on day 74 for non-compliance, with 48% study medication adherence by pill count. Overall, 56/59 patients (95%) achieved SVR12. Two (3%) had virological relapse (one with non-adherence). One patient did not achieve SVR12 due to death from suicide after SVR4. Exposures were consistent with the Phase 1 renal impairment study. The most frequent AEs were headache, fatigue, nausea, and vomiting. Serious AEs occurred in 19% of patients; none was assessed as being related to the study drug. Conclusion(s): Treatment with a SOF/VEL single-tablet regimen for 12 weeks in patients with and without cirrhosis undergoing dialysis resulted in a 95% SVR12 rate. The regimen was safe and well tolerated, with no treatment-related discontinuations or treatment-related serious AEs.