IDDF2019-ABS-0136 Sofosbuvir/velpatasvir for 12 weeks is safe and effective in patients undergoing dialysis

Background Approved HCV treatments for patients on dialysis are associated with complexities including drug-drug interactions, baseline resistance testing and use of ribavirin. Despite higher concentrations of the primary circulating sofosbuvir (SOF) metabolite, GS-331007, in severe renal impairment, real-world cases demonstrated substantial use of SOF-based regimens in this population without safety concerns identified. This study evaluated the safety, efficacy, and pharmacokinetics (PK) of SOF/velpatasvir (VEL) for 12 weeks in patients with HCV infection on dialysis. Methods Treatment-naive or -experienced patients, of any genotype, with or without compensated cirrhosis undergoing hemodialysis or peritoneal dialysis, were enrolled to receive open-label SOF/VEL (400/100 mg) once daily for 12 weeks. The primary efficacy endpoint was a comparison of the SVR12 to a prespecified historic control rate of 83%. The primary safety endpoint was the proportion of patients who discontinued therapy due to adverse events (AEs). Secondary endpoints included safety, viral resistance and PK. Results 59 patients were enrolled at 21 sites in Canada, United Kingdom, Spain, Israel, Australia and New Zealand. The median age was 62 years (range 49–86), 59% were male, 53% white, 32% treatment experienced, 29% had cirrhosis. Most patients had HCV genotype 1 (42%), or 3 (27%). Most (92%) were on hemodialysis with a mean dialysis duration of 7.3 years. Treatment was well tolerated; no one discontinued therapy due to AEs. One patient was discontinued therapy on day 74 for non-compliance with 48% study medication adherence by pill count. Overall, 56/59 (95%) of patients achieved SVR12. Two (3%) had virologic 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 related to study drug. Conclusions Treatment with SOF/VEL 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 SAEs.