Sa1497 - The Safety and Tolerability of SOF/VEL/VOX for 8 or 12 Weeks in > 1,000 Patients Treated in the POLARIS-1, POLARIS-2, POLARIS-3, and POLARIS-4 Studies: An Integrated Analysis

Abstract

Background The once-daily fixed-dose combination tablet of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) was evaluated for the treatment of genotype 1–6 HCV infection in four phase 3 studies in patients with and without compensated cirrhosis. This analysis describes the safety of SOF/VEL/VOX across 4 Phase 3 studies. Methods Treatment-emergent adverse events (AEs) and laboratory abnormalities were assessed in patients who received SOF/VEL/VOX or placebo for 12 weeks (POLARIS-1), SOF/VEL/VOX or SOF/VEL for 12 weeks (POLARIS-4), or SOF/VEL/VOX for 8 weeks or SOF/VEL for 12 weeks (POLARIS-2 and POLARIS-3). SAEs and deaths were followed until post-treatment Week 24. Data were pooled by treatment regimen. Results 1056 patients were treated with SOF/VEL/VOX for 8 (n=611) or 12 (n=445) weeks, 700 received SOF/VEL for 12 weeks. 38% had compensated cirrhosis, 28% had a BMI≥30 kg/m2, 36% were female, and 12% were ≥65 years old. AEs are presented in the table. Two deaths were reported, one illicit drug overdose and one attributed to hypertension (on post-treatment Day 76), neither were related to treatment. SAEs and discontinuations were more frequent in the placebo group and occurred with similar frequency in the other groups; none were related to study treatment. Headache, fatigue, nausea, and diarrhoea were the most common AEs. Mild diarrhoea and nausea occurred more frequently in the SOF/VEL/VOX groups. Overall, 5.1%–6.6% of patients who received SOF/VEL/VOX or SOF/VEL had Grade 3 or 4 laboratory abnormalities. Among patients receiving VOX, one patient each had a Grade 3 elevation in ALT and bilirubin (table 1). Conclusions SOF/VEL/VOX for 8 or 12 weeks in the POLARIS studies was well tolerated with a low frequency of Grade 3 or 4 AEs, SAEs, and AEs leading to discontinuation. The frequency of AEs in the SOF/VEL/VOX groups was similar to SOF/VEL and placebo groups, with higher rates of mild diarrhoea and nausea compared to SOF/VEL.