Sofosbuvir/velpatasvir for 12 weeks results in high SVR12 rates with a favorable safety profile in asian patients: an integrated subgroup analysis of the ASTRAL-1, ASTRAL-2, and ASTRAL-3 studies

Abstract

Background: Sofosbuvir (SOF)/velpatasvir (VEL) 400/100 mg for 12 weeks resulted in an overall 98% sustained virologic response rates 12 week after treatment completion (SVR12) with a favorable safety profile in genotype (GT) 1–6 HCV-infected patients in the SOF/VEL phase 3 clinical development program conducted in North America, Western Europe, Australia, New Zealand, and Hong Kong. Here we compare the safety and efficacy of SOF/VEL in Asian versus non-Asian patients enrolled and treated in these 3 Phase 3 SOF/VEL registrational trials. Methods: An integrated analysis of ASTRAL-1 (SOF/VEL for 12 weeks versus placebo in patients with GT1, 2, and 4–6 HCV infections), ASTRAL-2 (SOF/VEL for 12 weeks versus SOF + ribavirin for 12 weeks in patients with GT2 HCV infections), and ASTRAL-3 (SOF/VEL for 12 weeks versus SOF + ribavirin for 24 weeks in patients with GT3 HCV infections) was performed. Selfreported race collected at baseline was used to categorize patients as either Asian or non-Asian, and patients who did not disclose race were excluded. Efficacy was determined by the proportion of patients achieving SVR12. Safety was assessed by ascertainment of adverse events (AEs) and monitoring of laboratory parameters. Result: In ASTRAL-1, 2, and 3, there were 86 (2% GT1a, 14% GT1b, 7% GT2, 27% GT3, 4% GT4, and 47% GT6) Asian and 944 (22% GT1a, 11% GT1b, 24% GT2, 27% GT3, 12% GT4, 4% GT5, and 1% GT6) non-Asian patients who received SOF/VEL for 12 weeks. Asians tended to be younger [mean (SD) age 47 (12.1) versus 54 (10.7) years] with lower BMIs [24.9 (4.1) versus 26.9 (5.1) kg/m2 ], relative to non-Asian patients. The proportions of patients with compensated cirrhosis were 22 and 21%, treatment experience were 16 and 29%, and IL28B CC genotype were 65 and 30% for Asian and non-Asian patients, respectively. SVR12 was achieved in 99% of Asian and 98% of non-Asian patients (Table 1). The one Asian patient failing to achieve SVR12 had GT3 infection and was lost to follow-up. Of note, 100% of the seven Asian patients with GT3 infection and cirrhosis achieved SVR12 compared to 90% (66/73) of non-Asian patients. SOF/VEL was generally safe and well tolerated among Asian patients who had no discontinuations due to AEs, and fewer overall AEs [54 (63%)] and Grade 3 or above AEs [2 (2%)] compared with non-Asian patients [764 (81%) and 30 (3%), respectively]. The four serious AEs in Asian patients were all considered unrelated to treatment. Asians had 1 or more Grade 3 or above laboratory abnormality less frequently than non-Asians [5 (6%) versus 72 (8%)]. Conclusion: SOF/VEL was highly effective in Asian patients with an overall SVR12 rate of 99% and no Asian patients experiencing virologic failure. SOF/VEL was well tolerated among Asian patients with no one prematurely discontinuing treatment due to AEs.