Regulatory Decision Summary for Maviret

Maviret was originally approved as a 12-week regimen in treatment-naïve patients with compensated cirrhosis and HCV GT 1-6 infection. In this SNDS, the recommended duration of therapy with Maviret for these patients (except for HCV GT 3 infection) was shortened to 8 weeks. This change is supported by results from an ongoing Phase 3b, single-arm, open-label, multicenter study (Expedition-8; M16-135), which assessed the efficacy, safety and pharmacokinetics of 8-week treatment with Maviret in 280 treatment-naïve adults with compensated cirrhosis and HCV GT 1 (81.8%), 2 (10%), 4 (4.6%), 5 (0.4%) or 6 (3.2%) infection. Expedition-8 trial also includes treatment-naïve patients with HCV GT 3 infection but the data for these patients was not available at the time of this SNDS.

The primary efficacy endpoint, i.e. sustained virologic response 12 weeks post-treatment (SVR₁₂), was achieved in 97.9% of patients in Expedition-8 trial. This SVR₁₂ was comparable to historical SVR₁₂ rates observed in the registrational trials where patients with compensated cirrhosis were treated with Maviret for 12 weeks. The SVR₁₂ was 97% in patients with HCV GT 1 infection and 100% in patients with HCV GT 2, 4, 5 or 6 infection. There were no on-treatment virologic failures. Six patients did not achieve SVR₁₂; 1 patient discontinued study drug prematurely and 5 patients were lost to follow-up.

The safety profile of Maviret in Expedition-8 trial was generally favourable. The majority of adverse events were Grade 1 in severity. The most common adverse events (≥ 5% of patients) were pruritus, fatigue, headache and nausea. Nine patients experienced Grade ≥ 3 adverse events and six patients experienced serious adverse events; none of these events was considered to be related to Maviret. There were no discontinuations from the trial due to adverse events.

The pharmacokinetic analysis demonstrated that the exposure (Ctrough) of glecaprevir and pibrentasvir in patients participating in Expedition-8 trial were generally similar to the exposure reported previously in HCV-infected patients with compensated cirrhosis treated with Maviret for 12 weeks.

Health Canada considers that the submitted data support the change in recommended treatment duration for treatment-naïve patients with compensated cirrhosis and HCV GT 1, 2, 4, 5 or 6 infection. No data were submitted for treatment-naïve patients with compensated cirrhosis and HCV GT 3 infection and therefore, the recommended treatment duration for these patients remains unchanged (i.e. 12 weeks). The overall benefit-harm-uncertainty profile of Maviret remains favourable when used as directed in the Maviret Product Monograph.