Regulatory Decision Summary for Maviret

Health Canada considers that the benefit/risk profile of Maviret is favourable for use as directed in the treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection with or without compensated cirrhosis. This includes patients with HCV genotype 1 infection who were previously treated with either a regimen of NS5A inhibitor or with a NS3/4A protease inhibitor but not both classes of inhibitors.

Maviret is an immediate release fixed dose combination tablet containing 100 mg of glecaprevir (GLE) and 40 mg of pibrentasvir (PIB) for administration once daily with food. The recommended dose is 300/120 mg or three 100/40 mg tablets for Treatment-Naive and Treatment-Experienced (peginterferon/ribavirin plus sofosbuvir or Direct Acting Antiviral) adult patients with or without compensated cirrhosis for 8-, 12-, or 16-weeks.

The primary efficacy and safety information reported in support of the Maviret was derived from nine Phase 2 and Phase 3 clinical trials made-up of open-labeled, placebo controlled, and active controlled clinical studies.

Maviret is a fixed dose combination with pangenotypic activity for the treatment of HCV infection. The efficacy of Maviret was assessed by measuring the sustained virologic response rates at follow-up Week 12 (SVR12) across all HCV genotypes in different subsets of patients infected with HCV. Maviret is also designed to address areas of previously unmet medical needs such as renally impairment patients and patients with a history of prior treatment failures with Direct Acting Antivirals (DAAs). The minimal renal elimination of the drug substances offered the opportunity to develop an effective and well-tolerated DAA regimen for GT-2, GT-3, GT-5, and GT-6 infected patients with Chronic kidney disease (CKD) Stages 4 - 5 that could be used without dose adjustment. In these severe cases of renally impaired patients (GFR <30 mL/min/1.73 m²), including those on dialysis, the virologic cure rate (SVR12) product has been found to be very high (98%) for the recommended treatment duration. In addition, Maviret regimen demonstrated high SVR rates in patients who failed previous treatments with DAA regimens (patients previously exposed to NS3 and NS5A but not to patients previously exposed to both classes of inhibitors), in GT-3 infected patients, patients with NS5A Y93H mutation at baseline. Maviret also offers short treatment duration (8-weeks) for patients infected by genotypes 1-6 without cirrhosis.

The risks associated with Maviret include the potential use of contraindicated and not recommended drugs, post-market appearance of resistance associated variants, HBV reactivation during and post-treatment of HCV. The efficacy determination for Maviret was based on a very limited number of GT-5, 6 patients. In addition, pediatric patients, pregnant women, and post-liver transplant patients were not included and there were a very limited number of HCV-HIV co-infected patients in the conduct of the clinical trials. Overall, the risk profile of Maviret is considered to be manageable through proper product labelling.

Maviret is well-tolerated and shown to have a favorable safety profile. The overall benefit-risk balance of the regimen supports its use in patients with chronic HCV genotypes 1 to 6 with compensated liver disease, including patients with renal impairment and patients previously treated with DAAs for the recommended treatment duration.

The overall benefit-risk profile for the Maviret is favorable when used as directed in the prescribing information for the treatment of adult patients across HCV genotypes 1 to 6, treatment durations (8, 12, or 16-weeks), prior treatment history, including patients with baseline polymorphism and patients with comorbidities (e.g. cirrhosis, renal impairment).

For more information on Health Canadas decision, please view the Summary Basis of Decision.