Regulatory Decision Summary for Maviret
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
The purpose of this Supplemental New Drug Submission for Maviret was to expand the treatment indication to include adolescent patients 12 years and older with chronic hepatitis C virus infection. This SNDS was filed under the Priority Review Policy.
Why was the decision issued?
Health Canada considers that the benefit-harm-uncertainty profile of Maviret is favourable when used as directed in the treatment of chronic hepatitis C virus (HCV) infection in patients 12 years or older. Maviret is a fixed dose combination (FDC) tablet formulation of glecaprevir (GLE)/pibrentasvir (PIB) (100/40 mg).
The pediatric indication is based on the results of a Phase 2/3, open-label, multicenter study which assessed the efficacy, pharmacokinetics, safety and tolerability of Maviret in 47 subjects 12 to < 18 years old with genotypes 1-4 HCV infection, without compensated cirrhosis and who were either treatment-naïve (TN) or treatment-experienced (TE) to interferon (IFN) with or without ribavirin (RBV). All subjects achieved sustained virologic response 12 weeks post-treatment (SVR12). There was no relationship between weight and Maviret exposure or age and Maviret exposure. GLE and PIB exposures were similar between HCV-infected adolescents and HCV-infected adults. The safety profile of Maviret was favourable with no reported deaths, serious adverse events (SAEs), Grade 3 or higher adverse events (AEs), or study drug discontinuations due to an AE or liver-related toxicities. The AE profiles for Maviret treatment were similar between adolescents and adults as reported in Phase 3 studies for adults.
The harms associated with the use of Maviret include clinically significant interactions between Maviret and a number of drugs, which can lead to loss of therapeutic effectiveness, increased risk of myopathy, including rhabdomyolysis or alanine transferase (ALT) elevations. The use of Maviret also carries a risk of Hepatitis B (HBV) reactivation.
There is uncertainty about the safety and efficacy of Maviret in adolescents infected with HCV genotypes 5 or 6, those with compensated cirrhosis and those previously treated with a regimen containing sofosbuvir, as these subpopulations were not included in the Phase 2/3 study. The known harms and uncertainties associated with Maviret use are manageable through the inclusion of appropriate warnings and cautionary statements in the Maviret Product Monograph.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.