Regulatory Decision Summary for Epclusa

The safety and efficacy of Epclusa in HCV-infected pediatric patients ≥ 12 years of age and weighing ≥ 30 kg without cirrhosis or with compensated cirrhosis are supported by interim results from a Phase 2, open-label clinical trial GS-US-342-1143 and pharmacokinetic modelling.

Cohort 1 of study GS-US-342-1143 included 102 pediatric patients ≥ 12 years of age who received Epclusa once daily for 12 weeks. Sustained virologic response (SVR12), defined as undetectable HCV RNA at 12 weeks after the cessation of treatment, was the primary endpoint to determine the HCV cure rate. The overall SVR12 rate was 95% (97/102; 95% confidence interval: 88.9% to 98.4%). The SVR12 rate in patients with HCV genotype 1, 2, 3, 4 and 6 were 93% (71/76), 100% (6/6), 100 (12/12), 100% (2/2) and 100 (6/6), respectively. Only one patient who discontinued treatment and subsequently relapsed at Week 4 was considered to be a virologic failure. The other four patients who did not achieve SVR12 did not meet virologic failure criteria (3 subjects were lost to follow-up and 1 subject was pending a post-treatment Week-12 visit).

The pharmacokinetic evaluation in study GS-US-342-1143 or pharmacokinetics-based simulations showed that the exposures of sofosbuvir, GS-331007 (the major metabolite of sobosbuvir) and velpatasvir in HCV-infected pediatric patients ≥ 12 years of age and weighing ≥ 30 kg were similar to those observed in adult patients following administration of Epclusa.

Cohort 1 of study GS-US-342-1143 did not include pediatric patients with HCV genotype 5 and the indication of Epclusa in these patients is based on the extrapolation of the efficacy data from pediatric patients with HCV genotypes 1, 2, 3, 4 and 6. Likewise, Cohort 1 did not include HCV-infected pediatric patients with compensated cirrhosis and the indication of Epclusa in these patients is based on the extrapolation from adults, which was possible due to similar drug exposure in adults and adolescents ≥ 12 years of age and weighing ≥ 30 kg.

Epclusa was well tolerated in Cohort 1 of study GS-US-342-1143. The adverse reactions observed were consistent with those observed in clinical trials of Epclusa in adults. The majority of pediatric patients (75.5%) experienced one or more adverse event. The most commonly reported adverse events were headache (29.4%), fatigue (21.6%), and nausea (16.7%). There were no discontinuations due to adverse events, drug-related serious adverse events or deaths.

Cohort 1 of study GS-US-342-1143 did not include HCV-infected pediatric patients with renal impairment, moderate or severe hepatic impairment, or co-infected with human immunodeficiency virus 1 (HIV-1). Therefore, the Epclusa Product Monograph states that Epclusa has not been studied in these patients.

Based on the review of submitted data, Health Canada considers that the overall benefit-harm-uncertainty profile of Epclusa is favorable in HCV-infected pediatric patients ≥ 12 years of age and weighing ≥ 30 kg when used under the conditions of use described in the Epclusa Product Monograph at this time.