Regulatory Decision Summary for Epclusa

Health Canada considers that the benefit/risk profile of Epclusa is favourable for use as directed in the treatment of adults with chronic hepatitis C (HCV), caused by genotypes (GT) 1, 2, 3, 4, 5, or 6 infections, without cirrhosis or with compensated cirrhosis, who are co-infected with Human Immunodeficiency Virus (HIV-1).

Epclusa is a fixed dose combination treatment with pangenotypic activity.

The primary efficacy and safety data supporting this indication are derived from a Phase 3 study in chronic hepatitis C patients without cirrhosis or with compensated cirrhosis. The efficacy of Epclusa was assessed by measuring the sustained virologic response rates at follow-up Week 12 (SVR12) across all HCV genotypes co-infected with HIV-1 virus.

The study results demonstrated high SVR12 rates for co-infected patients (HCV/HIV-1) of various subgroups (treatment naive, treatment-experienced, high baseline viral load (HCV ≥ 800,000 IU/mL), race, patients with a non-CC IL-28B allele, and cirrhotic patients, irrespective of the infecting HCV genotype.

Overall, no patients experienced viral breakthrough on treatment, no patients had detectable HCV RNA at the end of treatment, no patients relapsed during and post-treatment, and no patients discontinued treatment because of adverse events.

There were no new safety signals associated with Epclusa, as there were no deaths, no treatment-related serious adverse events, and no adverse events leading to discontinuation from the study. The safety information from the clinical study has been adequately described in the prescribing information of Epclusa.

The frequencies of Grade 3 to 4 laboratory abnormalities were low among the subjects treated with Epclusa.

The safety profile of Epclusa as an all-oral short treatment duration regimen to treat HCV patients of various genotypes co-infected HIV-1 is favorable and other baseline characteristics (High viral load, cirrhosis).

The uncertainties of Epclusa include a lack of efficacy and safety data in patient populations that have not yet been evaluated include HCV and hepatitis B virus (HBV) co-infection, patients with severe renal impairment, and patients with severe hepatic impairment (Child-Pugh C). Drug-drug interactions may occur with Epclusa and concomitant medications. The proposed product labeling provides a listing of established and potentially significant drug interactions and recommendations.

Potential risks (as seen with the class of direct acting antivirals in the treatment of HCV) include: hepatitis B flare- ups in patients co-infected with HCV and HBV, and an increase in cases of early liver cancer recurrence. The latter is postulated to be based on a disruption of immune surveillance which may facilitate the emergence of metastatic clones.

Based on the data submitted, Health Canada considers that the anticipated benefits of Epclusa outweigh the potential risks under the conditions of use described in the Product Monograph at this time