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, caused by HCV genotypes 1, 2, 3, 4, 5, or 6 infections, without cirrhosis or with compensated cirrhosis and in combination with ribavirin in decompensated cirrhosis.

The recommended treatment regimen for patients without cirrhosis or with compensated cirrhosis is one tablet of Epclusa once daily for 12 weeks, and for patients with decompensated cirrhosis it is one tablet once daily plus daily ribavirin for 12 weeks.

The primary efficacy and safety data supporting this indication are derived from three Phase III studies in chronic hepatitis C patients without cirrhosis or with compensated cirrhosis, and in one Phase III study in patients with decompensated cirrhosis.

Epclusa is a fixed-dose combination treatment with pangenotypic activity. The efficacy of Epclusa 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. Epclusa is highly effective in all patient populations with compensated liver disease. The overall SVR12 rate across the three trials was 98% for patients with chronic hepatitis without cirrhosis or with compensated cirrhosis. The efficacy and safety data in patients with genotype 1 and 3 infection and decompensated liver disease (Child-Pugh B) indicate good activity of Eplusa plus ribavirin for 12 weeks. There are limited clinical data on which to base an assessment of efficacy for patients with HCV genotypes 2, 4, 5, or 6 and with decompensated cirrhosis. The overall SVR12 rate in patients with HCV and decompensated cirrhosis was 94% (82/87) for the group treated with Epclusa plus ribavirin for 12 weeks.

The simplified treatment regimen of Epclusa and its pangenotypic activity provides a new option in the treatment of HCV.

Epclusa is a well-tolerated regimen without significant toxicities or drug-drug interactions, and may thus simplify on-treatment monitoring.

Clinically relevant safety signals have not been identified with administration of Epclusa in the populations studied. The uncertainties of Epclusa include a lack of efficacy and safety data in patient populations that have not yet been evaluated, including patients with HCV and human immunodeficiency virus 1 co-infection, 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 product labelling 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 flares in patients co-infected with HCV and HBV, and an increase in cases of early liver cancer recurrence - 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 Epclusa Product Monograph at this time.

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