Regulatory Decision Summary for Harvoni

Health Canada considers that the benefit/risk profile of Harvoni is favourable when used as directed in the treatment of adult patients with chronic Hepatitis C virus (HCV) genotypes 2, 3, 4, 5, or 6 without cirrhosis or with compensated cirrhosis; HCV genotype 4 and HIV-1 co-infection; HCV genotype 4 in liver transplant recipients with or without compensated cirrhosis and an alternate dosing regimen for use in HCV genotype 1 patients.

The primary efficacy and safety data supporting this indication are derived from three Phase II studies in chronic hepatitis C (CHC) patients without cirrhosis or with compensated cirrhosis, two Phase II studies in liver transplant recipients with CHC without cirrhosis, with compensated cirrhosis and decompensated cirrhosis and one Phase III study in CHC patients with HCV/HIV-1 co-infection without cirrhosis or with compensated cirrhosis.

Harvoni is a fixed-dose combination treatment with pangenotypic activity. The efficacy of Harvoni 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. Harvoni is highly effective in all patient populations with compensated liver disease. The overall SVR12 rate across genotypes 2, 4, 5 and 6 was 98% for patients with chronic hepatitis without cirrhosis or with compensated cirrhosis. The overall SVR12 rate for Harvoni and ribavirin for genotype 3 was 100% for patients with chronic hepatitis without cirrhosis or 82% with compensated cirrhosis, and 100% in liver transplant recipients without cirrhosis and 75% in liver transplant recipients with compensated cirrhosis.

The simplified treatment regimen of Harvoni and its pangenotypic activity provides another option in the treatment of HCV. Harvoni has been available for the treatment of HCV genotype 1, and is a well-tolerated regimen without significant toxicities or drug-drug interactions.

The recommended treatment regimen for genotypes 2, 4, 5, or 6 patients without cirrhosis or with compensated cirrhosis is one tablet of Harvoni once daily for 12 weeks, and for patients with genotype 3 or liver transplant recipients it is one tablet once daily plus daily ribavirin for 12 weeks.

No new clinically relevant safety signals have been identified with administration of Harvoni in the populations studied. The uncertainties of Harvoni include limited amount of efficacy and safety data in certain patient populations, preventing dosing recommendations, notably in patients with HCV and hepatitis B virus (HBV) co-infection, and patients with severe hepatic impairment (Child-Pugh C) or a lack of efficacy and safety data in patients with severe renal impairment.

Potential risks (as seen with the class of direct acting antivirals in the treatment of HCV) include: post-treatment hepatitis B flares in patients co-infected with HCV and HBV, and an increase in cases of hepatocellular carcinoma thought to be due to the rapid effect on the immune system caused by the treatment with the directly acting antivirals.

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