The fixed-dose oral antiviral combination (containing ledipasvir 90mg and sofosbuvir 400mg) is indicated for use as monotherapy in adult patients with genotype 1 or 4 chronic hepatitis C without cirrhosis or with compensated cirrhosis. A single tablet should be taken once daily with or without food for eight to 24 weeks in patients without cirrhosis and for 12 to 24 weeks in those with compensated cirrhosis.
Harvoni may also be used in combination with ribavirin for patients with genotype 1 or 4 chronic hepatitis C with decompensated cirrhosis or who are pre-/post-liver transplantation and in genotype 3 patients with cirrhosis and/or prior treatment failure. Treatment duration in these patient groups is 24 weeks.
Ledipasvir targets the HCV NS5A protein, which is involved in hepatitis C (HCV) RNA replication and the assembly of HCV virions. Sofosbuvir (available separately as Sovaldi) inhibits the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication.
The efficacy of ledipasvir/sofosbuvir with or without ribavirin was evaluated in three open-label phase III studies involving 1,950 patients with genotype 1 chronic hepatitis C. The primary endpoint in all three studies was sustained virologic response (SVR), defined as HCV RNA <25iu/ml at 12 weeks after the end of treatment.
The ION-1 study evaluated ledipasvir/sofosbuvir with or without ribavirin for 12 or 24 weeks in 865 treatment-naive adults with or without cirrhosis. The SVR rate in the monotherapy groups was 99% and 98% for the 12- and 24-week regimens, respectively, compared with 97% and 99% for the ribavirin 12- and 24-week regimens, showing no benefit for the addition of ribavirin or for the use of 24-week therapy.
Patients in the ION-2 study (n=440) were randomised to the same four treatment regimens as in ION-1 but were adults with or without cirrhosis who had failed prior therapy with an interferon-based regimen. The SVR rate was greater for the two 24-week regimens (99% for both), and lower for the 12-week monotherapy regimen than for the 12-week ribavirin regimen (94% versus 96%).
In the ION-3 study, 647 treatment-naive adults without cirrhosis were randomised to receive ledipasvir/sofosbuvir as monotherapy for eight or 12 weeks or combined with ribavirin for eight weeks. The SVR rate was 94% and 96% in the eight-week and 12-week monotherapy groups, respectively, and 93% in the ribavirin group, demonstrating that no additional benefit was conferred by adding ribavirin or continuing treatment for 12 weeks.
Harvoni was well tolerated in clinical studies with headache and fatigue the only commonly reported adverse effects.
Further information: Gilead