The FDA has approved the first combination pill to treat chronic hepatitis C virus (HCV) infection. This drug is also the first approved regimen that does not require administration with interferon or ribavirin.
The pill combines ledipasvir and sofosbuvir, 2 drugs that interfere with the enzymes HCV needs to multiply. Ledipasvir, a new drug, is an HCV NS5A inhibitor; sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor.
The recommended dose is 1 tablet taken once daily with or without food. The recommended treatment is 12 weeks for treatment-naïve patients with or without cirrhosis; 12 weeks for treatment-experienced patients (ie, those who have not responded to peginterferon alfa in combination with ribavirin or an HCV protease inhibitor combined with peginterferon alfa and ribavirin) without cirrhosis; and 24 weeks for treatment-experienced patients with cirrhosis. An 8-week treatment can be considered for treatment-naïve patients without cirrhosis who have pretreatment HCV RNA < 6 million IU/mL.
The fixed-dose combination (ledipasvir 90 mg, sofosbuvir 400 mg) was evaluated in 3 clinical trials involving 1,518 patients who had not previously received treatment for their infection or who had not responded to previous treatment. Participants were randomly assigned to receive the combination pill with or without ribavirin. In the first trial of treatment-naïve patients, 202 of 215 patients (94%) who received ledipasvir-sofosbuvir for 8 weeks and 208 of 216 patients (96%) who received it for 12 weeks achieved sustained virologic response (SVR). In the second trial, 99% of patients with and without cirrhosis achieved SVR after 12 weeks.
The third trial evaluated efficacy in treatment-experienced participants with and without cirrhosis. In the 12-week arm, 102 of 109 patients (94%) achieved SVR, as did 108 of 109 patients (99%) in the 24-week arm. In all the trials, ribavirin did not increase response rates.
This is the seventh new drug designated as breakthrough therapy to receive FDA approval. It was reviewed under the priority review program, which expedites review of drugs that treat serious conditions and could significantly improve safety or effectiveness.
FDA Hepatitis Update—Approval of Harvoni fixed-dose combination tablet (ledipasvir and sofosbuvir) for treatment of Hepatitis C. Silver Spring; MD: U.S. Food and Drug Administration; 2014.
FDA approves first combination pill to treat hepatitis C [news release]. Silver Spring, MD: U.S. Food and Drug Administration; October 10, 2014.