On October 10, the FDA approved Harvoni (Ledipasvir and Sofosbuvir) for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection. Harvoni is the first combination drug approved for the treatment of chronic HCV genotype 1 infection, also known as hepatitis C cocktail therapy. It is also the first approved regimen that does not require interferon or ribavirin, which are also FDA-approved drugs for the treatment of chronic HCV infection. Two of the drugs in Harvoni interfere with enzymes needed for HCV proliferation. sofosbuvir is a previously approved HCV drug marketed under the trade name Sovaldi. harvoni also includes a new drug, Ledipasvir. “With the development and approval of hepatitis C therapeutics, we are changing the treatment paradigm for hepatitis C patients in the United States,” said Cox, M.D., M.P.H., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “Until last year, the only available drugs for hepatitis C treatment required the use of interferon and ribavirin. Now, patients and health care professionals have multiple treatment options, including a combination drug to help simplify treatment options.” Harvoni is the third drug approved by the FDA in the past year for the treatment of chronic HCV infection.The FDA approved Simeprevir in November 2013 and Sovaldi in December 2013.Hepatitis C is a viral disease that causes inflammation of the liver, leading to decreased liver function or liver failure. Most people with HCV infection do not develop symptoms of the disease until liver damage becomes apparent, which can take decades. Some people with chronic HCV infection develop scarring and cirrhosis years later, which can lead to complications such as bleeding, jaundice (yellow eyes or skin), liver ascites, infections and liver cancer. According to the Centers for Disease Control and Prevention, about 3.2 million Americans are infected with HCV, and 15-30% of these people will go on to develop cirrhosis without normal treatment. The effectiveness of Harvoni was evaluated in three clinical trials of 1,518 patients who had not previously received treatment for their infection or who had not responded to prior treatment, including patients with cirrhosis. Subjects in the trial were randomized to Harvoni with or without ribavirin. The trial was designed to determine whether hepatitis C virus was still detectable in the blood after completion of 12 weeks of treatment (sustained virologic response, or SVR), which showed that the subjects were cured of HCV infection. In the first trial of previously untreated subjects, 94% of Harvoni-treated patients achieved SVR at 8 weeks of treatment and 96% at 12 weeks of treatment. In the second trial of previously untreated subjects with or without cirrhosis, subjects achieved SVR after 12 weeks of treatment. In all three trials, ribavirin did not increase the response rate of patients. The most common side effects reported by subjects in clinical trials were fatigue and headache. Harvoni is the seventh drug to receive FDA approval as a breakthrough drug. The FDA may designate a drug as a breakthrough drug at the request of the applicant if preclinical evidence demonstrates that the drug provides substantial improvement over existing therapeutic agents for patients with serious or life-threatening disease. Harvoni was completed under the FDA’s Priority Review Program, which provides an expedited review for drugs that treat serious diseases and would provide significant improvements in safety and efficacy if approved. Harvoni and Sovaldi are marketed by Gilead in Foster City, Calif. and Olysio is marketed by Janssen Pharmaceuticals in Liden, N.J.