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FDA Approves Harvoni, Gilead's Sofosbuvir/Ledipasvir Combo Pill for Hepatitis C


On October 10, the U.S. Food and Drug Administration (FDA) approved a new once-daily combination pill for the treatment of genotype 1 chronic hepatitis C containing Gilead Sciences' HCV nucleotide polymerase inhibitor sofosbuvir (Sovaldi) plus ledipasvir, the first approved HCV NS5A inhibitor.

Harvoni, which contains 400 mg sofosbuvir and 90 mg ledipasvir, is taken as a single pill once-daily. Duration of treatment is 12 weeks for previously untreated (treatment-naive) people with or without liver cirrhosis and for patients without cirrhosis who were not cured with prior interferon-based therapy. Treatment-experienced people with cirrhosis should be treated for 24 weeks. Some easier-to-treat patients may be able to cut treatment duration to just 8 weeks.

Sofosbuvir/ledipasvir is the first approved hepatitis C single-tablet regimen and the first approved all-oral combination that can be used without ribavirin, which can cause anemia and should not be used by pregnant women due to risk of birth defects. (Sofosbuvir plus simeprevir [Olysio] is recommended by expert guidelines for people who cannot take interferon, but this regimen is not FDA approved.)

In clinical trials sofosbuvir/ledipasvir produced high rates of sustained virological response (SVR) at 12 weeks after completing treatment, considered to be a cure. The combination was evaluated in clinical trials that enrolled more than 1500 treatment-naive participants and prior non-responders, including people with cirrhosis. In the Phase 3 ION trials, SVR rates for sofosbuvir/ledipasvir taken for 8, 12, or 24 weeks, with or without ribavirin, ranged from 94% to 99%. This combination was more effective against HCV genotype 1 than dual therapy with sofosbuvir plus ribavirin alone.

"By providing very high cure rates in as little as 8 weeks and completely eliminating the need for interferon and ribavirin, which are challenging to take and tolerate, Harvoni significantly advances treatment for patients with the most common form of hepatitis C in the United States," ION investigator Nezam Afdhal of Beth Israel Deaconess Medical Center stated in a Gilead press release. "For the first time, the vast majority of patients can be cured with a once-daily pill in only eight or 12 weeks."

Sofosbuvir/ledipasvir is generally safe and well-tolerated. The most common side effects in clinical trials were fatigue and headache. Sofosbuvir and ledipasvir may interact with other drugs including certain anti-convulsants, anti-TB drugs, and a few antiretrovirals for HIV, but in general interactions are manageable and most HIV/HCV coinfected people should be able to construct effective regimens with non-interacting antiretrovirals.

"With the development and approval of new treatments for hepatitis C virus, we are changing the treatment paradigm for Americans living with the disease," Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, stated in the FDA press release. "Until last year, the only available treatments for hepatitis C virus required administration with interferon and ribavirin. Now, patients and health care professionals have multiple treatment options, including a combination pill to help simplify treatment regimens."

According to the Centers for Disease Control and Prevention, about 3.2 million Americans are infected with HCV, and without effective treatment 15% to 30% will go on to develop complications such as cirrhosis or liver cancer.

Gilead has previously said that it expects the price for Harvoni to be around $95,000-$100,000 for a 12-week course, compared with $84,000 for Sovaldi alone. The company says this price is similar to the previous standard of care, pegylated interferon/ribavirin plus one of the first-generation HCV protease inhibitors, boceprevir (Victrelis) or telaprevir (Incivek). Adding $10,000-$15,000 for the ledipasvir component means Gilead should be able to undercut other companies' drugs that might be used with sofosbuvir instead, such as Janssen's simeprevir or Bristol-Myers Squibb's daclatasvir.

To assist eligible patients in the U.S., Gilead has added Harvoni to its patient assistance and co-pay programs (

Full prescribing information for Harvoni is available online at


U.S. Food and Drug Administration. FDA Approves First Combination Pill to Treat Hepatitis C. Press release. October 10, 2014.

R Klein, K Struble, and S Morin, FDA. FDA Hepatitis Update - Approval of Harvoni fixed-dose combination tablet (ledipasvir and sofosbuvir) for treatment of Hepatitis C. October 10, 2014.

Gilead Sciences. U.S. Food and Drug Administration Approves Gilead’s Harvoni (Ledipasvir/Sofosbuvir), the First Once-Daily Single Tablet Regimen for the Treatment of Genotype 1 Chronic Hepatitis C. Press release. October 10, 2014.