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FDA Approves Ledipasvir/Sofosbuvir (Harvoni), a Once-Daily, Single-Tablet Regimen for Chronic Hepatitis C
The FDA has approved ledipasvir/sofosbuvir (Harvoni, Gilead Sciences, Inc.), the first once-daily, single-tablet regimen for the treatment of chronic hepatitis C genotype 1 infection in adults.
The product combines 90 mg of the NS5A inhibitor ledipasvir with 400 mg of the nucleotide analog polymerase inhibitor sofosbuvir (Sovaldi, Gilead). The combination’s efficacy has been established in patients with chronic hepatitis C virus (HCV) genotype-1 infection, with a treatment duration of 8, 12, or 24 weeks, depending on the patient’s prior treatment history, cirrhosis status, and baseline viral load. Eight weeks of treatment with ledipasvir/sofosbuvir can be considered for treatment-naïve patients without cirrhosis who have a baseline HCV viral load below 6 million IU/mL.
The FDA’s approval was supported by data from three phase III studies (ION-1, ION-2, and ION-3). These trials evaluated 8, 12, and 24 weeks of treatment with ledipasvir/sofosbuvir, with or without ribavirin, in nearly 2,000 genotype-1 HCV patients with compensated liver disease. These studies included noncirrhotic treatment-naïve patients (ION-3); cirrhotic and noncirrhotic treatment-naïve patients (ION-1); and cirrhotic and noncirrhotic patients who failed prior therapy with an interferon-based regimen, including regimens containing an HCV protease inhibitor (ION-2). The primary endpoint for each study was the sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12).
Patients who achieve SVR12 are considered to be cured of HCV. In these studies, ribavirin was not shown to increase response rates. Trial participants in the ribavirin-free arms (n = 863) achieved SVR12 rates of 94% to 99%.
Among patients treated for 8, 12, or 24 weeks, adverse events led to treatment discontinuation in 0, less than 1%, and 1%, respectively. Fewer adverse events were observed in the ribavirin-free arms compared with the ribavirin-containing arms in all ION studies. The most common adverse reactions among patients treated with ledipasvir/sofosbuvir (5% or more) were fatigue, headache, nausea, diarrhea, and insomnia.