The U.S. Food and Drug Administration (FDA) approved Epclusa (sofosbuvir at 400 mg/velpatasvir at 100 mg) on June 28, 2016, to treat adult patients with chronic hepatitis C virus both with and without cirrhosis. For patients with moderate to severe cirrhosis (decompensated cirrhosis), sofosbuvir/velpatasvir is approved for use in combination with the drug ribavirin. The new product is a fixed-dose combination tablet containing sofosbuvir, a drug approved in 2013, and velpatasvir, a new drug, and is the first to treat all six major forms of hepatitis C virus.
Edward Cox, MD
“This approval offers a management and treatment option for a wider scope of patients with chronic hepatitis C,” said Edward Cox, MD, Director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.
There are at least six distinct hepatitis C virus genotypes—genetically distinct groups of the virus. Knowing the genotype helps inform treatment recommendations and the duration of treatment. Approximately 75% of Americans with hepatitis C virus have genotype 1; 20% to 25% have genotypes 2 or 3; and a small number of patients are infected with genotypes 4, 5, or 6.
According to the Centers for Disease Control and Prevention, hepatitis C virus infection becomes chronic in approximately 75% to 85% of cases. Patients who suffer from chronic hepatitis C virus infection over many years may have complications such as bleeding, jaundice, fluid accumulation in the abdomen, infections, liver cancer, and death.
The safety and efficacy of sofosbuvir/velpatasvir for 12 weeks were evaluated in three phase III clinical trials of 1,558 subjects without cirrhosis or with compensated (mild) cirrhosis. Results demonstrated that 95% to 99% of patients who received sofosbuvir/velpatasvir had no virus detected in the blood 12 weeks after finishing treatment, suggesting the patients’ infections had been cured.
The safety and efficacy of sofosbuvir/velpatasvir were also evaluated in a clinical trial of 267 subjects with decompensated (moderate-to-severe) cirrhosis, of whom 87 subjects received sofosbuvir/velpatasvir in combination with ribavirin for 12 weeks. Ninety-four percent of these patients had no virus detected in the blood 12 weeks after finishing treatment.
The most common side effects of sofosbuvir/velpatasvir include headache and fatigue. Combination regimens containing sofosbuvir/velpatasvir and ribavirin are contraindicated for patients for whom ribavirin is contraindicated.
Sofosbuvir/velpatasvir carries a warning for patients and health care providers that symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is used with sofosbuvir in combination with another hepatitis C virus direct-acting antiviral. Coadministration of amiodarone with sofosbuvir/velpatasvir is not recommended. Sofosbuvir/velpatasvir also carries a warning not to use with certain drugs that may reduce the amount of sofosbuvir/velpatasvir in the blood, which could lead to reduced efficacy of sofosbuvir/velpatasvir.
Sofosbuvir/velpatasvir was reviewed under the FDA’s priority review program. ■