General Information

Epclusa is a fixed-dose combination of sofosbuvir, a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor, and velpatasvir, an HCV NS5A inhibitor.

Epclusa is specifically indicated for the treatment of adults and pediatric patients 3 years of age and older with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection:

• without cirrhosis or with compensated cirrhosis
• with decompensated cirrhosis for use in combination with ribavirin

Epclusa is supplied as tablets for oral administration, as well as oral pellets for use by younger children who cannot swallow tablets.

Adults: The recommended dosage is one tablet (400 mg of sofosbuvir and 100 mg of velpatasvir) taken orally once daily with or without food for 12 weeks. For patients with moderate to severe cirrhosis (decompensated cirrhosis), Epclusa is approved for use in combination with the drug ribavirin. The recommended dose for patients as young as 6 years of age or weighing at least 17 kg, regardless of HCV genotype or liver disease severity is based on weight and liver function. 

Pediatrics: The recommended dosage of Epclusa in pediatric patients 3 years of age and older is based on weight. Administer Epclusa oral pellets or tablets once daily with or without food. In pediatric patients less than 6 years of age, administer the oral pellets with food to increase tolerability related to palatability. 

Mechanism of Action

Epclusa is a fixed-dose combination of sofosbuvir and velpatasvir. Sofosbuvir is an inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is required for viral replication. Velpatasvir is an inhibitor of the HCV NS5A protein, which is required for viral replication. Resistance selection in cell culture and cross-resistance studies indicate velpatasvir targets NS5A as its mode of action.

Side Effects

Adverse effects associated with the use of Epclusa may include, but are not limited to, the following:

• headache
• fatigue

Adverse effects associated with the use of Epclusa with ribavirin may include, but are not limited to, the following:

• fatigue
• anemia
• nausea
• headache
• insomnia
• diarrhea

The Epclusa drug label comes with the following Black Box Warning: : RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV. Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with Epclusa . HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.

Clinical Trial Results

The FDA approval of Epclusa was based on three Phase III clinical trials of 1,558 subjects without cirrhosis or with compensated cirrhosis (mild cirrhosis). Results demonstrated that 95 to 99 percent of patients who received Epclusa had no virus detected in the blood 12 weeks after finishing treatment, suggesting the patients' infections had been cured. The safety and efficacy of Epclusa was also evaluated in a clinical trial of 267 subjects with decompensated cirrhosis (moderate to severe cirrhosis), of whom 87 subjects received Epclusa in combination with ribavirin for 12 weeks. 94 percent of these patients had no virus detected in the blood 12 weeks after finishing treatment.

The approval of Epclusa for patients as young as 6 years of age or weighing at least 17 kg, regardless of HCV genotype or liver disease severity was based on data from a Phase 2, open-label clinical trial (Study 1143) that enrolled 175 children who were treated with Epclusa for 12 weeks, of which 173 were included in the efficacy analysis. In children 12 to <18 years old, treatment with Epclusa resulted in a cure rate (SVR12) of 93 percent (71/76) in those with genotype 1 HCV infection and 100 percent in those with genotype 2 (6/6), genotype 3 (12/12), genotype 4 (2/2) and genotype 6 (6/6) HCV infection. In children 6 to <12 years old, the SVR rate was 93 percent (50/54) in those with genotype 1 HCV infection, 91 percent (10/11) in those with genotype 3 HCV infection, and 100 percent in those with genotype 2 (2/2) and genotype 4 (4/4) HCV infection.

The approval of Epclusa for children as young as 3 years of age is based on data from a Phase 2, open-label clinical trial that enrolled 41 children 3 years to less than 6 years of age to be treated with Epclusa for 12 weeks. At 12 weeks after treatment completion, Epclusa achieved a sustained virologic response (SVR12) or cure rate of 83% (34/41) among all patients, 88% (28/32) in children with HCV genotype 1, 50% (3/6) in children with HCV genotype 2, and 100% in children with HCV genotype 3 (2/2) and HCV genotype 4 (1/1). Of the seven patients who did not achieve cure, all discontinued treatment within one to 20 days of starting treatment.