Gilead Sciences recently announced that the U.S. Food and Drug Administration (FDA) has approved an expanded pediatric indication for its hepatitis C drug Epclusa (sofosbuvir/velpatasvir), including pediatric patients aged ≥3 years with chronic hepatitis C, regardless of HCV genotype or severity of liver disease.
Notably, Epclusa is the world's first all-oral, pan-genotypic, single-tablet hepatitis C treatment regimen, taken once daily, for the treatment of patients with all six hepatitis C genotypes (GT-1, -2, -3, -4, -5, -6). Epclusa is the only protease inhibitor-free, pan-genotypic HCV treatment regimen approved for the treatment of hepatitis C patients as young as 3 years old.
The FDA has approved a new oral granule formulation of Epclusa (sofosbuvir/velpatasvir, 200mg/50mg, 150mg/37.5mg), specifically developed for young children who cannot swallow tablets. For use in children ≥3 years of age, the recommended dosage of Epclusa is based on weight and liver function.
Epclusa was approved for marketing in June 2016. It consists of Gilead's marketed hepatitis C drug Sovaldi (sofosbuvir) and another antiviral drug, velpatasvir. Sofosbuvir is a nucleoside analog polymerase inhibitor, while velpatasvir is a pangenotypic NS5A inhibitor. It should be noted that the Epclusa drug label includes a boxed warning indicating the risk of hepatitis B virus (HBV) reactivation in patients co-infected with hepatitis C/hepatitis B (HCV/HBV).
With this latest approval, the drug is now indicated for use in children and adults aged ≥3 years with chronic HCV genotypes 1–6 infection: (1) Epclusa monotherapy for 12 weeks in patients with hepatitis C without cirrhosis or with compensated cirrhosis (Child-Pugh A); and (2) Epclusa in combination with ribavirin (RBV) for 12 weeks in patients with decompensated cirrhosis (Child-Pugh B or C).
This approval is based on data from a Phase II open-label clinical trial that enrolled 41 children aged 3–6 years who received Epclusa for 12 weeks. Results showed that, 12 weeks after treatment completion, the virological cure rate (SVR12) of the 12-week Epclusa regimen, categorized by viral genotype, was 88% (28/32) for HCV type 1, 50% (3/6) for HCV type 2, 100% (2/2) for HCV type 3, and 100% (1/1) for HCV type 4. Of the 7 patients who did not achieve a cure, all discontinued treatment within 1–20 days of initiation.
In this study, the safety profile of Epclusa in children aged 3–6 years was generally consistent with the results of the adult clinical trial. Vomiting and product use problems (spitting out medication) occurred in 15% and 10% of pediatric patients, respectively; these adverse reactions were mild (Grade 1 or 2), leading to treatment discontinuation in 5 children (12%).
