Gilead's Epclusa Achieves 92-95% SVR12 Rates in Pediatric Hepatitis C Patients Aged 6-18

Approved treatment options for children under 12 years of age with hepatitis C virus (HCV) infection, particularly those with HCV genotypes 2 and 3, are limited. In an open-label study involving pediatric patients aged 6 to 18 years with HCV genotypes 1, 2, 3, 4, and 6, the 12-week Epclusa regimen achieved a virologic cure rate (SVR12) of 95% (97/102) in patients aged 12 to <18 years and 92% (67/73) in patients aged 6 to <12 years.

In the study, the majority of adverse events were mild or moderate in severity. Four patients experienced serious adverse events, one of which was attributed to the treatment. The most common adverse events (occurring in >15% of patients) were headache, fatigue, and nausea in adolescent patients, and vomiting, cough, and headache in pediatric patients aged 6 to 12 years. Currently, the study is ongoing in pediatric patients with hepatitis C aged 3 to <6 years. In the aforementioned pediatric populations, the use of Epclusa is investigational, and its safety and efficacy have not been established.

Epclusa is the world’s first all-oral, pan-genotypic, single-tablet regimen for hepatitis C, administered once daily for the treatment of patients with all six genotypes (GT-1, -2, -3, -4, -5, -6) of hepatitis C. The drug combines Gilead’s already marketed blockbuster hepatitis C medication Sovaldi (sofosbuvir) with another antiviral agent, velpatasvir. Sofosbuvir is a nucleotide analog polymerase inhibitor, while velpatasvir is a pan-genotypic NS5A inhibitor.

In the United States, Epclusa is indicated for chronic hepatitis C virus (HCV) genotype 1–6 infection: (1) Epclusa monotherapy for 12 weeks in patients with HCV without cirrhosis or with compensated cirrhosis (Child-Pugh class A); (2) Epclusa in combination with ribavirin (RBV) for 12 weeks in patients with HCV and decompensated cirrhosis (Child-Pugh class B or C); and (3) in patients coinfected with HCV and human immunodeficiency virus (HIV).

Gilead: Fourth-generation hepatitis C product; third-generation approved for market launch in China

Gilead has developed four generations of products for hepatitis C, three of which have been approved for marketing in China: (1) On September 25, 2017, Sovaldi (Sohuadi; generic name: sofosbuvir, 400 mg tablets) was approved for use in combination with other drugs to treat genotype 1–6 hepatitis C virus (HCV) infection in adults and adolescents aged 12–18 years. This approval made Sovaldi the first HCV treatment drug formally approved by Gilead in China; (2) On May 30, 2018, Epclusa (Bingtongsha; generic name: sofosbuvir/velpatasvir, 400 mg/100 mg tablets) was approved for the treatment of adult patients infected with chronic HCV of genotypes 1–6, mixed genotypes, or unknown genotypes. This approval made Epclusa the first pan-genotypic single-tablet regimen for HCV in China; (3) On December 4, 2018, Harvoni (Xiafanning; ledipasvir 90 mg/sofosbuvir 400 mg) was approved for the treatment of adult and adolescent patients (aged 12–18 years) with chronic hepatitis C virus (HCV) infection of genotypes 1–6.

Among the three aforementioned hepatitis C medications, Sovaldi is commonly known internationally as "the first-generation JI," Harvoni as "the second-generation JI," and Epclusa as "the third-generation JI." "The fourth-generation JI" refers to Vosevi (SOF/VEL/VOX, sofosbuvir/velpatasvir/voxilaprevir tablets), which is the world’s first once-daily single-tablet regimen approved as a salvage therapy for specific hepatitis C patients. It also represents the final product in Gilead Sciences’ pipeline of sofosbuvir-based direct-acting antiviral (DAA) drugs for hepatitis C virus (HCV).

Vosevi consists of two components from Gilead’s marketed pan-genotypic hepatitis C cocktail therapy, Epclusa (SOF/VEL), and voxilaprevir; among these, SOF is a nucleoside analog polymerase inhibitor, VEL is a pan-genotypic NS5A inhibitor, and voxilaprevir is a pan-genotypic NS3 protease inhibitor.

On June 12 this year, the marketing application for Vosevi (sofosbuvir/velpatasvir/voxilaprevir tablets) in China was accepted, with the acceptance number JXHS1900078. This drug has been included in the first batch of urgently needed overseas new drugs published by the National Medical Products Administration.