FDA Approves Expanded Pediatric Indication for Gilead's Epclusa (Sofosbuvir/Velpatasvir) to Treat Children Aged 3 and Older with Chronic Hepatitis C

June 14, 2021 /BioonBIOON/ -- Gilead Sciences recently announced that the U.S. Food and Drug Administration (FDA) has approved an expanded pediatric indication for the hepatitis C drug Epclusa (sofosbuvir/velpatasvir), to include pediatric patients with chronic hepatitis C aged ≥3 years, regardless of HCV genotype or severity of liver disease.

FDAApprovedEpclusa: A New Oral Granule Formulation（sofosbuvir/velpatasvir，200mg/50mg，150mg/37.5mg），This formulation is specifically developed for young children unable to swallow tablets.Regarding dosing, the recommended dose of Epclusa in children aged ≥3 years is based on body weight and liver function.

Notably,Epclusa is the only protease inhibitor-free, pan-genotypic HCV treatment regimen approved for the treatment of HCV patients as young as 3 years old.In the United States, as of 2018, approximately 35,400–60,500 children were infected with HCV, with an increasing incidence rate. Mother-to-child transmission is the most common cause of HCV infection in children, representing a 161% increase from 2009 to 2017. Among women of reproductive age, intravenous drug use is the primary driver of HCV infection.

Epclusa is the world's first all-oral, pan-genotypic, single-tablet hepatitis C treatment regimen. Administered once daily, it is indicated for the treatment of patients with all six hepatitis C genotypes (GT-1, -2, -3, -4, -5, -6). The drug consists of Gilead's previously marketed blockbuster hepatitis C drug Sovaldi (sofosbuvir) and another antiviral agent, velpatasvir. Specifically, sofosbuvir is a nucleotide analog polymerase inhibitor, while velpatasvir is a pan-genotypic NS5A inhibitor. Notably, the Epclusa prescribing label carries a boxed warning indicating the risk of hepatitis B virus (HBV) reactivation in patients with HCV/HBV co-infection.

Epclusa was approved for marketing in June 2016. With this latest approval, the drug is indicated for children and adults aged ≥3 years with chronic hepatitis C virus (HCV) genotype 1–6 infection: (1) Epclusa monotherapy for 12 weeks for patients without cirrhosis or with compensated cirrhosis (Child-Pugh class A); (2) Epclusa in combination with ribavirin (RBV) for 12 weeks for patients with decompensated cirrhosis (Child-Pugh class B or C).

This approval is based on a Phase II open-labelClinical Trialdata. The trial enrolled 41 pediatric patients aged 3 to 6 years who received 12 weeks of Epclusa treatment. Results showed that,At 12 weeks after completion of treatment, the virologic cure rate (SVR12) by viral genotype for the 12-week Epclusa regimen was: 88% (28/32) in patients with HCV genotype 1 infection, 50% (3/6) in patients with genotype 2 infection, 100% (2/2) in patients with genotype 3 infection, and 100% (1/1) in patients with genotype 4 infection.。Among the 7 patients who were not cured, all discontinued treatment within 1 to 20 days after treatment initiation.

In this study, the safety of Epclusa in children aged 3 to <6 years and adultsClinical TrialThe results were generally consistent. Vomiting and product use issues (spitting out the medication) were reported in 15% and 10% of pediatric patients, respectively; theseAdverse ReactionsVery mild (Grade 1 or 2), resulting in treatment discontinuation in 5 pediatric patients (12%).

Dr. Merdad Parsey, Chief Medical Officer of Gilead Sciences, stated: "Gilead remains firmly committed to supporting the elimination of hepatitis C virus (HCV)."FDAToday’s decision expands curative treatment options for children infected with HCV, representing a significant step forward toward this goal. This approval adds to the robust clinical evidence supporting the safety and efficacy of Epclusa across a broad patient population, including those with end-stage renal disease and fibrosis of all stages.”

Gilead Sciences has developed four generations of products for hepatitis C, all of which have been approved for marketing in China:

——On September 25, 2017, Sovaldi (Suohuadi; generic name: sofosbuvir, 400 mg tablets) was approved, in combination with other drugs, for the treatment of pan-genotypic (genotypes 1–6) hepatitis C virus (HCV) infection in adults and adolescents aged 12 to 18 years; this approval made Sovaldi (Suohuadi) Gilead Sciences’ first hepatitis C treatment officially approved in China;

——On May 30, 2018, Epclusa (丙通沙; generic name: sofosbuvir/velpatasvir; 400 mg/100 mg tablets) was approved for the treatment of adult patients with chronic hepatitis C virus (HCV) infection of genotypes 1–6, mixed genotypes, or unknown genotypes. This approval made Epclusa (丙通沙) China’s first pan-genotypic single-tablet regimen for HCV.

——On December 4, 2018, Harvoni (Xiafanning, ledipasvir/sofosbuvir, ledipasvir 90 mg/sofosbuvir 400 mg) was approved for the treatment of adult and adolescent patients aged 12 to 18 years with chronic hepatitis C virus (HCV) genotype 1–6 infection.

——On December 18, 2019, Vosevi (sofosbuvir/velpatasvir/voxilaprevir, SOF/VEL/VOX, 400 mg/100 mg/100 mg) was approved for the re-treatment of adult patients with chronic hepatitis C virus (HCV) infection who had previously failed one direct-acting antiviral (DAA) therapy, without cirrhosis or with compensated cirrhosis.

Among the four aforementioned hepatitis C medications, Sovaldi is commonly known as “Gilead Gen 1,” Harvoni as “Gilead Gen 2,” Epclusa as “Gilead Gen 3,” and Vosevi as “Gilead Gen 4.” Of these, Vosevi (“Gilead Gen 4”) is the world’s first once-daily single-tablet regimen approved for use as salvage therapy in specific hepatitis C patients, and it also represents the final addition to Gilead’s sofosbuvir (SOF)-based HCV direct-acting antiviral (DAA) pipeline.

It is worth noting that the U.S. prescribing information for four of these drugs includes a boxed warning indicating that the drug may pose a risk of hepatitis B virus (HBV) reactivation in patients co-infected with hepatitis C virus/hepatitis B virus (HCV/HBV). (Bioon.com)

Original Source:U.S. Food and Drug Administration Approves New Formulation of Epclusa?, Expanding Pediatric Indication to Treat Children Ages 3 and Older With Chronic Hepatitis C