Gilead's Epclusa (Sofosbuvir/Velpatasvir) Receives EU Approval for Pediatric Use in Children Aged ≥6 Years and Weighing ≥17 kg

September 03, 2020 News /BioonBIOON/ -- Gilead Sciences’ hepatitis C drug Epclusa (Chinese brand name: Bingtongsha; generic name: sofosbuvir/velpatasvir, 400 mg/100 mg tablets) has recently received positive regulatory news in the European Union! The European Commission (EC) has approved an expansion of Epclusa’s marketing authorization for the treatment of pediatric patients aged ≥6 years and weighing ≥17 kg with chronic hepatitis C, regardless of HCV genotype or severity of liver disease.

A spokesperson for Gilead Sciences stated that Epclusa is a pangenotypic, pan-fibrotic treatment regimen. This approval simplifies the selection of appropriate therapeutic options and eliminates the need for certain pre-treatment assessments, therebyDiagnosisMinimize the time from treatment initiation to cure.

In the United States, Epclusa was approved in March 2020FDAApproved for use in the same pediatric populations mentioned above. Regarding dosing, the recommended dose of Epclusa in children aged ≥6 years is based on body weight and hepatic function. Notably, Epclusa is the first pan-genotypic, protease inhibitor-free regimen approved for the treatment of hepatitis C in both adult and pediatric patients.

Hepatitis C virus (HCV) is a life-threatening virus affecting tens of thousands of children in Europe. If left untreated, it can lead to severe liver complications, includingLiver Cancer。

Epclusa is the world’s first all-oral, pangenotypic, pan-fibrosis, single-tablet regimen for the treatment of hepatitis C, administered once daily for patients with all six genotypes (GT-1, -2, -3, -4, -5, -6). The drug comprises Gilead’s marketed blockbuster hepatitis C medication Sovaldi (sofosbuvir) and another antiviral agent, velpatasvir. Sofosbuvir is a nucleotide analog polymerase inhibitor, while velpatasvir is a pangenotypic NS5A inhibitor. Notably, the Epclusa prescribing information includes a boxed warning indicating the risk of hepatitis B virus (HBV) reactivation in patients co-infected with hepatitis C virus (HCV) and hepatitis B virus (HBV).

Epclusa was approved for marketing in June 2016. With this latest approval, the drug is indicated for children and adults aged ≥6 years and weighing ≥17 kg with chronic hepatitis C virus (HCV) genotype 1–6 infection: (1) Epclusa monotherapy for 12 weeks is indicated for patients without cirrhosis or with compensated cirrhosis (Child-Pugh class A); (2) Epclusa in combination with ribavirin (RBV) for 12 weeks is indicated for patients with decompensated cirrhosis (Child-Pugh class B or C). (3) For patients co-infected with HCV and human immunodeficiency virus (HIV), as well as those with renal impairment (including end-stage renal disease requiring dialysis), the dosing regimen should follow option (1) or (2) based on the status of cirrhosis.

Regulatory Approval of Epclusa for the Treatment of Pediatric Patients, Based on a Phase II Open-LabelClinical Trials(Study 1143) data. This trial enrolled 175 pediatric patients who received 12 weeks of Epclusa treatment, with 173 included in the efficacy analysis. The results showed that among pediatric patients aged 6 to 18 years with HCV genotypes 1, 2, 3, 4, and 6, the virologic cure rate (SVR12) for the 12-week Epclusa regimen was 95% (97/102) in patients aged 12 to under 18 years, and 92% (67/73) in patients aged 6 to under 12 years.

By viral genotype: (1) In children aged 12 to less than 18 years, the cure rate with the 12-week Epclusa regimen was 93% (71/76) in patients with HCV genotype 1 infection, and 100% in those with HCV genotype 2 (6/6), genotype 3 (12/12), genotype 4 (2/2), and genotype 6 (6/6) infections. (2) In children aged 6 to 12 years, the cure rate with the 12-week Epclusa regimen was 93% (50/54) in patients with HCV genotype 1 infection, 91% (10/11) in those with HCV genotype 3 infection, and 100% in those with HCV genotype 2 (2/2) and genotype 4 (4/4) infections.

In this study, the safety of Epclusa treatment in children aged 6 years and older was comparable to that in adultsClinical TrialThe results were largely consistent. The most common adverse reactions in adults treated with Epclusa for 12 weeksAdverse Reactions(Incidence ≥10%, all grades) are headache and fatigue.

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 (Sohuadi; generic name: sofosbuvir; 400 mg tablets) was approved for use in combination with other drugs to treat genotype 1–6 hepatitis C virus infection in adults and adolescents aged 12–18 years. This approval made Sovaldi (Sohuadi) the first hepatitis C treatment drug formally approved by Gilead Sciences in China.

—On May 30, 2018, Epclusa (Chinese brand name: Bingtongsha; 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 (Bingtongsha) the first pan-genotypic, single-tablet regimen for HCV in China.

— On December 4, 2018, Harvoni (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) infection of genotypes 1–6.

—On December 18, 2019, Vosevi (sofosbuvir/velpatasvir/voxilaprevir, SOF/VEL/VOX; sofosbuvir/velpatasvir/voxilaprevir, 400 mg/100 mg/100 mg) was approved for the re-treatment of chronic hepatitis C virus (HCV) infection in adults who had previously failed treatment with a direct-acting antiviral (DAA) regimen and who have no cirrhosis or have compensated cirrhosis.

Among the four aforementioned hepatitis C medications, Sovaldi is commonly known as “Ji Yi Dai,” Harvoni as “Ji Er Dai,” Epclusa as “Ji San Dai,” and Vosevi as “Ji Si Dai.” Notably, Vosevi (“Ji Si Dai”) is the first globally approved once-daily single-tablet regimen for use as a salvage therapy in specific hepatitis C patients, and it also represents the final product in Gilead Sciences’ portfolio of sofosbuvir (SOF)-based direct-acting antiviral (DAA) drugs for hepatitis C virus (HCV).Notably, the U.S. labeling for four of these drugs includes a boxed warning indicating that they may pose a risk of hepatitis B virus (HBV) reactivation in patients coinfected with hepatitis C virus (HCV) and HBV.

In August this year, the Chinese package insert for Epclusa (丙通沙) was updated, recommending no dose adjustment of Epclusa for patients with any degree of renal impairment, including those requiring dialysis. The Chinese package insert for Harvoni (夏帆宁) was also updated, stating that no dose adjustment of Harvoni is required for patients with any degree of renal impairment, including end-stage renal disease (ESRD) patients undergoing dialysis. (Bioon.com)

Original Source: EU OKs Paediatric Use of Gilead's Epclusa