dm+d

33621411000001107

New Medicines

EpclusaHepatitis C infection - chronic in children and adolescents aged 6 to 17 years

Information

Epclusa
Licence extension / variation
Gilead Sciences
Gilead Sciences

Development and Regulatory status

Launched
Launched
Launched
December 2020
Dec 20Launched in the EU. Pack size 28 film-coated 200/50 mg tablets cost £12,993.33 [7].
Sep 20Approved in EU [6].
Jun 20Recommended for EU approval by CHMP - the full indication is now "the treatment of chronic hepatitis C virus (HCV) infection in patients aged 6 years and older and weighing at least 17 kg." The CHMP also recommended the addition of a new 200/50 mg strength for the film-coated tablets [5]
Mar 20Approved in US for children aged 6 years and over weighing at least 17 kg, regardless of HCV genotype or liver disease severity [4].

Category

Viral hepatitis (05.03.03)
A once-daily, fixed-dose combination (FDC) tablet containing GS 5816 and sofosbuvir for the treatment of chronic hepatitis C. GS 5816 is a pan-genotypic NS5A inhibitor + sofosbuvir is a second-generation nucleotide analogue that inhibits the NS5B protein
Prevalence of HCV in children and adolescents aged <16 years is 0.8% [1].
Hepatitis C infection - chronic in children and adolescents aged 6 to 17 years
Oral

Trial or other data

PII study (NCT03022981) is ongoing but has completed recruitment
PII study starts (NCT03022981). The study will have 2 parts: Pharmacokinetics (PK) Lead-in Phase and the Treatment Phase. The primary objective of the PK Lead-in Phase is to evaluate the steady state PK and confirm the dose of sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination (FDC) in pediatric participants with chronic hepatitis C virus (HCV) infection. The primary objective of the Treatment Phase is to evaluate the safety and tolerability of SOF/VEL for 12 weeks in pediatric participants with chronic HCV. 217 patients aged 3 to 17 years will be recruited in the US, Belgium, Italy & UK. Collection of primary outcome data is expected to complete Oct 19 [2].
PII trial complete - no data yet available. [3]

Evidence based evaluations

EpclusaChronic hepatitis C infection in children aged 3 to under 6 years (and new granule formulation)

Information

Epclusa
New formulation and licence extension / variation
Gilead Sciences
Gilead Sciences

Development and Regulatory status

Approved (Licensed)
Approved (Licensed)
Approved (Licensed)
May 22MHRA approves a licence change for Epclusa 200/50mg and 400/100mg tablets to extend use to children from age of 3 years (previously only for children aged 6 years and older). The new indication is treatment of chronic hepatitis C virus (HCV) infection in patients 3 years of age and older. MHRA also approves a new granule formulation for paediatric patients having difficulty swallowing film-coated tablets. Available as 150/37.5mg coated granules in sachet and 200/50mg coated granules in sachet, and also licensed for treatment of chronic hepatitis C virus (HCV) infection in patients 3 years of age and older [8].
Jan 22EMA approves new granule formulations, and licence change to extend use to children from age of 3 years [7].
Nov 21The proposed new indication in the EU is treatment of chronic hepatitis C virus (HCV) infection in patients aged 3 years of age and older [6].
Nov 21EU positive opinion granted recommending a licence change to include use in children aged 3 years of age and older (previously licensed only for in patients 6 years of age and older weighing at least 17kg). CHMP also recommend addition of 150/37.5mg coated granules in sachet and 200/50mg coated granules in sachet [6].
Jun 21Two strengths of a new oral pellet formulation suitable for younger children unable to swallow tablets approved in the US, along with an expansion of the indication for sofosbuvir/velpatasvir to include children as young as 3 years regardless of HCV genotype or liver disease severity [5].

Category

A once-daily, fixed-dose combination (FDC) tablet containing GS 5816 and sofosbuvir for the treatment of chronic hepatitis C. GS 5816 is a pan-genotypic NS5A inhibitor + sofosbuvir is a second-generation nucleotide analogue that inhibits the NS5B protein
Prevalence of HCV in children and adolescents aged <16 years is 0.8% [1].
Chronic hepatitis C infection in children aged 3 to under 6 years (and new granule formulation)
Oral

Further information

Yes

Trial or other data

Jun 21US approval for children as young as 3 years of age is based on data from a PII, 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 7 patients who did not achieve cure, all discontinued treatment within 1 to 20 days of starting treatment. The safety profile of Epclusa in children 3 to less than 6 years of age treated was generally consistent with that observed in clinical trials in adults. Vomiting and product use issue (spitting up the drug) were reported in 15% and 10% of subjects, respectively; these adverse reactions were mild (Grade 1 or 2) and led to treatment discontinuation in 5 (12%) subjects [5].
Oct 20Results of PII trial (NCT03022981) posted. The study was designed to assess pharmacokinetic outcomes but did look at efficacy as secondary outcomes. The percentage of pts with Sustained Virologic Response (SVR) at 12 weeks after discontinuation of therapy (SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL). SVR12 was 82.9% in those 3 to < 6 years old vs. 93.2% in those 6-12 years old and 95.1% in those aged 12-18. [5]
Feb 20PII trial complete - no data yet available. [3]
Jun 19PII study (NCT03022981) is ongoing but has completed recruitment
Jan 17PII study starts (NCT03022981). The study will have 2 parts: Pharmacokinetics (PK) Lead-in Phase and the Treatment Phase. The primary objective of the PK Lead-in Phase is to evaluate the steady state PK and confirm the dose of sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination (FDC) in pediatric participants with chronic hepatitis C virus (HCV) infection. The primary objective of the Treatment Phase is to evaluate the safety and tolerability of SOF/VEL for 12 weeks in pediatric participants with chronic HCV. 217 patients aged 3 to 17 years will be recruited in the US, Belgium, Italy & UK. Collection of primary outcome data is expected to complete Oct 19 [2].

Evidence based evaluations