Ledipasvir‐Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C

Abstract

For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct‐acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir‐sofosbuvir in HCV‐infected children aged 3 to <6 years. In an open‐label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight‐based doses of combined ledipasvir‐sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naïve. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event “abnormal drug taste.” The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir‐sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection.

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…Three clinical trials supporting the approval of ledipasvir/sofosbuvir in the pediatric population aged ≥ 3 years demonstrated high SVR12 rates comparable to those observed in adults. (281)(282)(283) Limited real-world data further corroborate these findings. (284,285) In September 2019, the FDA approved weightbased sofosbuvir plus ribavirin for treatment-naive and interferon-experienced (± ribavirin) children aged ≥ 3 years with genotype 2 or 3, without cirrhosis or with compensated cirrhosis (Child-Pugh A).…”

“…A 12‐week course is recommended for patients without cirrhosis; 24 weeks is recommended for those with compensated cirrhosis. Three clinical trials supporting the approval of ledipasvir/sofosbuvir in the pediatric population aged ≥ 3 years demonstrated high SVR12 rates comparable to those observed in adults . Limited real‐world data further corroborate these findings …”

Hepatitis C Virus Treatment in Children: A Challenge for Hepatitis C Virus Elimination

“…40,81,82 A large phase II and III, open-label, multicenter, multicohort study evaluated the safety and the efficacy of sofosbuvir (a potent NS5B polymerase inhibitor) and ledipasvir (an NS5A inhibitor). [83][84][85]…”

“…Results of the same association are available for children aged 6 to 11 years 83 and for those aged 3 to 5 years (►Table 3). 84 Treatment duration was 12 weeks for all except one patient with HCV genotype 1 infection who was treatment-experienced and cirrhotic and two patients with HCV genotype 3 infection who received 24 weeks of therapy. 2 The pharmacokinetic analyses showed that the "half strength" dosing resulted in plasma concentration generally within the range of those observed in adults.…”

Viral hepatitis

“…Paediatric trials of several combinations of all oral therapy have been published (Table ) . Some of these regimens have been licenced by the US Food and Drug Administration (FDA) and European Medicines Agency in 2017 for children older than 12 years.…”