Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Adolescents with Chronic HCV: Part 1 of the DORA Study

Jonas, Maureen M Squires, Robert H Rhee, Susan M Lin, Chih-Wei Bessho, Kazuhiko Feiterna-Sperling, Cornelia Hierro, Loreto Kelly, Deirdre Ling, Simon C Strokova, Tatiana del Valle-Segarra, Antonio Lovell, Sandra Liu, Wei Ng, Teresa I Porcalla, Ariel Gonzalez, Yuri Sanchez Burroughs, Margaret Sokal, Etienne [UCL] et al.[show all]

The pangenotypic regimen of glecaprevir and pibrentasvir (G/P) is approved to treat adults with chronic hepatitis C virus (HCV) infection, and has yielded high cure rates in adults in clinical trials. Approved treatment options for pediatrics may include ribavirin (RBV). A pangenotypic regimen for pediatric patients remains an unmet need. DORA is an ongoing phase 2/3, non-randomized, open-label study evaluating the pharmacokinetics (PK), safety, and efficacy of G/P in pediatric patients with chronic HCV. This analysis includes Part 1 of the study, conducted in adolescent patients 12-17 years old given the adult regimen of G/P (300 mg/120 mg) once-daily for 8-16 weeks according to the indication durations used in adults. Patients were either treatment-naïve or experienced with interferon (IFN)- based regimens. The primary PK endpoint was steady-state exposures for glecaprevir and pibrentasvir; the primary efficacy endpoint was sustained virologic response 12 weeks post-treatment (SVR12). The secondary efficacy endpoints were on-treatment virologic failure, relapse, and reinfection. Safety and tolerability were monitored. Part 1 enrolled 48 adolescent patients infected with genotypes 1, 2, 3, or 4; 47 of whom were administered G/P. All 47 patients (100%) achieved SVR12. No on-treatment virologic failures or relapses occurred. PK exposures of glecaprevir and pibrentasvir were comparable to exposures in adults. No AEs led to treatment discontinuation, and no serious AEs occurred. CONCLUSION: Adolescent patients with chronic HCV infection treated with G/P achieved a comparable exposure to adults, 100% SVR12 rate, and safety profile consistent with that in adults. This is the first pangenotypic regimen to demonstrate 100% efficacy within the adolescent population in as little as 8 weeks of treatment.