Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Pediatric Patients with Genotypes 1-6 Chronic HCV Infection: Part 1 of the Dora Study

Background: The pangenotypic, direct-acting antivirals glecaprevir (GLE; identified by AbbVie and Enanta) and pibrentasvir (PIB), are coformulated (G/P) and approved to treat adults with chronic HCV infection. G/P achieved high SVR12 rates in Phase 2 and 3 studies, leading to an 8- and 12-week indication in HCV genotype (GT) 1–6 patients without cirrhosis or with compensated cirrhosis, respectively. An approved, pangenotypic pediatric HCV regimen is currently unavailable, and treatment options may include ribavirin (RBV); a pangenotypic regimen with improved tolerability for pediatric patients remains an unmet need. Methods: DORA (NCT03067129) is an ongoing phase 2/3, non-randomized, open-label, multicenter study evaluating the pharmacokinetics (PK), safety, and efficacy of G/P in pediatric patients with chronic HCV infection. This analysis includes only Part 1 of the study, conducted in adolescent patients 12–17 years of age who received the adult formulation of G/P (300 mg/120 mg). Part 2 will be conducted in patients aged 3–11 years given a pediatric formulation of G/P. Patients without cirrhosis or with compensated cirrhosis were either treatment-naïve or experienced with interferon (IFN) with or without RBV, or sofosbuvir plus IFN with or without RBV. In Part 1, the adult formulation of G/P (300 mg/120 mg) was orally dosed once-daily with food for 8, 12 16 weeks. The primary efficacy endpoint was SVR12; the primary PK endpoint was steady-state AUC values for GLE and PIB. The secondary endpoints were Cmax and clearance of GLE and PIB at treatment week 2, and rates of on-treatment virologic failure, relapse, and reinfection. Adverse events and clinical laboratory abnormalities were monitored. Results: Part 1 enrolled 48 adolescent patients; 1 patient was never dosed and thus excluded from this analysis. Table 1 shows baseline demographics. Overall, 47/47 patients (100%) achieved SVR4; 34/34 (100%) patients with available data achieved SVR12. No on-treatment virologic failures or relapses have occurred to date. Intensive PK exposures of GLE and PIB were comparable to exposures in adults. The most common adverse events (AEs) were nasopharyngitis (26%) and upper respiratory tract infection (19%). No AEs led to treatment discontinuation, and no serious AEs occurred. No cases consistent with druginduced liver injury were identified. Conclusion: Adolescent patients with chronic HCV infection treated with G/P achieved high rates of SVR4, without incidence of virologic failure, serious AEs or treatment discontinuation. Final SVR12 and PK data will be presented at the meeting

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

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