Well‐tolerated, ribavirin‐free, pangenotypic hepatitis C virus (HCV) treatments for transplant recipients remain a high priority. Once‐daily glecaprevir/pibrentasvir demonstrates high rates of sustained virologic response at 12 weeks posttreatment (SVR12) across all major HCV genotypes (GTs). This trial evaluated the safety and efficacy of glecaprevir/pibrentasvir for patients with chronic HCV GT1‐6 infection who had received a liver or kidney transplant. MAGELLAN‐2 was a phase 3, open‐label trial conducted in patients who were ≥3 months posttransplant. Patients without cirrhosis who were HCV treatment‐naive (GT1‐6) or treatment‐experienced (GT1, 2, 4‐6; with interferon‐based therapy with or without sofosbuvir, or sofosbuvir plus ribavirin) received glecaprevir/pibrentasvir (300/120 mg) once daily for 12 weeks. The primary endpoint compared the percentage of patients receiving glecaprevir/pibrentasvir with SVR12 to a historic SVR12 rate based on the standard of care. Safety of glecaprevir/pibrentasvir was assessed. In total, 80 liver transplant and 20 kidney transplant patients participated in the trial. Most patients had no or minimal fibrosis (80% had fibrosis scores F0‐F1) and were infected with HCV GT1 (57%) or GT3 (24%). The overall SVR12 was 98% (n/N = 98/100; 95% confidence interval, 95.3%–100%), which exceeded the prespecified historic standard‐of‐care SVR12 threshold of 94%. One patient experienced virologic failure. One patient discontinued because of an adverse event considered to be unrelated to treatment; this patient achieved SVR12. Adverse events were mostly mild in severity, and laboratory abnormalities were infrequent. Conclusion: Once‐daily glecaprevir/pibrentasvir for 12 weeks is a well‐tolerated and efficacious, ribavirin‐free treatment for patients with chronic HCV GT1‐6 infection who have received a liver or kidney transplant. (http://ClinicalTrials.gov NCT02692703.) (Hepatology 2018; 00:000‐000).

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. A pangenotypic regimen for pediatric patients remains an unmet need. DORA is an ongoing phase 2/3, nonrandomized, 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 of age 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‐based regimens. The primary PK endpoint was steady‐state exposures for glecaprevir and pibrentasvir; the primary efficacy endpoint was sustained virologic response 12 weeks after 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, of whom 47 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 adverse events (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 pangenotypic regimen demonstrated 100% efficacy within the adolescent population in as little as 8 weeks of treatment.

Highlights Meta-analysis of real-world data from 12,583 patients taking glecaprevir/pibrentasvir. Glecaprevir/pibrentasvir achieved 96.7% virologic cure overall. Virologic cure was > − 95% across subgroups of interest. Serious adverse events were reported in 1.0% of patients.

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Background and Aims Chronic hepatitis C virus (HCV) infection increases the risk of incident chronic kidney disease (CKD) and progression to end‐stage renal disease (ESRD). Previously available direct‐acting antiviral regimens are not approved for patients with advanced CKD across all HCV genotypes. Methods EXPEDITION‐5 is a phase 3 study to evaluate efficacy and safety of the fixed‐dose combination of glecaprevir and pibrentasvir (G/P) for chronic HCV infection (genotype 1 through 6) in adults without cirrhosis or with compensated cirrhosis and with stage 3b, 4 or 5 CKD. Patients received approved duration of G/P according to HCV genotype, cirrhosis status and prior HCV treatment experience. The primary efficacy endpoint was percentage of patients with sustained virologic response at 12 weeks post‐treatment (SVR12). Results Among the 101 patients enrolled in the study, 24% had predialysis CKD and 76% were on dialysis. Eighty‐four patients were treated with G/P for 8 weeks, 13 patients for 12 weeks and four patients for 16 weeks. Fifty‐five per cent of patients had genotype 1, 27% had genotype 2, 15% had genotype 3 and 4% had genotype 4, and none had genotype 5 or 6 infection. The SVR12 rate was 97% (98/101, 95% confidence interval, 91.6‐99.0). No patients experienced virologic failure. Adverse events (AEs) reported in at least 5% of the patients were pruritus, bronchitis, hypertension and generalized pruritus. Serious AEs were reported in 12% of patients; none related to study drug. Conclusions G/P treatment yielded high SVR12 rates irrespective of the presence of stage 3b, 4 or 5 CKD. No safety signals were detected. Clinicaltrials.gov identifier This Phase 3 clinical trial was funded by AbbVie and registered with http://www.clinicaltrials.gov as NCT03069365 (EXPEDITION‐5).