Glecaprevir/Pibrentasvir Treatment in Liver or Kidney Transplant Patients With Hepatitis C Virus Infection

Abstract

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. (ClinicalTrials.gov NCT02692703.) (Hepatology 2018; 00:000-000).

© 2018 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.

Figures

Figure 1

MAGELLAN‐2 trial design. Patients received 12 weeks of open‐label, coformulated, once‐daily glecaprevir/pibrentasvir 300/120 mg (administered as three tablets of glecaprevir/pibrentasvir, 100/40 mg each). All patients were followed until week 36 to monitor for safety and HCV RNA. The primary endpoint was SVR12.

Figure 2

Rates of SVR12 following treatment for all patients who received at least one dose of glecaprevir/pibrentasvir. For the overall intention‐to‐treat and modified intention‐to‐treat analyses, 95% CIs were calculated using the normal approximation to the binomial distribution or the Wilson's score method for rates of 100%. For separate intention‐to‐treat analyses of liver and kidney transplant patients, 95% CIs were calculated using the Wilson's score method. Abbreviations: ITT, intention‐to‐treat; LTFU, lost to follow‐up; mITT, modified intention‐to‐treat (excluding patients with nonvirologic failure).

Figure 3

Immunosuppressant dosing from baseline to end of treatment for liver and kidney transplant patients. Median dosages of everolimus (closed circles), sirolimus (closed diamonds), and tacrolimus (closed squares) are plotted using the left y‐axis; median dosages of cyclosporine (closed triangles) are plotted using the right y‐axis. Abbreviation: BL, baseline.