Hepatology publishes six-year data demonstrating improved clinical outcomes in patients with Alagille syndrome treated with Livmarli (maralixibat) – Mirum Pharma

Mirum Pharmaceuticals, Inc. announced that Hepatology published an analysis demonstrating a statistically significant improvement in six-year event-free and transplant-free survival in patients with Alagille syndrome (ALGS) treated with Livmarli (maralixibat) oral solution when compared with a natural history control group (p<0.0001).

The analysis evaluated time to clinical outcome from the pooled Livmarli clinical studies versus a control cohort from the Global Alagille Alliance (GALA) clinical database, the largest global ALGS natural history database.

“Patients with Alagille syndrome often undergo liver transplantation for complications related to cholestasis,” said Binita M. Kamath, MBBChir, Staff Physician and Senior Associate Scientist, The Hospital for Sick Children (SickKids), Toronto, Ontario, Canada, and senior author of the manuscript. “This seminal six-year analysis of Livmarli versus a comparable natural history control group demonstrates a 70% risk reduction for clinical outcomes in patients treated with Livmarli.”

The pre-specified statistical analysis was conducted independently by the lead author Dr. Bettina Hansen, Professor of Clinical Biostatistics at Erasmus MC, Netherlands and compared time to first clinical event in the Livmarli-treated patients with ALGS (n=84) versus a well-selected external natural history cohort treated with standard of care from the GALA database (n=469). Events were defined as liver transplantation, biliary diversion surgery, manifestations of portal hypertension, or death. The GALA control group was identified based on a pre-specified and blinded selection process to align with eligibility criteria from the Livmarli clinical studies. Multiple sensitivity and subgroup analyses were conducted to ensure statistical robustness of the primary result.

Data from the analysis demonstrated a significant improvement in six-year event-free survival with a p-value of <0.0001 (HR: 0.305, 95% CI: 0.189-0.491) translating to a 70% overall reduction for clinical outcomes with Livmarli. The analysis also showed statistically significant improvements in transplant-free survival (liver transplantation or death) as compared to the GALA cohort with a p-value of <0.0001 (after adjusting for age, sex, total bilirubin, and ALT) (HR: 0.332; 95% CI 0.197-0.559). Sensitivity and subgroup analyses demonstrated overall consistency with the primary results.

See- “Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA”- Hansen, Bettina E.; Vandriel, Shannon M.; Vig, Pamela; Garner, Will; Mogul, Douglas B.; Loomes, Kathleen M.; Piccoli, David A.; Rand, Elizabeth B.; Jankowska, Irena; Czubkowski, Piotr; Gliwicz-Miedzi?ska, Dorota; et al., ; The Global ALagille Alliance (GALA) Study Group Hepatology ():10.1097/HEP.0000000000000727, December 25, 2023. | DOI: 10.1097/HEP.0000000000000727.