Mirum Publishes Phase 3 MARCH Data on LIVMARLI for PFIC in The Lancet

In a significant breakthrough for the treatment of progressive familial intrahepatic cholestasis (PFIC), Mirum Pharmaceuticals, Inc. has announced the publication of data from their Phase 3 MARCH-PFIC study. The study, which evaluated LIVMARLI® (maralixibat) oral solution in patients with PFIC, was published in The Lancet Gastroenterology and Hepatology. This study marks the largest randomized, double-blind, placebo-controlled investigation into PFIC, confirming the efficacy and safety of LIVMARLI across a broad range of genetic PFIC types.

The MARCH-PFIC study assessed the drug’s impact on two main groups: those with BSEP deficiency (PFIC2) and the All-PFIC cohort, which included patients with BSEP (PFIC2), FIC1 (PFIC1), MDR3 (PFIC3), TJP2 (PFIC4), and MYO5B deficiencies. The study successfully met its primary efficacy endpoint, which was the mean change in pruritus severity score between baseline and the last 12 weeks of treatment (weeks 15-26). Additionally, it achieved its key secondary endpoint, which was the mean change in total serum bile acid concentration between baseline and the average of weeks 18, 22, and 26. Statistically significant improvements were observed as early as Week 2, continuing throughout the 26-week study period in LIVMARLI-treated participants across both cohorts.

The study also reported notable improvements in multiple parameters such as bilirubin concentrations, growth, and sleep disturbances in participants treated with LIVMARLI compared to those on placebo. Importantly, no new safety concerns emerged during the treatment periods, with the most common adverse event being mild and transient diarrhea.

This Phase 3 study presents the most comprehensive dataset to date, demonstrating the therapeutic benefits of an IBAT inhibitor across the widest array of PFIC types ever studied. Beyond the clinical benefits, LIVMARLI significantly improved serum bile acids and bilirubin levels, which are both indicators of transplant-free survival. These findings highlight LIVMARLI as a non-surgical, pharmacological option that can significantly improve outcomes for PFIC patients.

Dr. Alexander Miethke from Cincinnati Children’s Hospital, the lead author of the publication, emphasized that the data enhance the understanding of LIVMARLI’s potential to provide meaningful improvements in pruritus and other parameters impacting PFIC patients. The clinically meaningful reductions in serum bile acid and bilirubin levels suggest potential benefits in native liver survival, marking a step forward in long-term care for PFIC patients.

Pam Vig, PhD, Chief Scientific Officer and Head of Research at Mirum, expressed satisfaction with the recognition of these findings by The Lancet. She noted that patients with PFIC suffer from cholestasis, which can lead to severe pruritus, poor growth, and progressive liver disease. The data underscore the significant impact LIVMARLI can have in this severe cholestatic setting.

LIVMARLI is an orally administered, once-daily ileal bile acid transporter (IBAT) inhibitor. It is approved by the U.S. Food and Drug Administration for treating cholestatic pruritus in patients with Alagille syndrome (ALGS) aged three months and older, and in PFIC patients aged five years and older. The European Commission and Health Canada have also approved LIVMARLI for treating cholestatic pruritus in ALGS patients. Mirum Pharmaceuticals has submitted LIVMARLI for approval in Europe for treating PFIC in patients aged two months and older.

Mirum Pharmaceuticals, Inc., dedicated to treating rare diseases, has other approved medications like CHOLBAM® and CHENODAL®. They continue to develop treatments for liver diseases, with promising results from ongoing clinical trials.

This pioneering study underscores the potential of LIVMARLI to provide significant clinical benefits and improve the quality of life for patients with various types of PFIC.