FDA Approves Maralixibat for Treatment of Pediatric Patients With PFIC


The drug is indicated for patients 5 years of age and older with progressive familial intrahepatic cholestasis and cholestatic pruritus in pediatric patients with Alagille syndrome.

About the Trial

Trial Name: A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC) (MARCH-PFIC)

ClinicalTrials.gov ID: NCT03905330

Sponsor: Mirum Pharmaceuticals, Inc.

Completion Date: September 1, 2022

The FDA has approved maralixibat (Limarli; Mirum Pharmaceuticals) for the treatment of cholestatic pruritus in patients with progressive familial intrahepatic cholestasis (PFIC). This approval is indicated for patients who are 5 years of age and older, and an additional supplemental new drug application for the drug was also submitted to the FDA with the intention of introducing a higher concentration of the treatment.

Maralixibat is a once-daily oral solution that is an ileal bile acid transporter (IBAT) inhibitor and the only FDA-approved drug for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) who are 3 months of age or older, and for patients with PFIC who are 5 years of age and older. It is also approved in Europe for patients who are 2 months and older, in Canada, and other regions. Maralixibat received a breakthrough therapy designation for ALGS and PFIC type 2, and an orphan drug designation for ALGS and PFIC.

“[Maralixibat] has the potential to have a transformational impact for patients with cholestatic pruritus associated with PFIC, and importantly, offers an option for those patients with the rarest of subtypes,” said Chris Peetz, chief executive officer at Mirum, in a press release.

The approval comes after data from the phase 3 MARCH (NCT03905330) study, the largest randomized trial that enrolled 93 patients with different genetic PFIC types—including PFIC1, PFIC2, PFIC3, PFIC4, PFIC6, and an unidentified mutational status—to test the safety and efficacy of maralixibat in pediatric patients. For this trial, patients were randomly assigned to receive either 600 mcg/kg of oral maralixibat twice a day for 26 weeks (n = 47), or an oral placebo of the same dose twice a day for 26 weeks (n = 46). The primary outcome measure for the trial was the mean change in the average morning ItchRO severity score.

“[Maralixibat]’s approval in cholestatic pruritus for patients with PFIC is a result of years of investigation and a collection of a strong body of clinical evidence showing meaningful improvements across a number of important parameters, including pruritus, affecting children with PFIC,” said study investigator Richard Thompson, professor of molecular hepatology at King’s College London, BM, BCh, in the press release. “I am pleased that we will have a well-studied and efficacious option to offer patients whose life has been disrupted by itch.”

Potential adverse effects (AEs) of maralixibat include liver injury, gastrointestinal complications, and fat soluble vitamin deficiency. During the study, commonly reported AEs included diarrhea, abdominal pain, vomiting, constipation, infections, pyrexia, cough, and skin complications. The investigators also recommend that maralixibat should not be taken by patients with PFIC2 who also have severe defects in their bile salt export pump protein.

“PFIC is a difficult disease for both the patient and family and significantly impedes the quality of life for all. These young and fragile patients endure an itch so severe that they experience deficits in their sleep, nutrition, growth, and, in the past, some have turned to transplant to resolve their itch,” said Emily Ventura, executive director of the PFIC Network and mom to a daughter with PFIC, in the press release. “We are hopeful that [maralixibat] will have a measurable impact for patients, potentially offering a new normal and relief from the sleepless nights and disruption to their lives caused by cholestatic pruritus."1

1. Businesswire. Mirum Pharmaceuticals’ LIVMARLI Receives FDA Approval for Treatment of Cholestatic Pruritus in Patients with Progressive Familial Intrahepatic Cholestasis. News release. March 13, 2024. Accessed March 14, 2024. https://www.businesswire.com/news/home/20240313135184/en
2. A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC) (MARCH-PFIC).ClinicalTrials.gov identifier: NCT03905330. Updated December 11, 2023. Accessed March 14, 2024. https://www.clinicaltrials.gov/study/NCT03905330
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