FDA Approves Maralixibat to Treat Rare Pediatric Liver Disease

The FDA has approved the first treatment for cholestatic pruritus in patients with Alagille syndrome (ALGS) who are 1 year or older. Maralixibat (Livmarli) is an orally administered, once-daily ileal bile acid transporter inhibitor from Mirum Pharmaceuticals Inc.

ALGS is a rare genetic disorder that causes a bile buildup in the liver and affects 2000 to 2500 children in the United States.

“Children with Alagille syndrome suffer from cholestatic pruritus, which is serious, unremitting, and debilitating. Their sleep is disrupted, and they endure bleeding and scarring of the skin due to unrelenting scratching,” Binita M. Kamath, MBBChir, pediatric hepatologist, The Hospital for Sick Children in Toronto, Ontario, Canada, said in a statement. “There have been no approved treatments to date for cholestatic pruritus in Alagille syndrome, and many children ultimately require major surgical interventions such as liver transplantation for refractory pruritus. The approval of Livmarl signifies a meaningful shift in the treatment paradigm for Alagille syndrome and provides hope for the many families who have lived with persistent itch for far too long.”

The approval of maralixibat was based on the results of the pivotal ICONIC study, as well as 5 years of data from supportive studies.

ICONIC was a randomized, controlled long-term phase 2B study. The primary results at week 48 showed that maralixibat demonstrated significant reductions in serum bile acids, pruritus, and xanthomas.

There were a total of 31 children (mean age, 5.4 years) enrolled in the ICONIC study. First, patients were treated for 18 weeks with maralixibat before being randomized to receive either placebo (n = 16) or maralixibat (n = 13) for 4 weeks. After this randomized withdrawal period, all patients were treated with maralixibat for the remainder of the 48 weeks.

Treatment-emergent adverse events (TEAEs) were reported in 30 of the patients. Only 4 patients had serious TEAEs, which were considered to be unrelated to maralixibat, and 2 TEAEs leading to discontinuation, which were also unrelated to the therapy. Diarrhea and abdominal pain were the most frequent TEAEs.

“Until now, patients have had limited-to-no treatment options to address the severe and unrelenting itch that significantly impacts both patients and their families,” said Roberta Smith, president, Alagille Syndrome Alliance, and an ALGS mom.

Mirum has submitted an application for maralixibat with the European Medicines Agency.

“The six-year event-free survival data, coupled with the previously presented ICONIC data, provides a catalyst to accelerate our ALGS submission,” said Chris Peetz, president and CEO of Mirum. “We feel a tremendous urgency to advance maralixibat for patients as quickly as possible as its availability may provide a significant shift in treatment options for patients living with this unrelenting rare liver disease.”