FDA Approves Livmarli for Second Liver Disease Indication

The FDA has approved an additional indication for Livmarli (maralixibat) oral solution: to treat cholestatic pruritus (itch) in patients 5 years of age and older with progressive familial intrahepatic cholestasis (PFIC).

Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic disorder that causes progressive liver disease. In people with PFIC, liver cells are less able to secrete bile. The disease is estimated to affect 1 in every 50,000 to 100,000 births in the United States and Europe.

“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,” Emily Ventura, executive director of the PFIC Network and mom to a daughter with PFIC, said in a press release.

Developed by Mirum Pharmaceuticals, Livmarli was approved by the FDA in 2021 to treat cholestatic pruritus in Alagille syndrome (ALGS) in children 1 year of age and older. In March 2023, the indication was expanded to include infants three months and older.

The cost for Livmarli oral solution (9.5 mg/mL) is about $56,240 for a supply of 30 milliliters, according to Drugs.com. Eligible patients with commercial insurance may pay as little as $10 out of pocket per prescription. About 94% of patients are approved by their insurance and 98% of patients pay $10 or less per fill. In 2023, Livmarli generated global net sales of $141.8 million, an 89% growth over 2022 net sales.

The approval for children with PFIC is based on data from the phase 3 MARCH study, which enrolled 93 patients across a range of genetic PFIC types, including PFIC1, PFIC2, PFIC3, PFIC4, PFIC6, and unidentified mutational status. In the MARCH study, Livmarli-treated patients had statistically significant improvements in itch, serum bile acids, bilirubin, and growth as measured by weight z-score. The sNDA also includes data from the phase 2 INDIGO study of PFIC2 patients demonstrating transplant-free survival in all serum bile acid responders after more than five years of treatment with Livmarli.

The extension study, MARCH-ON evaluated patients who had received Livmarli for 26 weeks and followed them for two years, as well patients who had received placebo and then switched to Livarli. These patients were followed for one year. In patients who received Livmarli and were followed for two years, improvements in pruritus severity, serum bile acid (sBA) levels, total bilirubin, and growth were seen.

The placebo-Livmarli group demonstrated rapid (as early as three weeks) and significant improvements in pruritus severity and serum bile acid levels similar to those observed in the original MARCH Livmarli group. he most common treatment emergent adverse events were GI, occurred early in treatment, and were mild and transient in nature.

Data from the long-term extension study were presented at The Liver Meeting, the American Association for the Study of Liver Diseases (AASLD) annual meeting in Boston in November 2023.

Mirum has also submitted an additional supplemental new drug application (sNDA) to introduce a higher concentration formulation of Livmarli, which was used during the MARCH study, to enable label expansion for younger patients with PFIC, later this year