FDA expands maralixibat label to include PFIC patients aged 12 months and older

FDA expands maralixibat label to include PFIC patients aged 12 months and older | Image Credit: © Calin - © Calin - stock.adobe.com.

Maralixibat (LIVMARLI; Mirum Pharmaceuticals), originally approved by the FDA to treat cholestatic pruritus in patients with progressive familial intrahepatic cholestasis (PFIC) aged 5 years and older, is now eligible to treat patients aged 12 months and older following the approval of an expanded indication.^1,2

According to a press release from Mirum, the expanded label also includes the higher concentration formulation of maralixibat that was evaluated in a clinical study.¹

Initial approval of maralixibat, an orally-administered, once-daily, ileal bile acid transporter (IBAT) inhibitor, was based on data from the phase 3 MARCH PFIC study(NCT03905330) of maralixibat that featured 93 patients across a range of genetic PFIC subtypes (PFIC1, PFIC2, PFIC3, PFIC4, PFIC6 and unidentified mutational status).^2,3

Patients treated with maralixibat had statistically significant improvements in pruritus (P < .0001), serum bile acids (P < .0001), bilirubin (P < .0471), and growth measured by weight z-score (P = .0391).²

"Maralixibat approval for infants with PFIC... [will] offer a potential treatment for pruritus in those who may not have responded adequately to other medications including antihistamines, cholestyramine, and rifampin," said Paula Hertel, MD, staff physician, Texas Children's Hospital; assistant professor, Pediatrics, Baylor College of Medicine, in a previous statement to Contemporary Pediatrics. "Itch can make children completely miserable, including during infancy, significantly impairing quality of life for patients and their parents."²

"We can reduce levels of circulating bile acids by impairing their reabsorption in the small intestine, and this has been shown to alleviate pruritus," Hertel said of the initial approval that came on March 13, 2024. "Biliary diversion surgery is one way to divert bile acids away from the ileum, preventing their reabsorption and lowering levels in the serum. This procedure is a well-established and effective treatment for pruritus in some types of PFIC. [Apical sodium-dependent bile acid transporters] (ASBT) inhibitors such as maralixibat medically accomplish the same goal, by impairing bile acid reabsorption in the small bowel and reducing serum bile acid levels and itch."²

According to Mirum, maralixibat is not for use in PFIC type 2 patients who have a severe defect in the bile salt export pump protein.¹

“The launch of LIVMARLI in PFIC is going well and we are thrilled that it will now be available for patients 12 months and older,” said Chris Peetz, CEO, Mirum, in a press release. "PFIC is generally diagnosed when children are young, and initiating treatment quickly after diagnosis will help to ensure they have fewer days suffering from pruritus associated with this rare liver disease.”¹

References:

1. Mirum's LIVMARLI now approved for PFIC in patients 12 months and older. Mirum Pharmaceuticals. Press release. July 25, 2024. Accessed July 25, 2024. https://ir.mirumpharma.com/news-events/News/news-details/2024/Mirums-LIVMARLI-Now-Approved-for-PFIC-in-Patients-12-Months-and-Older/default.aspx
2. Fitch, J. FDA approves maralixibat to treat cholestatic pruritus in PFIC patients 5 years and up. Contemporary Pediatrics. March 13, 2024. Accessed July 25, 2024. https://www.contemporarypediatrics.com/view/fda-approves-maralixibat-to-treat-cholestatic-pruritus-in-pfic-patients-2-months-and-up
3. Miethke AG, Moukarzel A, Porta G, et al. Maralixibat in progressive familial intrahepatic cholestasis (MARCH-PFIC): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2024 Jul;9(7):620-631. doi: 10.1016/S2468-1253(24)00080-3. Epub 2024 May 6. Erratum in: Lancet Gastroenterol Hepatol. 2024 Jul;9(7):e10. doi: 10.1016/S2468-1253(24)00169-9. PMID: 38723644.