FDA Approves Label Expansion for Maralixibat (Livmarli) in PFIC

Credit: US Food and Drug Administration

The US Food and Drug Administration has approved a label expansion for Mirum Pharmaceuticals’ maralixibat (Livmarli) oral solution for the treatment of cholestatic pruritus in patients with progressive familial intrahepatic cholestasis (PFIC).¹

Announced on July 25, 2024, the expanded label includes use in patients with PFIC 12 months of age and older as well as the higher concentration formulation of maralixibat evaluated in the phase 3 MARCH study.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,” Chris Peetz, chief executive officer at Mirum, said in a press release.¹ “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.”

An orally administered, once-daily ileal bile acid transporter (IBAT) inhibitor, maralixibat is the only FDA-approved medication for the treatment of cholestatic pruritus in patients with Alagille syndrome ≥ 3 months of age. It is also being evaluated in late-stage clinical studies in other rare cholestatic liver diseases including biliary atresia and has received Breakthrough Therapy designation for Alagille syndrome and PFIC type 2 as well as orphan designation for Alagille syndrome and PFIC.²

Maralixibat earned its second rare liver disease indication earlier this year with its approval for the treatment of cholestatic pruritus in patients 5 years or older with PFIC. The decision was supported by data from the phase 3 MARCH-PFIC study, the largest randomized trial conducted in PFIC. Among a cohort of 93 patients with a range of genetic PFIC subtypes, patients treated with maralixibat had statistically significant improvements in pruritus (P <.0001), serum bile acids (P <.0001), bilirubin (P = .0471), and growth as measured by weight z-score (P = .0391).²

Full phase 3 MARCH-PFIC data were published in The Lancet 2 months after this approval and provided further insight into the effects of treatment with maralixibat in patients with PFIC, demonstrating its positive impact on pruritus and predictors of native liver survival. Conducted at 29 sites in 16 countries across Europe, Asia, and North and South America, the trial is billed as providing the largest and most comprehensive dataset for an IBAT inhibitor in PFIC.³

The primary outcome of interest was mean change in average morning ItchRO(Obs) severity score between baseline and weeks 15–26 among those with biallelic, non-truncated BSEP deficiency without low or fluctuating serum bile acids or previous biliary surgery. The secondary efficacy outcome of interest was the mean change in total serum bile acids between baseline and the average of weeks 18, 22, and 26 in the BSEP cohort.³

Results indicated the study met both the primary and secondary efficacy endpoints, with use of maralixibat associated with statistically significant and clinically meaningful improvements observed with use by week 2 and sustained throughout the duration of the 26-week study. Further analysis of data from the trial indicated use was associated with improvements in bilirubin concentrations, growth, and sleep disturbances relative to placebo. Additionally, safety analyses suggested there were no new safety signals during the trial, with the most common adverse event being diarrhea and most of these events considered to be mild and transient in nature.³

References

1. ^{Mirum Pharmaceuticals. Mirum’s LIVMARLI Now Approved for PFIC in Patients 12 Months and Older. 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. ^{Brooks, A. FDA Approval of Maralixibat for Cholestatic Pruritus in PFIC Signals New Frontier for IBAT Inhibitor. HCPLive. March 13, 2024. Accessed July 25, 2024. https://www.hcplive.com/view/fda-approval-of-maralixibat-for-pfic-ibat-inhibitors}
3. ^{Campbell, P. Full MARCH-PFIC Data Offers Further Insight into Maralixibat in PFIC. HCPLive. May 7, 2024. Accessed July 25, 2024. https://www.hcplive.com/view/full-march-pfic-data-offers-further-insight-into-maralixibat-in-pfi}