Livmarli now approved in US for PFIC patients 1 year and older
Label expansion also includes higher concentration formula
The U.S. Food and Drug Administration (FDA) has approved a label expansion for Livmarli (maralixibat) that allows the medication to be used in patients with progressive familial intrahepatic cholestasis (PFIC) as young as 1 year.
The liquid oral therapy from Mirum Pharmaceuticals was first approved for PFIC in March, but only for patients 5 years and older. That was because younger patients in clinical testing had received a higher concentration formulation of Livmarli than the one already on the therapy’s label, so Mirum had to apply separately for that clearance. Now, the label expansion includes this higher concentration formula as well as the expanded age range.
Livmarli was also recently approved for PFIC patients 3 months and older in the European Union.
Clinical trial data show Livmarli can ease symptoms of PFIC
These decisions are all supported by clinical trial data that show the therapy can ease the symptoms of PFIC, including severe itch, or pruritus.
“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, Mirum’s CEO, said in a company 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.”
PFIC encompasses a group of rare genetic diseases that lead to impairments in the production or secretion of the digestive fluid bile in the liver. These impairments cause cholestasis, or stalled bile flow. Among the wide range of cholestasis symptoms is pruritus, which occurs when bile acids start to back up into the bloodstream.
Livmarli works by blocking the action of the ileal bile acid transporter, a protein that helps recycle bile acids in the intestines back to the liver. In doing so, it helps promote bile clearance through the intestines, thereby lowering bile levels in the bloodstream and easing pruritus.
Before its approvals for PFIC, Livmarli was first approved in the U.S. and European Union for pruritus in Alagille syndrome, another rare liver disease characterized by cholestasis.
Data supporting the therapy’s initial approval for PFIC, and its recent label expansion, came from the Phase 3 MARCH-PFIC (NCT03905330) clinical trial, which enrolled 93 children and adolescents, ages 1-17, with various genetic subtypes of PFIC. Participants were randomly assigned to receive Livmarli or a placebo for about six months.
Younger patients in the trial received the higher concentration formulation of Livmarli that was also approved in the recent label expansion.
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.
Livmarli found to ease pruritus and reduce blood bile acid levels
Results showed Livmarli eased pruritus and lowered blood bile acid levels relative to the placebo across PFIC types, and was generally safe and well tolerated. The most commonly reported side effect was diarrhea, which was usually temporary and mild.
Participants who completed MARCH-PFIC could then enroll in MARCH-ON (NCT04185363), an ongoing extension study in which all patients are receiving Livmarli for up to two years. Data from MARCH-ON have so far indicated that benefits observed in the main trial have been sustained with long-term treatment.
As noted on its label, while Livmarli is approved for all PFIC types, it is not recommended for patients with PFIC type 2 who carry certain mutations. The label also comes with a warning that children younger than 5 years could be at risk of toxicity from exposure to propylene glycol, one of the therapy’s inactive ingredients, and should be monitored.
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