FDA Approves Mirum’s Livmarli to Treat Cholestatic Pruritus in Patients with Alagille Syndrome
September 30, 2021
The U.S. Food and Drug Administration approved Mirum Pharmaceuticals’ Livmarli oral solution for the treatment of cholestatic pruritus in patients with Alagille syndrome one year of age and older.
Livmarli, a minimally absorbed ileal bile acid transporter (IBAT) inhibitor, is the first and only FDA-approved medication in this rare liver disease which affects 2,000 to 2,500 children in the United States.
Alagille syndrome (ALGS) is a rare genetic disorder caused by abnormalities in bile ducts that can lead to progressive liver disease. Malformed or reduced bile ducts cause cholestasis, the accumulation of bile acids in the liver, which leads to inflammation and liver injury, and prevents the liver from working properly. Cholestasis in ALGS is associated with pruritus which is among the most common indications for liver transplant in ALGS, which according to recent reports, 60 percent to 75 percent of patients with ALGS will need before reaching adulthood.
“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,” said Binita Kamath, pediatric hepatologist at The Hospital for Sick Children in Toronto, Ontario, Canada. “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 Livmarli 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 is based on the pivotal ICONIC study as well as five years of data from supportive studies resulting in a robust body of evidence in 86 patients with ALGS. Data from ICONIC demonstrated statistically significant reductions in pruritus, one of the most common and arduous symptoms associated with the disease, which was maintained through four years.
“Today is a great day for the Alagille syndrome community with the approval of a much-needed new treatment option to address one of the most debilitating effects of this disease,” said Chris Peetz, president and CEO of Mirum.
Serious side effects include changes in liver tests that may be a sign of liver injury, stomach and gastrointestinal problems, and a condition called Fat Soluble Vitamin (FSV) Deficiency caused by low levels of certain vitamins (vitamin A, D, E, and K) stored in body fat. FSV deficiency is common in patients with Alagille syndrome but may worsen during treatment. Other common side effects reported during treatment were bone fractures and gastrointestinal bleeding.
Livmarli is now available for prescribing. In conjunction with the approval, Mirum received a rare pediatric disease priority review voucher.
Mirum is currently evaluating Livmarli (maralixibat) in late-stage clinical studies in other rare cholestatic liver diseases including progressive familial intrahepatic cholestasis and biliary atresia, of which both have received Breakthrough Therapy designation and Orphan Drug designation.
Mirum has submitted a Marketing Authorization Application to the European Medicines Agency for maralixibat for the treatment of cholestatic liver disease in patients with Alagille syndrome.
Photo: Binita Kamath, pediatric hepatologist at The Hospital for Sick Children in Toronto, Ontario, Canada
Author: Rare Daily Staff
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