Former Shire asset becomes Mirum’s first FDA-approved rare disease drug


A Mirum Pharmaceuticals drug that treats the severe itching caused by Alagille syndrome is now FDA approved, making it the first authorized therapy for the thousands of children who have the rare liver disease and the first product for the biotech company.

The drug, a grape-flavored solution called maralixibat, is approved for children age 1 and older. Foster City, California-based Mirum will market its new product under the name “Livmarli.”

Alagille syndrome is an inherited disorder that causes abnormalities in the bile ducts, which in turn leads to the accumulation of bile in the liver. This complication, called cholestasis, leads to scarring and damage of the organ. It also causes severe itching called cholestatic pruritus. Prior to Livmarli, the only treatments for this itching were medications used off label. In severe cases, progressive worsening of the liver damage and itching requires patients to undergo a liver transplant.

Livmarli is an ileal bile acid transporter inhibitor, which is a jargony way of saying that it decreases the absorption of bile acids from a part of the small intestine. The FDA decision is based on the results of a placebo-controlled Phase 2b study that enrolled 31 patients who received treatment for 52 weeks. Mirum reported that treatment with its drug led to clinically and statistically significant differences in pruritus as scored according to an itching scale. The company said the reduction in itching was maintained through four years. In clinical trials, the most commonly reported adverse reactions included diarrhea, abdominal pain, and vomiting.

Mirum estimates that between 2,000 and 2,500 pediatric patients in the U.S. are eligible for treatment with Livmarli, Chief Operating Officer Peter Radovich said during a conference call Wednesday. The drug, which comes in a bottle and requires no refrigeration, is dosed according to a patient’s weight. The wholesale price, before any rebates or discounts, is $1,550 per milliliter, Radovich said. Based on the average 17 kilogram weight (about 37.4 pounds) of patients in clinical trials, Mirum estimates the annual gross cost of the drug will be $391,000. Radovich said that the price is comparable to other products addressing similarly sized patient populations for diseases of similar severity.

Mirum isn’t the only company addressing pruritus with a drug designed to decrease absorption of bile acids. Like Livmarli, Albireo Pharma drug Bylvay is an ileal bile acid transporter inhibitor. In July, the Boston company won FDA approval for its capsule as a treatment for progressive familial intrahepatic cholestasis (PFIC), a different rare liver disease.

Mirum is also pursuing PFIC, but for a different genetic mutation than the one addressed in the Albireo drug approval. The European Medicines Agency has accepted Mirum’s marketing authorization application in PFIC. A Phase 3 study is also underway evaluating higher doses of the drug in a broader range of PFIC patients. The company expects preliminary data will be ready early next year. A Phase 2 study is underway testing the drug in biliary atresia (BA).

Mirum licensed Livmarli from Shire, which is now a part of Takeda Pharmaceutical. The 2018 licensing agreement makes Mirum responsible for up to $107 million in milestone payments tied to the clinical and regulatory progress of the drug in Alagille syndrome, PFIC, and BA.

With the FDA approval of Livmarli in Alagille syndrome, Mirum was awarded a rare disease pediatric priority review voucher. The company may apply that voucher toward speedier FDA review of one of its other products. Alternatively, the company may choose to sell it. Biopharmaceutical companies have paid $100 million or more for such vouchers.

Photo: Sakramir, Getty Images