Rare Daily Staff

The U.S. Food and Drug Administration has granted Mirum Pharmaceuticals the Rare Pediatric Disease designation for maralixibat for the treatment of pruritus associated with the rare liver condition Alagille syndrome.

Alagille syndrome (ALGS) is a rare genetic disorder in which bile ducts are abnormally narrow, malformed, and reduced in number, which leads to bile accumulation in the liver and ultimately progressive liver disease. In patients with ALGS, multiple organ systems may be affected by the mutation, including the liver, heart, kidneys and central nervous system. The accumulation of bile acids prevents the liver from working properly to eliminate waste from the bloodstream and leads to progressive liver disease that may require liver transplantation. The severe itching, known as pruritus, that is experienced by patients with ALGS is among the most severe in any chronic liver disease and is present in most affected children by the third year of life. The estimated incidence of ALGS is one in every 30,000 to 50,000 births in the United States and Europe.

Maralixibat is an orally-administered, experimental drug being evaluated in several rare cholestatic liver diseases for pediatric populations. Maralixibat inhibits the apical sodium dependent bile acid transporter, which results in more bile acids being excreted in the feces, leading to lower levels of bile acids systemically, thereby potentially reducing bile acid mediated liver damage and related effects and complications.

In early November, Mirum said that results from the long-term extension of the phase 2b ICONIC study demonstrated the durability of treatment effect and disease-modifying potential of maralixibat in children with Alagille syndrome with reductions in serum bile acids and pruritus statistically significant in the participants who remained on maralixibat through 191 weeks of treatment compared to baseline.

The FDA grants Rare Pediatric Disease designation for serious or life-threatening diseases with manifestations in individuals aged from birth to 18 years, including access to the FDA’s expedited review and approval process. The designation makes maralixibat eligible for a Rare Pediatric Disease Priority Review voucher upon approval of the therapy by the FDA.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Swedish Orphan Biovitrum sold its Priority Review voucher to AstraZeneca for $95 million.

Maralixibat was also recently granted Breakthrough Therapy designation by the FDA for Alagille syndrome.

The company plans to pursue full approval for the indication of pruritus associated with Alagille syndrome based on feedback from its meeting with the FDA and the results from the ICONIC study of maralixibat in children with Alagille syndrome. It is planning a rolling NDA submission, which will be initiated in the third quarter of 2020.

“We look forward to working with the FDA to bring this much-needed treatment option to children living with Alagille syndrome as rapidly as possible,” said Chris Peetz, president and CEO of Mirum. “As part of our commitment to patients and their families we also plan to initiate an expanded access program in the second half of 2020,” said Chris Peetz, president and CEO of Mirum.

Photo: Chris Peetz, president and CEO of Mirum

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