RARE Daily

Mirum Initiates Rolling Submission of NDA for ALGS Treatment and Launches Expanded Access Program

September 2, 2020

Rare Daily Staff

Mirum Pharmaceuticals said it has submitted the first portion of its rolling New Drug Application to the U.S. Food and Drug Administration for maralixibat for the treatment of cholestatic pruritus in patients with Alagille syndrome.

At the same time, Mirum launched an expanded access program to provide access to maralixibat for eligible patients with Alagille syndrome (ALGS), who are not part of an ongoing clinical trial, prior to it potential approval and until it is available by prescription.

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. The drug 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.

“We believe the results of our clinical program demonstrate the potential of maralixibat to transform the treatment of this life-threatening disease,” said Chris Peetz, president and CEO at Mirum. “We are also pleased to launch our Expanded Access Program for patients with ALGS in the United States and Canada and are evaluating ways in which we can make maralixibat available for patients with ALGS in other countries. Additionally, we are planning to broaden access to maralixibat through our anticipated Marketing Authorization Application submission for patients with PFIC2 in Europe later this year.”

Mirum expects to complete the NDA submission in the first quarter of 2021. If approved, it would be the first treatment available for use in Alagille syndrome. The company is planning for a potential launch of maralixibat in ALGS in the second half of 2021.

Mirum’s Expanded Access Program (EAP) for maralixibat for the treatment of cholestatic pruritus in patients with ALGS one year of age and older is open for registration in the United States and Canada. Through this program, physicians can request access to maralixibat for eligible patients who are not part of an ongoing clinical trial.

The EAP, sometimes referred to as “compassionate use,” provides a potential pathway for a patient with an immediately life-threatening condition or serious disease to gain access to an investigational medicine for the treatment of that disease outside of a clinical trial when no comparable or satisfactory alternative therapy options are available.

Maralixibat was previously granted Rare Pediatric Disease designation for ALGS and, as such, may qualify for receipt of a priority review voucher if it is approved by the FDA. Maralixibat was also granted Breakthrough Therapy designation for the treatment of pruritus associated with ALGS in patients one year of age and older. Maralixibat was granted Orphan Drug Designation by the FDA for the treatment of patients with PFIC and ALGS in the United States.

Photo: Chris Peetz, president and CEO at Mirum



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