Rare Daily Staff

The U.S. Food and Drug Administration granted Mirum Pharmaceuticals Breakthrough Therapy designation for maralixibat, its experimental therapy for the treatment of pruritus associated with Alagille syndrome in patients 1 year of age and older.

Breakthrough Therapy Designation is granted by the FDA to investigational medicines intended to treat a serious or life-threatening condition for which preliminary clinical evidence may demonstrate substantial improvement on at least one clinically significant endpoint over available therapy. It is intended to expedite development and review.

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.

Maralixibat is a novel, minimally-absorbed, 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.

The Breakthrough Therapy designation of maralixibat was granted based on evidence from the ICONIC Phase 2b clinical trial in children with ALGS. Results from the clinical trial were recently presented at the International Liver Congress.

X