Rolling NDA Completed: Maralixibat for Alagille Syndrome

In a recent press release, biopharmaceutical company Mirum Pharmaceuticals, Inc. (“Mirum”) shared that the company finished its rolling New Drug Application (NDA) submission. The NDA focuses around maralixibat, an investigational therapy for cholestatic pruritus (intense itching caused by liver disease or damage) in patients with Alagille syndrome. Currently, there are no approved treatments for Alagille syndrome. Thus, if the NDA is accepted, it would meet a huge unmet need for patients.


Developed by Mirum, maralixibat is an investigational treatment designed for a variety of cholestatic liver disease. Medscape describes cholestasis as:

a decrease or arrest in the flow of bile.

So cholestatic liver diseases are those characterized by issues with the bile ducts or the flow of bile. The drug, taken orally, acts as an ASBT inhibitor. As a result, bile acids are increasingly removed from the body via stool, lowering bile acid levels throughout the body. Maralixibat is designed for patients ages 1+.

The NDA is supported by data from the Phase 2b ICONIC clinical trial, as well as data sourced from additional studies. Within the ICONIC trial, researchers found that maralixibat helped reduce bile acids, itching, and xanthomas, skin lesions containing fat and cholesterol. Additionally, maralixibat also spurred patient growth. While it was fairly well-tolerated, some side effects included abdominal pain and diarrhea.

Maralixibat received Breakthrough Therapy, Orphan Drug, and Rare Pediatric Disease designations. Although it is currently not available for use as a prescription drug, maralixibat is available through the Expanded Access Program. However, pending FDA approval, Mirum hopes to be able to provide maralixibat to patients on a wider scale by the end of 2021.

Alagille Syndrome

NOTCH2 and JAG1 gene mutations cause Alagille syndrome, a rare multi-system disorder. Patients with Alagille syndrome typically have narrow, malformed, or deficient bile ducts, causing bile to build up in the liver. Up to 75% of patients require a liver transplant before adulthood. Symptoms typically appear within the first three months of life. These include:

  • Heart abnormalities and congenital heart defects
  • Liver disease
  • Pale, loose stools
  • Intense itching
  • Failure to thrive
  • Jaundice (yellowing of the skin and eyes)
  • Cholestasis
  • Deeply-set and widely spaced eyes
  • Xanthomas
  • Dark urine
  • Enlarged liver and spleen

Learn more about Alagille syndrome.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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