Policy & Regulation
European Medicines Agency Validates Marketing Authorization Application for Maralixibat in Patients with PFIC2
30 November 2020 - - US-based biopharmaceutical company Mirum Pharmaceuticals, Inc's (NASDAQ: MIRM) Marketing Authorization Application for its investigational medicine, maralixibat, for the treatment of patients with progressive familial intrahepatic cholestasis type 2 (PFIC2), also known as bile salt export pump deficiency, was accepted for review (validated) by the European Medicines Agency, the company said.

The validation of the application by the EMA confirms all essential regulatory elements are included in the submission such that the EMA can begin its review.

Data from the Phase 2 INDIGO study evaluating maralixibat for pediatric patients with PFIC2 served as the basis of the MAA submission.

Mirum recently announced data showing five-year transplant-free survival for patients who achieved serum bile acid control.

The data also demonstrated improvements across multiple parameters including pruritus control, improvements of liver enzyme and bilirubin levels, and improvement in growth.

These data were presented at the annual meeting of the European Association for the Study of the Liver. The MAA submission also includes data on five-year event-free survival with maralixibat compared to the NAPPED natural history cohort.

To provide further evidence of maralixibat's potential in PFIC2 with higher doses and other PFIC subtypes, Mirum is conducting a Phase 3 study, MARCH, with completion of enrollment expected in 2Q21.

In addition to the MAA submission for maralixibat in PFIC2, Mirum has also initiated a rolling new drug application to the US Food and Drug Administration for maralixibat for the treatment of cholestatic pruritus in patients with Alagille syndrome.

Mirum expects to complete the submission in the first quarter of 2021, with a planned launch in the second half of the same year.

The company also recently launched an Expanded Access Program making maralixibat available to eligible patients with ALGS in the United States, Canada, Australia, and certain countries in Europe.

Maralixibat is a novel, minimally absorbed, orally administered investigational drug being evaluated in several cholestatic liver diseases.

Maralixibat inhibits the apical sodium-dependent bile acid transporter, resulting 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.

More than 1,600 individuals have received maralixibat, including more than 120 children who have received maralixibat as an investigational treatment for Alagille syndrome and progressive familial intrahepatic cholestasis.

In the ICONIC Phase 2b ALGS clinical trial, patients taking maralixibat had significant reductions in bile acids and pruritus compared to placebo, as well as reduction in xanthomas and accelerated growth long-term.

In a Phase 2 PFIC study, a genetically defined subset of BSEP deficient (PFIC2), patients responded to maralixibat.

The US Food and Drug Administration has granted maralixibat Breakthrough Therapy designation for treatment of pruritus associated with ALGS in patients one year of age and older and for PFIC2.

Maralixibat was generally well-tolerated throughout the studies, the company said. The most frequent treatment-related adverse events were diarrhea and abdominal pain.

Until maralixibat is approved by regulatory authorities and available for prescribing, the medication is available to patients with ALGS through Mirum's expanded access program.