According to GuruFocus, the European Medicines Agency (EMA) recently validated a Marketing Authorization Application (MAA) submitted by biopharmaceutical company Mirum Pharmaceuticals, Inc. (“Mirum”). The MAA was centered around maralixibat, an investigational therapy for progressive familial intrahepatic cholestasis type 2 (PFIC2). Because the MAA has been validated, the EMA will now review the application for potential approval.
Maralixibat
Developed by Mirum, maralixibat fits right into the company’s pipeline of treatments for patients with rare or serious liver diseases. This novel treatment, administered orally, inhibits the apical sodium-dependent bile acid transporter (ASBT). As a result, excess bile acids are removed from the body via feces. When lower levels of bile acids exist throughout the system, it reduces the potential for liver damage related to bile acids. Thus far, over 1,600 patients have taken maralixibat.
Data from various studies shows the efficacy of maralixibat. In the Phase 2b ALGS study, researchers determined that maralixibat reduced pruritus (intense itching), xanthomas, and bile acids. Similar benefits were discovered in the Phase 2 INDIGO clinical trial for pediatric patients with PFIC2; in addition to reducing pruritus and improving growth, the drug also improved 5-year transplant-free survival. While the drug is relatively well-tolerated, some side effects did occur, including diarrhea and abdominal pain and discomfort. Currently, the drug received Breakthrough Therapy designation within the United States.
A Phase 3 clinical trial on maralixibat for PFIC2 will share available data in the later half of 2021. Finally, outside of the MAA, Mirum also submitted a New Drug Application (NDA) to American regulatory authorities.
Progressive Familial Intrahepatic Cholestasis (PFIC)
Altogether, progressive familial intrahepatic cholestasis is a group of rare liver conditions caused by biliary epithelial transporter defects. Normally, these transporters help regulate and transport bile. However, these defects prevent this through cholestasis (obstructing bile), causing a host of physical issues. PFIC is inherited. There are a number of subsets; for example, maralixibat was recently approved for PFIC2, or bile salt export pump deficiency. ABCB11 gene mutations cause PFIC2, which makes up nearly 50% of all PFIC cases. Typically, PFIC impacts children, with symptom onset before 2 years old.
Symptoms include:
- Jaundice (yellowing of the skin and eyes)
- Pruritus
- Cirrhosis
- Fatigue
- Liver enlargement
- Diarrhea
- Failure to thrive
- Vision and balance problems
- Suicidal ideation