In a recent news release on Morningstar, biopharmaceutical company Albireo Pharma, Inc. (“Albireo”) shared that its investigational drug candidate Bylvay (odevixibat) earned a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP). The positive CHMP opinion centers around data from the Phase 3 PEDFIC 1 and PEDFIC 2 clinical trials, which evaluated Bylvay for patients with progressive familial intrahepatic cholestasis (PFIC).

Bylvay

According to the European Medicines Agency (EMA), Bylvay will:

be available as 200 mg, 400 mg, 600 mg and 1200 mg hard capsules. The active substance of Bylvay is odevixibat, a reversible, potent, selective inhibitor of the ileal bile acid transporter (IBAT) that acts locally in the distal ileum, reducing the reuptake of bile acids and increasing the clearance of bile acids through the colon.

The treatment, taken 1x daily, could offer patients a more effective and less invasive therapeutic option. Typically, patients with PFIC require some sort of surgical intervention, such as liver transplants. Thus, Bylvay, by reducing bile acids, improving symptoms, and helping with growth, could fill an unmet need within this patient population. Additionally, Albireo intends for Bylvay to be a treatment option for patients with all forms of PFIC (1, 2, and 3).

Although Bylvay is not yet approved within Europe, it is being explored on an accelerated approval pathway. The decision on the marketing authorization application (MAA), and the intended product launch, should be available before the end of 2021. The positive CHMP approval marks the move towards the MAA granting.

Outside of PFIC, Albireo is also considering Bylvay as a potential treatment for patients with Alagille syndrome and biliary atresia. In fact, the treatment received Orphan Drug designation for all of these indications.

PEDFIC 1 and PEDFIC 2

In part, the positive CHMP opinion hinged on data from both Phase 3 clinical trials listed above. Some findings from the trials included:

• Bylvay was relatively safe and well-tolerated. During the trials, there were no serious adverse reactions. While some side effects did occur, these were relatively mild, with diarrhea and frequent bowel movements being the most common.
• In the PEDFIC 1 clinical trial, Bylvay met the primary endpoints. During the trial, the treatment reduced patients’ pruritus (intense itching) and serum bile acid levels.
• Ultimately, Bylvay helped reduce serum bile acid levels and pruritus, and improve growth, for a sustained period of time (48+ weeks).

Progressive Familial Intrahepatic Cholestasis (PFIC)

Progressive familial intrahepatic cholestasis (PFIC) refers to a class of rare liver conditions that generally present in infancy. ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, MYO5B, and USP53 gene mutations have all been linked to PFIC. These cause defects within the biliary epithelial transporters. Normally, these cells help regulate bile transportation out of the liver. But these gene mutations cause protein deficiencies, leading bile to build up within the liver. There are three main forms of PFIC: 1, 2, and 3. While the former two usually develop in infancy (before 2 years old), PFIC 3 may not appear until adolescence. PFIC causes progressive liver damage and cirrhosis, with many patients experience liver failure before age 10. Treatment is usually necessary to assist with overall survival.

Symptoms include:

• Cholestasis (bile obstruction)
• Failure to thrive
• Easy bruising and bleeding
• Dark urine and pale stool
• Pruritus (intense and sometimes debilitating itching)
• Jaundice (yellowing of the skin and eyes)
• Vitamin deficiencies
• Deafness
• Poor balance
• More frequently or easily broken bones
• Pancreatitis
• Vision and auditory problems
• Suicidal ideation (in those who present symptoms in adolescence)
• Increased risk of developing hepatocellular carcinoma