Bylvay™ (odevixibat) is the first drug indicated for the treatment of pruritus in patients aged three months and older with progressive familial intrahepatic cholestasis (PFIC).
Developed by US-based biopharmaceutical company Albireo Pharma, Bylvay is available as 200mcg and 600mcg oral pellets, as well as capsules of 400mcg and 1200mcg dosage strengths.
Regulatory approvals of Bylvay
In December 2020, Albireo Pharma submitted a new drug application (NDA) to the US Food and Drug Administration (FDA) and a marketing authorisation application (MAA) to the European Medicines Agency (EMA) seeking approval of odevixibat for the treatment of patients with PFIC.
The US FDA accepted the NDA for priority review in January 2021, while the EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended the drug for approval in May 2021.
Odevixibat secured approval for the condition from the FDA and EMA in July 2021. In Europe, odevixibat was approved for patients aged six months and older with PFIC and its commercial launch in the European Union, beginning with Germany, is expected in September 2021. In addition, the FDA has issued a rare paediatric disease priority review voucher to the company.
The odevixibat also holds orphan drug designations for the treatment of Alagille Syndrome, biliary atresia and primary biliary cholangitis.
Causes and symptoms of PFIC
PFIC is a rare, progressive, life-threatening liver disorder affecting young children. It is a hereditary disease in which the liver cells cannot produce and secrete bile properly, resulting in the build-up of bile in the liver cells called cholestasis.
Cholestasis can damage the liver, causing cirrhosis and liver failure within the first ten years of life. There are three known types of PFIC, namely PFIC type 1, PFIC type 2 and PFIC type 3.
The most prominent feature of the disorder is severe and debilitating pruritus or intense itching. Other symptoms include jaundice, poor weight gain and slowed growth.
PFIC affects roughly one to two children for every 100,000 live births. Both sexes are equally affected by the disease.
Bylvay mechanism of action
Bylvay is a once-daily, non-systemic, reversible inhibitor of ileal bile acid transporter (IBAT), which decreases the reuptake of bile salts from the terminal ileum into the hepatic portal circulation. The therapy acts locally in the small intestine.
The elimination of bile acids from the enterohepatic circulation reduces bile acid levels in serum and the liver.
Clinical trials on Bylvay
The FDA’s approval of Bylvay was supported by the PEDFIC I and PEDFIC II clinical trials. They were the largest, global, Phase III clinical trials ever performed in the PFIC space.
PEDFIC I was a 24-week, randomised, double-blind, placebo-controlled trial enrolling 62 paediatric patients aged between six months and 17 years of age with PFIC type 1 or type 2 and severe itching.
The patients were randomised to receive either placebo, 40mcg/kg odevixibat or 120mcg/kg odevixibat.
The study’s primary endpoints were the difference in patient’s scratching as observed by their caregiver twice a day and assessed on a five-point ordinal scale, as well as serum bile acid responses.
Results showed that patients treated with odevixibat achieved a significant decline in itching or scratching and reduced serum bile acid responses. Around 53.5% of patients in the odevixibat arms showed a significant reduction in pruritus, compared to 28.7% in the placebo arm.
Odevixibat’s safety was assessed in PEDFIC II, a 72-week, long-term, open-label, single-arm extension study. The study enrolled 79 participants with PFIC type 1, 2 and 3 aged between four months and 25 years of age. The patients received 120mcg/kg of the drug once a day.
PEDFIC II confirmed that Bylvay showed sustained reductions in serum bile acids and improvements in pruritus, growth and other liver function markers in patients treated up to 48 weeks.