The Food and Drug Administration (FDA) has approved Bylvay™ (odevixibat) for the treatment of pruritus in patients 3 months of age and older with progressive familial intrahepatic cholestasis (PFIC).
Bylvay, an oral, potent, reversible inhibitor of the ileal bile acid transporter (IBAT), works by decreasing the reabsorption of bile acids (primarily the salt forms) from the terminal ileum. The complete mechanism by which odevixibat improves pruritus in PFIC patients is unknown, but the Company believes that inhibition of the IBAT may be involved. Bylvay may not be effective in PFIC type 2 patients with ABCB11 variants resulting in nonfunctional or complete absence of bile salt export pump protein.
The approval was supported by efficacy and safety data from two phase 3 studies, PEDFIC 1 (ClinicalTrials.gov Identifier: NCT03566238) and PEDFIC 2 (ClinicalTrials.gov Identifier: NCT03659916). PEDFIC 1 was conducted in 62 pediatric patients aged 6 months to 17 years with a confirmed molecular diagnosis of PFIC type 1 or type 2 and presence of pruritus at baseline. Patients were randomly assigned to receive odevixibat 40mcg/kg (n=23) or 120mcg/kg (n=19) orally once daily for 24 weeks or placebo.
A single-item observer-reported outcome was used to measure patients’ scratching as observed by their caregiver twice daily; scratching was assessed on a 5-point ordinal response scale (0, no scratching; 4, worst possible scratching).
Results showed treatment with odevixibat demonstrated greater improvement in pruritus compared with placebo (mean percentage of assessments over the treatment period scored as 0 or 1: 35.4% with 40mcg/kg; 30.1% with 120mcg/kg; 13.2% with placebo). Odevixibat was also associated with a significant reduction in serum bile acids compared with placebo (P =.003).
The open-label PEDFIC 2 extension study evaluated the efficacy and safety of odevixibat in patients with PFIC who successfully completed the PEDFIC 1 study. Patients received odevixibat 120mcg/kg once daily. Results demonstrated sustained reductions in serum bile acids as well as improvements in pruritus assessments up to 48 weeks.
The most common adverse reactions reported with odevixibat treatment were liver test abnormalities, diarrhea, abdominal pain, vomiting, and fat-soluble vitamin deficiency.
Bylvay is supplied as 200mcg and 600mcg oral pellets for patients weighing less than 19.5kg and as 400mcg and 1200mg capsules for patients weighing at least 19.5kg.
Commenting on the approval, Richard Thompson, Professor of Molecular Hepatology at King’s College London and principal investigator of PEDFIC 1 and PEDFIC 2, said, “Bylvay gives us a nonsurgical option and will change how we treat PFIC. With this approval, my colleagues and I now have the opportunity to revisit how PFIC patients are being managed and we are hopeful for better outcomes for these children.”
The Company expects to launch Bylvay immediately.
- Albireo announces FDA approval of Bylvay™ (odevixibat), the first drug treatment for patients with progressive familial intrahepatic cholestasis (PFIC). News release. Albireo Pharma, Inc. Accessed July 20, 2021. https://www.globenewswire.com/news-release/2021/07/20/2266030/0/en/Albireo-Announces-FDA-Approval-of-Bylvay-odevixibat-the-First-Drug-Treatment-for-Patients-With-Progressive-Familial-Intrahepatic-Cholestasis-PFIC.html.
- Bylvay [package insert]. Boston, MA: Albireo Pharma, Inc.; 2021.