Albireo Pharma, Inc. announced the submission of a supplemental New Drug Application to the U.S. Food and Drug Administration (FDA) and a variation application to the European Medicines Agency (EMA) seeking approval for a second Bylvay indication for use in patients with Alagille syndrome in the second half of 2023. A potent, once-daily, non-systemic ileal bile acid transport inhibitor (IBATi), Bylvay has minimal systemic exposure and acts locally in the small intestine. Bylvay is already approved in the U.S. for the treatment of pruritus in patients 3 months of age and older in all types of progressive familial intrahepatic cholestasis (PFIC), and in Europe for the treatment of all types of PFIC in patients aged 6 months or older.

Positive data from the Phase 3 ASSERT study recently presented at the 2022 AASLD The Liver Meeting demonstrated that Bylvay provided early, rapid, clinically meaningful and sustained improvements in pruritus, as well as significant reductions in bile acids and improvements in sleep quality across the two most prominent genetic types in Alagille syndrome, JAG1 and NOTCH2, and in a wider age range of ALGS patients. Over 90% of patients were pruritus responders and Bylvay was generally well tolerated; the overall incidence of treatment emergent adverse events (TEAEs) was similar to placebo . No patients discontinued the study and 96% of patients rolled over into the open-label extension study.

In the U.S., Bylvay received orphan exclusivity for the treatment of pruritus in PFIC and Orphan Drug Designations for the treatment of ALGS, biliary atresia and primary biliary cholangitis. In Europe, Bylvay received orphan exclusivity for the treatment of PFIC and Orphan Drug Designations for the treatment of ALGS, biliary atresia and primary biliary cholangitis. With completed submissions for Bylvay in the U.S. and EU for use in patients with ALGS, the Company anticipates approvals in the second half of 2023.

Bylvay is also being evaluated in the Phase 3 BOLD study in biliary atresia, a global gold standard pivotal trial that enrolled 205 patients. Topline results are expected to be available by the end of 2024. ASSERT Phase 3 Clinical Trial Data ASSERT is a gold standard, prospective intervention trial with 32 sites across North America, Europe, Middle East, and Asia Pacific.

The double-blind, randomized, placebo-controlled trial was designed to evaluate the safety and efficacy of 120 ug /kg/day Bylvay (odevixibat) for 24 weeks in relieving pruritus in patients with Alagille syndrome (ALGS). Key secondary endpoints measure serum bile acid levels and safety and tolerability. The trial enrolled patients aged 0 to 17 years of age with a genetically confirmed diagnosis of ALGS.

In the primary analysis, the study met the primary endpoint showing statistically significant reduction in pruritus as measured by the PRUCISION Observer-Reported Outcome scratching score (0-4 point scale), from baseline at month 6 (weeks 21 to 24), compared to the placebo arm. Over 90% of patients were pruritus responders during the study, as defined as at least a 1-point drop at any time point. The study also met the key secondary endpoint showing a statistically significant reduction in serum bile acid concentration from baseline to the average of weeks 20 and 24.

Statistically significant improvements in multiple sleep parameters were observed as early as week 1-4 compared to patients on placebo with continued improvement through week 24 In the study, there were no patient discontinuations. Bylvay was well tolerated, with an overall adverse event incidence similar to placebo and a low incidence of drug-related diarrhea (11.4% vs. 5.9% placebo).

ALGS & Expanded Access Program Alagille syndrome, or ALGS, is a rare, multisystem genetic disorder that the Company estimates impacts 25,000 people globally. ALGS can affect the liver, heart, skeleton, eyes, central nervous system, kidneys and facial features. Liver damage is caused by a paucity of bile ducts preventing bile flow from the liver to the small intestine.

Approximately 95% of patients with the condition present with chronic cholestasis, usually within the first three months of life, and as many as 88% also present with severe, intractable pruritus.