Update on E.U. marketing authorization application for Bylvay for cholestatic pruritus in patients with Alagille syndrome

The Committee for Orphan Medicinal Products (COMP), a scientific committee of the EMA, has concurrently issued a negative opinion for the maintenance of Bylvay’s orphan drug designation in ALGS. This negative COMP opinion prevents the retention of orphan-drug status in Bylvay’s marketing authorization in ALGS and might delay a final European Commission decision. Ipsen plans to submit an appeal in respect of the COMP opinion.

Bylvay, is an orphan medicine already approved in the E.U. for the treatment of progressive familial intrahepatic cholestasis (PFIC) in patients aged six months or older. In November 2022, a variation application to the current market authorization was submitted. The application sought approval in the E.U. for a second orphan indication for Bylvay, the treatment of pruritus in patients with ALGS. In 2012, Bylvay received orphan designation for the treatment of ALGS in the E.U., which supported the development of Bylvay through preclinical and clinical stages.

The CHMP and COMP reviewed data from the Bylvay clinical-trial program, including ASSERT, a double-blind, randomized, placebo-controlled Phase III, multi-center efficacy and safety trial conducted in ALGS. Positive data from ASSERT presented at the 2023 European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) congress, demonstrated that Bylvay provided highly statistically significant and clinically meaningful improvements in pruritus, starting as early as one week after initiation of treatment and were sustained over the 24 weeks of the trial. More than 90% of patients were pruritus responders (greater than one point change at any time during 24 weeks). The overall incidence of treatment-emergent adverse events was similar to placebo. No patients discontinued the trial, and 96% of patients rolled over into the open-label extension trial.