Bylvay's Sustained Impact: Improving Lives in PFIC and ALGS

Bylvay® (odevixibat), a novel medication developed by Ipsen, has shown promising results in managing severe itch and reducing serum bile acid levels in patients with Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille Syndrome (ALGS). This article delves into the latest data from open-label extension studies, highlighting Bylvay's long-term efficacy and safety profile.

PFIC and ALGS are rare cholestatic liver diseases characterized by severe itching, liver damage, and other debilitating symptoms. Bylvay, an ileal bile acid transport inhibitor, works by reducing the reabsorption of bile acids in the small intestine, thereby lowering serum bile acid levels and alleviating pruritus.

In the PEDFIC 2 study, an open-label extension of the Phase III PEDFIC 1 trial, Bylvay demonstrated sustained reductions in pruritus and serum bile acid levels over 72 weeks. Forty-two percent of patients under 18 years old with PFIC 1 and 2 who transitioned to Bylvay at week 24 experienced a clinically meaningful 1-point reduction in pruritus score. Similarly, 61% of patients with any type of PFIC and of any age excluding episodic showed a similar reduction. The mean change in serum bile acid levels was -104.00 µmol/L for patients who transitioned to Bylvay at week 24 and -57.97 µmol/L for Bylvay-treated patients.

The ASSERT-EXT study, an open-label extension of the Phase III ASSERT trial, evaluated Bylvay's long-term efficacy and safety in ALGS patients. Sustained improvements were observed in pruritus and serum bile acid levels through 72 weeks. At week 72, 93% of patients who received Bylvay throughout the 24 weeks of the ASSERT trial and 77% of those who transitioned from placebo to Bylvay at week 24 experienced a clinically meaningful ≥1 point reduction in pruritus score. The mean reduction in serum bile acid levels was 124 µmol/L for patients who continuously received Bylvay and 139 µmol/L for patients who transitioned from placebo to Bylvay.



Bylvay's safety profile in both studies was consistent and favorable, with most adverse events reported as mild or moderate. The most common adverse events were gastrointestinal, including diarrhea, which was reported in 12% of patients in the PEDFIC 2 study. Only two cases of diarrhea led to treatment interruption or discontinuation.

Expert opinions from Dr. Richard J. Thompson, Professor of Molecular Hepatology at King's College London, and Dr. Nadia Ovchinsky, Chief of the Division of Gastroenterology and Hepatology at Hassenfeld Children's Hospital at NYU Langone, underscore the significance of Bylvay's sustained efficacy and safety profile in managing symptoms like severe itch and reducing serum bile acid levels in these rare cholestatic liver diseases.

In conclusion, Bylvay's data shows sustained improvement in severe itch and serum bile acid levels in patients with PFIC and ALGS. With a consistent safety profile and positive expert opinions, Bylvay offers hope for better management of these debilitating conditions. As Ipsen continues to invest in and develop Bylvay, the potential for improved patient outcomes and market growth in the rare cholestatic liver disease market is significant.