Bylvay Demonstrates Sustained Improvement in Itch and Bile Acid Levels in PFIC and ALGS Patients

Key Insights

• Long-term data from Phase III open-label extension studies show Bylvay (odevixibat) provides sustained efficacy in treating Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille syndrome (ALGS).
• Patients treated with Bylvay for at least 72 weeks experienced improvements in height, weight, and sleep, alongside sustained reductions in pruritus and serum bile acid levels.
• In the PEDFIC 2 study, a clinically meaningful reduction in pruritus score was observed in 42% of PFIC patients under 18 and 61% across various PFIC subtypes.

Ipsen announced new data at the American Association for the Study of Liver Diseases (AASLD) demonstrating the long-term efficacy and safety of Bylvay (odevixibat) in patients with Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille syndrome (ALGS). The data, derived from two Phase III open-label extension studies (PEDFIC 2 and ASSERT-EXT), revealed sustained improvements in severe itch and serum bile acid levels over at least 72 weeks of treatment.

Sustained Efficacy in PFIC Patients (PEDFIC 2 Study)

The PEDFIC 2 study (n=116) evaluated the efficacy and safety of Bylvay over 72 weeks. Key findings include:

• A clinically meaningful 1-point reduction in pruritus score at week 72 was observed in 42% of patients &LT18 years old with PFIC 1 and 2 who transitioned to Bylvay at 24 weeks (n=5/12) and 61% of patients with any type of PFIC and of any age excluding episodic (n=19/31).
• Patients who remained on treatment sustained rapid initial pruritus score improvements achieved by week 4.
• At 72 weeks, the mean change in serum bile acid (sBA) levels was -104.00 µmol/L for patients who transitioned to Bylvay at week 24 (n=15) and -57.97 µmol/L for Bylvay-treated patients (n=43).

Dr. Richard J. Thompson, Professor of Molecular Hepatology, King’s College London and principal investigator of the PEDFIC 2 trial, noted, “These open-label extension data from PEDFIC 2 suggest that the initial reduction in pruritus and in serum bile acid levels achieved following initiation of odevixibat are being sustained into the longer term. We are also observing reductions in both pruritus and serum bile acid across a number of PFIC subtypes.”

Improvements in ALGS Patients (ASSERT-EXT Study)

The ASSERT-EXT study (n=50) assessed the long-term efficacy and safety of Bylvay in ALGS patients (ages 1-15.9 years) through 72 weeks. Notable results include:

• At week 72, 93% (n=28/30) of patients who received Bylvay throughout the 24 weeks ASSERT trial and 77% (n=10/13) of those who transitioned from placebo to Bylvay at week 24 experienced a clinically meaningful ≥1 point reduction in pruritus score.
• Patients treated with Bylvay for 72 weeks showed a mean reduction in sBA levels of 124 µmol/L in those who continuously received Bylvay and a mean reduction of 139 µmol/L in patients who transitioned from placebo to Bylvay.
• Mean changes from baseline were observed in height (8.2 cm) and weight (2.8 kg) on continuous Bylvay use, and for patients who transitioned from placebo to Bylvay, height (10.7 cm) and weight (3.3 kg) mean changes were also reported.

Dr. Nadia Ovchinsky, Chief, Division of Gastroenterology and Hepatology, Hassenfeld Children’s Hospital at NYU Langone, commented, “The sustained improvements we’ve seen in Bylvay-treated individuals living with Alagille syndrome are encouraging. These results not only show the potential to manage symptoms like pruritus, which can be extremely difficult for children and their parents to manage, but we’re also seeing a consistent safety profile over the longer term with sustained tolerability.”

Safety and Tolerability

Across both studies, Bylvay demonstrated a consistent safety profile. Most adverse events were mild or moderate, with diarrhea being the most common. In PEDFIC 2, gastrointestinal events were reported in 17.2% of patients, with diarrhea in 12%. In ASSERT-EXT, treatment-emergent adverse events occurred in 18% of patients who continuously received Bylvay and 41% of those who transitioned from placebo to Bylvay.

About Bylvay (odevixibat)

Odevixibat, marketed as Bylvay, is a once-daily, non-systemic ileal bile acid transport (IBAT) inhibitor. It is approved in the U.S. and Europe for the treatment of cholestatic pruritus in patients with PFIC and ALGS. Bylvay works by reducing the reabsorption of bile acids, thereby decreasing serum bile acid levels and alleviating associated symptoms like pruritus.

Sandra Silvestri, EVP Chief Medical Officer, Ipsen, stated, “Data suggesting Bylvay-treated patients experienced sustained efficacy, and which support the safety and tolerability profile seen in previous clinical trials, are important. Ipsen is committed to being the leader across rare cholestatic liver diseases and we are just getting started.”