Ipsen presented 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, from two Phase III open-label extension studies (PEDFIC 2 and ASSERT-EXT), showed sustained improvements in severe itch and serum bile acid levels over 72 weeks.
Sustained Efficacy in PFIC Patients (PEDFIC 2 Study)
The PEDFIC 2 study, an open-label extension of the PEDFIC 1 trial, evaluated the efficacy and safety of Bylvay in 116 patients with PFIC. Key findings include:
- A clinically meaningful 1-point reduction in pruritus score at week 72 was observed in 42% of patients under 18 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 Bylvay treatment maintained rapid initial pruritus score improvements achieved by week 4.
- At 72 weeks, the mean change in serum bile acid (sBA) levels from patients who transitioned to Bylvay at week 24 (n=15) was -104.00 μmol/L, and for Bylvay-treated patients (n=43) it was -57.97 μmol/L.
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. This is important information for our understanding of the therapeutic management of our patients living with PFIC."
Beyond improvements in pruritus and sBA levels, the study also reported increases in height, weight, and sleep measures at 72 weeks in Bylvay-treated patients. The most common adverse events were gastrointestinal, including diarrhea (12%).
Sustained Efficacy in ALGS Patients (ASSERT-EXT Study)
The ASSERT-EXT study evaluated the long-term efficacy and safety of Bylvay in 50 ALGS patients (ages 1-15.9 years) over 72 weeks. Key results showed:
- At week 72, 93% (n=28/30) of patients who received Bylvay throughout the 24-week 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.
- Reductions in sBA levels were observed, with a mean reduction 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.
Improvements in sleep were also observed across all four sleep parameters assessed. The safety profile was consistent with the ASSERT clinical trial, with most adverse events being mild or moderate.
Dr. Nadia Ovchinsky, Chief, Division of Gastroenterology and Hepatology, Hassenfeld Children's Hospital at NYU Langone, stated, "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."
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. for cholestatic pruritus in patients with PFIC (3 months and older) and ALGS (12 months and older). In the EU, it is approved for PFIC (6 months and older) and ALGS (marketed as Kayfanda, 6 months and older).
About PFIC and ALGS
PFIC is a group of rare genetic disorders causing bile acid buildup in the liver, leading to damage and potential liver failure. ALGS is another rare genetic disorder affecting multiple organs, including the liver, heart, skeleton, eyes, and kidneys. Pruritus, resulting from serum bile acid buildup, is a common and debilitating symptom in both conditions.
