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 (pruritus) and serum bile acid levels, along with positive effects on growth and sleep, over at least 72 weeks of treatment.
Sustained Efficacy in PFIC Patients (PEDFIC 2 Study)
The PEDFIC 2 study, an open-label extension of the PEDFIC 1 trial, evaluated the long-term efficacy and safety of odevixibat in PFIC patients. Dr. Richard J. Thompson, Professor of Molecular Hepatology, King’s College London and principal investigator of the PEDFIC 2 trial, noted that the data suggest the initial reductions in pruritus and serum bile acid levels achieved with odevixibat are sustained long-term. The study included 116 patients, with 83 completing 72 weeks of treatment.
Key findings from PEDFIC 2 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 odevixibat 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 from patients who transitioned to odevixibat at week 24 (n=15) was -104.00 μmol/L, and for Bylvay-treated patients (n=43) was -57.97 μmol/L.
- Improvements in height, weight, and sleep were also reported at 72 weeks in Bylvay-treated patients.
The most common adverse events were gastrointestinal (17.2%), including diarrhea (12%), which led to one treatment interruption and one discontinuation.
Long-Term Benefits in ALGS Patients (ASSERT-EXT Study)
The ASSERT-EXT study assessed the long-term efficacy and safety of Bylvay in ALGS patients. Dr. Nadia Ovchinsky, Chief, Division of Gastroenterology and Hepatology, Hassenfeld Children's Hospital at NYU Langone, New York, and principal investigator of the ASSERT trial, highlighted the encouraging sustained improvements in Bylvay-treated individuals with ALGS, particularly in managing pruritus.
Key results from the ASSERT-EXT study (n=50, with 44 completing 72 weeks) 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 in patients treated with Bylvay for 72 weeks, with a mean reduction of 124 μmol/L in those continuously receiving 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 observed from weeks 24 to 72 across all four sleep parameters.
The safety profile was consistent with the ASSERT trial, with most adverse events being mild or moderate. Diarrhea was the most common treatment-emergent adverse event (TEAE).
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 12 months and older with ALGS and in patients 3 months and older with PFIC. In the EU, it is approved for PFIC in patients aged 6 months or older and for cholestatic pruritus in ALGS patients aged 6 months or older (marketed as Kayfanda for ALGS in the EU).
