Ipsen presented data at the American Association for the Study of Liver Diseases (AASLD) demonstrating the long-term efficacy and safety of odevixibat (Bylvay) 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), showed sustained improvements in pruritus and serum bile acid levels, along with positive effects on height, weight, and sleep measures, over at least 72 weeks of treatment.
Sustained Efficacy in PFIC Patients
The PEDFIC 2 study (n=116) evaluated the efficacy and safety of odevixibat over 72 weeks. Results indicated that 42% of patients under 18 years with PFIC 1 and 2 who transitioned to odevixibat at 24 weeks experienced a clinically meaningful 1-point reduction in pruritus score at week 72 (n=5/12). Among patients with any type of PFIC (excluding episodic) and of any age, 61% showed a similar reduction (n=19/31). The mean change in serum bile acid (sBA) levels from baseline at week 72 was -104.00 μmol/L for patients transitioning to odevixibat at week 24 (n=15) and -57.97 μmol/L for those continuously treated with odevixibat (n=43).
According to Dr. Richard J. Thompson, Professor of Molecular Hepatology, King’s College London and principal investigator of the PEDFIC 2 trial, the data suggests that the initial reduction in pruritus and sBA levels achieved with odevixibat is sustained long-term. He also noted the reductions in both pruritus and sBA across various PFIC subtypes, which is important for understanding the therapeutic management of PFIC patients.
Improvements in ALGS Patients
The ASSERT-EXT study (n=50) assessed the long-term efficacy and safety of odevixibat in ALGS patients (ages 1-15.9 years) over 72 weeks. The study found that 93% of patients who received odevixibat throughout the 24-week ASSERT trial (n=28/30) and 77% of those who transitioned from placebo to odevixibat at week 24 (n=10/13) experienced a clinically meaningful ≥1 point reduction in pruritus score at week 72. Reductions in sBA levels were also observed, with a mean reduction of 124 μmol/L in patients continuously receiving odevixibat and 139 μmol/L in those transitioning from placebo to odevixibat.
Mean changes from baseline were observed in height (8.2 cm) and weight (2.8 kg) with continuous odevixibat use. For patients transitioning from placebo to odevixibat, height and weight mean changes were 10.7 cm and 3.3 kg, respectively. Improvements in sleep were also noted across all four sleep parameters from weeks 24 to 72 (n=43).
Dr. Nadia Ovchinsky, Chief, Division of Gastroenterology and Hepatology, Hassenfeld Children's Hospital at NYU Langone, emphasized that the sustained improvements in ALGS patients treated with odevixibat are encouraging. She highlighted the potential to manage symptoms like pruritus and the consistent safety profile observed over the longer term.
Safety and Tolerability
In both studies, most adverse events were mild or moderate. The most common adverse event was gastrointestinal, including diarrhea. In PEDFIC 2, gastrointestinal events were reported in 17.2% of patients (n=20/116), with diarrhea in 12% (n=14/116). In ASSERT-EXT, treatment-emergent adverse events (TEAE) occurred in 18% (n=6/33) of patients continuously receiving odevixibat and 41% (n=7/17) of patients transitioning from placebo to odevixibat, with diarrhea being the most common TEAE.
About Odevixibat
Odevixibat, marketed as Bylvay and Kayfanda, 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.
