Odevixibat shows sustained efficacy and safety in long-term Phase 3 studies for PFIC and Alagille syndrome
Long-term data from two Phase 3 extension studies assessing odevixibat for progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome (ALGS) were presented at the American Association for the Study of Liver Diseases’ 75th Liver Meeting. In the PEDFIC 2 study, odevixibat demonstrated sustained reductions in pruritus and serum bile acids (sBA) after 72 weeks in PFIC patients, along with improvements in height, weight, and sleep.1 In the ASSERT-EXT study, odevixibat showed similar efficacy in ALGS, with significant reductions in pruritus and sBA, and notable improvements in growth and sleep.2 Both studies confirmed the safety profile of odevixibat, with most adverse events being mild to moderate and primarily gastrointestinal.
PEDFIC 2
Long-term treatment with odevixibat provided sustained improvements in serum bile acids, pruritus, and overall quality of life for patients with PFIC, while being well tolerated, according to the new analysis of the PEDFIC 2 study. Odevixibat was also found to reduce the need for surgical interventions and support native liver survival across various PFIC subtypes.
The open-label Phase 3 extension study enrolled 116 patients with various PFIC subtypes. All participants received odevixibat at 120 µg/kg/day. Results after 72 weeks showed rapid and sustained reductions in sBA levels and pruritus, with 72% of patients completing the treatment period. Improvements were observed across all PFIC subtypes, including rare forms such as episodic PFIC.
Longer-term follow-up (up to 4.5 years) showed continued benefits in growth, sleep, and quality of life, alongside high rates of native liver survival (≥77%) and surgery-free survival (≥76%). Gastrointestinal side effects, primarily mild to moderate diarrhea, were the most common adverse events, and only two serious cases required treatment adjustments.
ASSERT-EXT
The 72-week ASSERT-EXT study, evaluating the long-term efficacy and safety of odevixibat in patients with Alagille syndrome (ALGS), also yielded promising results. This follow-up to the 24-week ASSERT study confirmed that odevixibat continues to significantly reduce pruritus and serum bile acids (sBAs) in ALGS patients, with a consistent safety profile.
A total of 50 patients, aged 1 to 15.9 years, who completed the ASSERT study were enrolled in ASSERT-EXT. All participants received odevixibat at 120 µg/kg/day. The primary efficacy measure, change in pruritus score from baseline to weeks 69-72, showed substantial improvement. For those who received odevixibat in both studies (ODX/ODX), pruritus scores decreased by an average of 2.2 points. In comparison, the placebo-to-odevixibat switch group (PBO/ODX) saw a reduction of 1.7 points. Additionally, 93% of the ODX/ODX group and 77% of the PBO/ODX group achieved at least a 1-point reduction in pruritus.
Serum bile acids also improved in both groups, with mean reductions of 124 µmol/L in the ODX/ODX group and 139 µmol/L in the PBO/ODX group.
Safety was consistent with earlier findings, with 18% of ODX/ODX patients reporting drug-related treatment-emergent adverse events compared to 41% of the PBO/ODX group. Diarrhea was the most common treatment-emergent adverse event, affecting 6% and 18% of patients, respectively. No serious adverse events were observed, and one patient in the PBO/ODX group required liver transplantation.
References
- Thompson R, et al. Sustained, long-term efficacy and safety of odevixibat in patients with progressive familial intrahepatic cholestasis. Presented at: The Liver Meeting; November 15-19, 2024; San Diego, CA.
- Ovchinsky N, et al. Assert-EXT: Final data from an open-label, phase 3 study of odevixibat in patients with Alagille syndrome. Presented at: The Liver Meeting; November 15-19, 2024; San Diego, CA.
