INDIRECT TREATMENT COMPARISON OF ODEVIXIBAT AND MARALIXIBAT FOR THE TREATMENT OF CHOLESTATIC PRURITUS IN PATIENTS WITH ALAGILLE SYNDROME (ALGS)
Author(s)
Emmanuelle Kaltenbach, PharmD1, Alice GUIRAUD-DIAWARA, MSc2, Jérémie Schwarzbard, MSc2, Danielle Dray, MD3, Cecile Artaud, MS2.
1Ipsen, London, United Kingdom, 2Ipsen, Paris, France, 3Ipsen, Cambridge, MA, USA.
1Ipsen, London, United Kingdom, 2Ipsen, Paris, France, 3Ipsen, Cambridge, MA, USA.
OBJECTIVES: This study compared efficacy and safety of odevixibat versus maralixibat in patients with ALGS, focusing on pruritus, serum bile acids (sBA), health-related quality of life (HRQoL) and adverse events (AEs).
METHODS: This regression-adjusted matching comparison used patient-level odevixibat data from the phase III randomized-control study ASSERT and open-label extension ASSERT-EXT (NCT04674761/NCT05035030), with published maralixibat data from the phase IIb ICONIC study (NCT02160782). Analyses were conducted at 48 weeks on change from baseline in sBA, morning pruritus score, and Pediatric Quality of Life Inventory (PedsQL) total score, and between Weeks 23/24−48 on incidence of serious AEs (SAEs), gastrointestinal events, abdominal pain, diarrhea, and vomiting. Matching factors included age, sex, baseline sBA, and baseline morning pruritus score. Regression included the same factors, with baseline bilirubin added for sBA and safety analyses and baseline PedsQL total score added for HRQoL comparison. Regression analyses of vomiting and abdominal pain did not converge; therefore, a matching-adjusted indirect comparison was conducted using the same factors.
RESULTS: Odevixibat was associated with numerically greater improvements in morning pruritus score (mean difference [MD]=-0.50; 95%CI=-1.04-0.05) and greater reductions in sBA levels at Week 48 than maralixibat (MD=-26.94 μmol/L; 95%CI=-97.04-43.17), and a statistically significant improvement in Week 48 PedsQL total score (MD=14.64; 95%CI=5.70-23.58). Odevixibat was associated with significantly fewer incidences of gastrointestinal events (odds ratio [OR]=0.22; 95%CI=0.06-0.87; p=0.0311) and abdominal pain (OR=0.06; 95%CI=0.00-0.83; p=0.0361). A trend toward improved tolerability was observed based on SAEs (OR=0.20; 95%CI=0.01-3.50), diarrhea (OR=0.40; 95%CI=0.06-2.62), and vomiting (OR=0.14; 95%CI=0.01-2.11).
CONCLUSIONS: In patients with ALGS, odevixibat demonstrated numerically greater improvements in pruritus and sBA, and significantly enhanced HRQoL versus maralixibat. Odevixibat exhibited superior tolerability for gastrointestinal events and abdominal pain. This is the first analysis applying regression-adjusted matching methodology to robustly and indirectly compare efficacy and safety between odevixibat and maralixibat in ALGS.
METHODS: This regression-adjusted matching comparison used patient-level odevixibat data from the phase III randomized-control study ASSERT and open-label extension ASSERT-EXT (NCT04674761/NCT05035030), with published maralixibat data from the phase IIb ICONIC study (NCT02160782). Analyses were conducted at 48 weeks on change from baseline in sBA, morning pruritus score, and Pediatric Quality of Life Inventory (PedsQL) total score, and between Weeks 23/24−48 on incidence of serious AEs (SAEs), gastrointestinal events, abdominal pain, diarrhea, and vomiting. Matching factors included age, sex, baseline sBA, and baseline morning pruritus score. Regression included the same factors, with baseline bilirubin added for sBA and safety analyses and baseline PedsQL total score added for HRQoL comparison. Regression analyses of vomiting and abdominal pain did not converge; therefore, a matching-adjusted indirect comparison was conducted using the same factors.
RESULTS: Odevixibat was associated with numerically greater improvements in morning pruritus score (mean difference [MD]=-0.50; 95%CI=-1.04-0.05) and greater reductions in sBA levels at Week 48 than maralixibat (MD=-26.94 μmol/L; 95%CI=-97.04-43.17), and a statistically significant improvement in Week 48 PedsQL total score (MD=14.64; 95%CI=5.70-23.58). Odevixibat was associated with significantly fewer incidences of gastrointestinal events (odds ratio [OR]=0.22; 95%CI=0.06-0.87; p=0.0311) and abdominal pain (OR=0.06; 95%CI=0.00-0.83; p=0.0361). A trend toward improved tolerability was observed based on SAEs (OR=0.20; 95%CI=0.01-3.50), diarrhea (OR=0.40; 95%CI=0.06-2.62), and vomiting (OR=0.14; 95%CI=0.01-2.11).
CONCLUSIONS: In patients with ALGS, odevixibat demonstrated numerically greater improvements in pruritus and sBA, and significantly enhanced HRQoL versus maralixibat. Odevixibat exhibited superior tolerability for gastrointestinal events and abdominal pain. This is the first analysis applying regression-adjusted matching methodology to robustly and indirectly compare efficacy and safety between odevixibat and maralixibat in ALGS.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
SA44
Topic
Study Approaches
Topic Subcategory
Meta-Analysis & Indirect Comparisons
Disease
SDC: Gastrointestinal Disorders, SDC: Rare & Orphan Diseases