Presentation (CTI)

OBJECTIVES: To compare the projected clinical effectiveness of odevixibat versus maralixibat in patients with Alagille syndrome (ALGS), focusing on pruritus response, durability, and downstream clinical outcomes including disease progression and liver transplantation.
METHODS: A comparative effectiveness analysis was conducted using data from the Phase III randomized-control ASSERT and open-label extension ASSERT-EXT trials for odevixibat (NCT04674761/NCT05035030) and an unanchored matching-adjusted indirect comparison (MAIC), adjusting for cross-trial differences in baseline characteristics, informed by the Phase IIb ICONIC trial for maralixibat (NCT02160782). The key clinical endpoint was pruritus response (≥1-point reduction in morning pruritus score). A state-transition (Markov) model was developed to simulate disease progression across ALGS health states, including pruritus responder, pruritus non-responder, cirrhosis, portal hypertension, ascites, liver transplantation, and post-transplant. Transition probabilities between health states and mortality rates were informed by published literature. Response status was linked to disease progression through model transitions, with only non-responders progressing to advanced liver disease states. Differences in treatment response were translated into long-term outcomes, including time spent in the responder state and cumulative liver transplantation rates over multiple time horizons. Scenario analyses explored uncertainty around response, durability, and progression assumptions.
RESULTS: Odevixibat demonstrated higher pruritus response compared with maralixibat at Week 48 (87.18% vs 75.0%), resulting in a higher proportion of patients remaining in the responder state over time. Model projections indicated reduced progression to advanced liver disease and lower cumulative liver transplantation rates with odevixibat. At 5 years, 12.1% of patients receiving odevixibat underwent transplantation compared with 26.5% for maralixibat; at 20 years, rates were 47.5% versus 66.1%, respectively.
CONCLUSIONS: Odevixibat was associated with improved and more durable pruritus response compared with maralixibat. Model-based projections suggest that improved pruritus control may translate into reduced disease progression and lower liver transplantation rates, supporting the potential long-term clinical value of odevixibat in ALGS.