Introduction: In the 24-week, phase 3 ASSERT study (NCT04674761), odevixibat significantly lowered pruritus and serum bile acids (sBAs) in patients with Alagille syndrome (ALGS). Here, we report long-term data on odevixibat efficacy and safety from the 72-week, open-label ASSERT-EXT study (NCT05035030).

Method: Patients who completed ASSERT were eligible to enter ASSERT-EXT; all patients in ASSERT-EXT received odevixibat 120 μg/kg/day. Outcomes included change in pruritus score, change in sBAs, and treatment-emergent adverse events (TEAEs). Results were evaluated in patients who received odevixibat in ASSERT and ASSERT-EXT (ODX/ODX) and patients who received placebo in ASSERT and odevixibat in ASSERT-EXT (PBO/ODX); baseline was pre‑odevixibat (ASSERT baseline for ODX/ODX and ASSERT-EXT baseline for PBO/ODX).

Results: Of 52 patients who completed ASSERT, 50 (median [range] age, 5.5 [1.0−15.9] years) entered ASSERT‑EXT (ODX/ODX, n=33; PBO/ODX, n=17). Mean (SD) changes in pruritus score from baseline to weeks 69−72 of ASSERT-EXT were −2.2 (0.9) points (ODX/ODX; P<0.0001) and −1.7 (0.8) points (PBO/ODX; P<0.0001; Figure A). Mean (SD) changes in sBAs from baseline to week 72 of ASSERT-EXT were −124 (136) µmol/L (ODX/ODX) and −139 (101) µmol/L (PBO/ODX; Figure B). The most common drug-related TEAE was diarrhea (ODX/ODX: 2/33 [6%]; PBO/ODX: 3/17 [18%]).

Conclusion: Odevixibat significantly improved pruritus and reduced sBA levels in patients with ALGS; these improvements were sustained for up to 96 weeks in patients who remained on odevixibat. The safety profile of odevixibat in ASSERT-EXT was consistent with that in ASSERT. These robust long-term data demonstrate durable efficacy and tolerability of odevixibat in patients with ALGS.