An interim analysis of data from the ASSERT-EXT study demonstrated that in patients with Alagille syndrome (ALGS), treatment with odevixibat was associated with long-term safety and efficacy, including rapid improvements in sleep disturbance and pruritus, along with reduced bile acid concentrations.

Findings from the ongoing, phase 3, open-label extension ASSERT-EXT study were presented at the 55th Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), which was held in Vienna, Austria, from May 17 to 20, 2023.

Patients who had previously been enrolled in the 24-week, phase 3, placebo-controlled ASSERT study were eligible to enter ASSERT-EXT. All of the participants in ASSERT-EXT were treated with 120 μg/kg/day of odevixibat, an ileal bile acid transporter inhibitor. The following 2 groups of participants in ASSERT-EXT were evaluated through an interim cutoff date of September 9, 2022:

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  • Treatment-naive patients who had been treated with placebo in ASSERT (placebo-odevixibat group)
  • Odevixibat-treated patients in ASSERT (odevixibat-odevixibat group)

In ASSERT-EXT, pruritus, serum bile acid levels, sleep, and treatment-emergent adverse events (TEAEs) were assessed. Forty-nine patients had received treatment in ASSERT-EXT at the cutoff date—32 in the odevixibat-odevixibat arm and 17 in the placebo-odevixibat arm.

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Individuals in the odevixibat-odevixibat group entered the ASSERT-EXT study with improved pruritus, decreased bile acid concentrations, and enhanced sleep findings. With longer treatment in ASSERT-EXT, these parameters displayed uniform, sustained improvements.

Participants in the placebo-odevixibat group exhibited mean reductions in pruritus, as observed with improvements in scratching score. In fact, a pruritus reduction of 1 point or more from baseline was attained in 70% of participants in the placebo-odevixibat arm at weeks 9 to 12 of ASSERT-EXT. Both the placebo-odevixibat group and the odevixibat-odevixibat group demonstrated mean reductions in the percentage of days required for soothing or help falling asleep.

TEAEs were mostly mild to moderate in severity. Serious TEAEs were reported in 4% (2 of 49) of the study participants in ASSERT-EXT. The incidences of treatment-emergent diarrhea and drug-related diarrhea were 16% and 4%, respectively. There were no drug-associated serious TEAEs, nor any TEAEs that necessitated treatment discontinuation or dose reduction of odevixibat.

“Consistent with results from ASSERT, an interim analysis of ASSERT-EXT data showed that treatment-naive patients with ALGS had rapid improvements in pruritus, sleep, and bile acids with odevixibat; patients previously treated with odevixibat showed sustained improvements in these outcomes with continued treatment,”  the researchers explained. “Odevixibat treatment for ≥24 weeks in patients with ALGS was well tolerated,” they concluded.

Reference

Ovchinsky N. Efficacy and safety of odevixibat in patients with Alagille syndrome: interim results from the open-label, phase 3 ASSERT-EXT study. Presented at: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 55th Annual Meeting, May 17-20, 2023; Vienna, Austria. Abstract H-0023.

Albireo Pharma ASSERT-EXT study Bylvay® Cardiologists Gastroenterologists Hepatologists Nephrologists odevixibat