Long-term odevixibat shows sustained benefits in ALGS

Long-term treatment with odevixibat led to sustained improvements in pruritus scores and reductions in serum bile acid (sBA) levels among patients with Alagille syndrome (ALGS), based on a pooled analysis of the phase III ASSERT and ASSERT-EXT studies presented at ESPGHAN 2025.

This analysis included 52 patients (median age 5.7 years, 27 percent male) diagnosed with ALGS who were randomly assigned to receive either odevixibat (n=35) or placebo (n=17) for 24 weeks in the double-blind ASSERT study, followed by an additional 72 weeks of odevixibat treatment for all patients in the open-label ASSERT-EXT study.

With a median treatment duration of 1.9 years, patients who remained on odevixibat treatment for 96 weeks experienced a significant improvement in pruritus score, with a mean change from baseline of -2.2 (p<0.0001). [ESPGHAN  2025, abstract EP169]

When patients were stratified according to their baseline sBA and direct bilirubin levels, improvements in pruritus scores were also observed with odevixibat, regardless of whether the patients had an sBA level of ≥212.5 or <212.5 µmol/L (mean change from baseline to weeks 93–96, -1.9 and -2.4, respectively) or a direct bilirubin level of >3 or ≤3 mg/dL (mean change from baseline to weeks 93–96, -1.6 and -2.5, respectively).

Odevixibat-treated patients also had significantly reduced mean sBA levels across all time points (-89 µmol/L at week 24, -119.4 µmol/L at week 72, and -123.9 µmol/L at week 96).

In turn, approximately 63 percent of the participants achieved an sBA level of ≤102 µmol/L, a threshold associated with improved native liver survival, by week 96, according to the researchers.

Over the course of odevixibat treatment, catch-up growth was observed at week 96, with a significant improvement in mean height z-scores from baseline (0.27; p=0.0276). However, mean weight z-scores showed limited to no change from baseline to week 96 (-0.02; p=0.08207).

With regard to hepatic parameters, patients receiving odevixibat initially experienced increases in mean ALT* and AST** levels, which plateaued through week 96 (99.2 U/L; p<0.0001 and 65.9 U/L; p=0.0006, respectively).

“Overall, odevixibat led to rapid and significant improvements in pruritus and reduced sBA levels, which were sustained with long-term treatment,” noted the researchers.

Safety

In terms of safety, serious treatment-emergent adverse events (TEAEs) occurred in 13 participants, mostly mild or moderate, with no deaths reported.

The most common drug-related TEAE was diarrhoea (17.3 percent), though it did not lead to treatment discontinuation.

“No new or unexpected safety findings were observed with odevixibat,” said the researchers.