Odevixibat improves pruritus, reduces bile acids in children with ALGS

Treatment with odevixibat, a potent, selective IBAT* inhibitor, significantly improved pruritus and reduced serum bile acid levels in children with Alagille syndrome (ALGS), according to the ASSERT** trial presented at The Liver Meeting 2022.

Pruritus severity was significantly improved with odevixibat as shown by a greater reduction in scratching score from baseline to weeks 21–24 (least squares [LS] mean change, -1.7 vs -0.8; p=0.0024). [The Liver Meeting 2022, abstract 38786]

Significantly more patients treated with odevixibat achieved a ≥1-point reduction in monthly scratching score at week 24 relative to placebo (80 percent vs 35 percent; p=0.0012), reported principal trial investigator Dr Nadia Ovchinsky from the Children’s Hospital at Montefiore in New York, New York, US.

In terms of the key secondary endpoint, bile acid levels substantially reduced at weeks 20–24 with the use of odevixibat but increased with placebo (LS mean change, –90 vs 22 µmol/L; p=0.0012).

Additionally, these results corresponded with a positive impact on sleep parameters, another secondary endpoint, which assessed days with soothing (p≤0.001), days with help falling asleep (p≤0.01), and days sleeping with a caregiver (p≤0.01), among others. These changes occurred as early as weeks 1–4 and continued to improve through week 24, favouring the odevixibat arm over the placebo arm.

“The robust results from this trial are important because physicians urgently need more options in the treatment of ALGS. Odevixibat reduced the devastating pruritus, which is so common among this patient population and critical to helping us improve sleep, among other burdens of the disease,” said Ovchinsky in a statement. [https://ir.albireopharma.com/news-releases/news-release-details/albireo-reports-positive-topline-data-phase-3-trial-bylvayr]

“The reduction in serum bile acid levels could indicate that odevixibat may diminish the severity of liver disease over time, which is an important consideration for me as a treating physician,” she added.

This phase III, double-blind, placebo-controlled trial involved 52 patients with ALGS (median age 6.3 years, 52 percent male) who had a mean baseline pruritus score of 2.9. Participants were randomized to receive either odevixibat 120 µg/kg/day (n=35) or placebo (n=17) for 24 weeks.

With regard to safety, the overall incidence of treatment-emergent adverse events (TEAEs) was similar between the odevixibat and placebo arms (74 percent vs 71 percent).

Odevixibat was generally well tolerated, with no deaths or TEAEs leading to study drug discontinuation reported.

“Overall, odevixibat treatment led to significant, rapid, clinically meaningful, and sustained improvements in pruritus, with significant reductions in bile acids and improvements in sleep quality in patients with ALGS,” said Ovchinsky.

“This study met its objectives of demonstrating the efficacy and safety of odevixibat in patients with ALGS,” she added.

*IBAT: Ileal bile acid transporter