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New pooled phase 3 and extension trial data show odevixibat continues to improve disease management and itch reduction in children with Alagille syndrome.
Odevixibat (Bylvay) provided improved pruritus and reduced serum bile acid levels in patients with Alagille syndrome for up to 36 weeks, according to interim findings from a combination phase 3 trial and open-label extension.1
In pooled data from the pivotal ASSERT and ASSERT-EXT studies, presented at The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD) in Boston this weekend, investigators reported outcomes showing the ileal bile acid transporter (IBAT) inhibitor provided significant benefit to both primary pathophysiologic and symptomatic characteristics of Alagille syndrome—a rare, genetic cholestatic condition that primarily impacts children and adolescents.
Odevixibat was approved by the US Food and Drug Administration (FDA) to treat cholestatic pruritus in patients ≥1 year old with Alagille syndrome in June, on the basis of findings from the ASSERT trial showing the 24-week, 120 μg/kg/day regimen was associated with a mean -1.7 change in baseline-reported pruritus score—a 0.9-improvement versus patients receiving placebo (P = .0024).2
In the data presented by study author Ryan T. Fischer, MD, of Children's Mercy Kansas City, at The Liver Meeting this week, investigators presented individual patient changes in pruritus and serum bile acids over time with odevixibat across the initial 24-week trial, as well as the ongoing, 72-week open-label ASSERT-EXT that which switched all patients onto 120 μg/kg/day daily odevixibat.
Fischer presented data from a cutoff date of September 9, 2022. Primary endpoints included change over time in clinician-reported itching scores (0 – 4 scale, with higher scores indicating worse itch) as well as serum bile acid levels.
The pooled analysis featured 52 patients treated with odevixibat, of whom 17 were switched from the original placebo arm in the phase 3 ASSERT trial. Median exposure to odevixibat at the data cutoff date was 30 weeks (range, 0.7 – 74). Mean patient age was 6.5 years old; 25 (48%) patients were female.
Mean pruritus score was 2.6 at baseline; mean bile acids were 246 μmol/L. All but 1 patients (98%) were using antipruritus medication at baseline.
Regarding pruritus, investigators observed an immediately score drop from 2.6 at baseline to 1.7 at weeks 1 – 4. By weeks 21 – 24, mean patient score dropped to 1.0, then 0.6 at weeks 33 – 36. Comparatively, patients receiving placebo in ASSERT only decreased from 3.0 at baseline to 2.1 by weeks 21 – 24.
Regarding serum bile acids, investigators again observed a significant, rapid decrease—from 246 μmol/L at baseline to 116 μmol/L at week 4. After an increase in mean bile acids to 145 μmol/L at weeks 20 – 24, levels again significantly decreased to 116 μmol/L by week 36. Among patients receiving placebo in ASSERT, serum bile acids actually increased, from 246 μmol/L at baseline to 271 μmol/L at weeks 20 – 24.
A total of 43 (83%) patients treated with odevixibat reported a treatment-emergent adverse event (TEAE). Another 7 (14%) reported a severe TEAE, however, no patients discontinued the therapy due to a TEAE as of the data cutoff date. The most drug-related TEAEs included diarrhea, abdominal pain, and vomiting.
Though the extension trial is ongoing, Fischer expressed positive conclusions as to the impact of odevixibat on pruritus and serum bile acid management in young patients with Alagille syndrome.
“In patients with ALGS, odevixibat treatment for up to 36 weeks resulted in improvements in pruritus and reduced serum bile acid levels,” Fischer said. “These changes occurred rapidly, with effects sustained over time.”