Nadia Ovchinsky, MD: Odevixibat's Phase 3 Data and Potential for Alagille Syndrome

Next week, the US Food and Drug Administration (FDA) will deliberate on the supplemental New Drug Application (sNDA) from Albireo for odevixibat (Bylav), as a treatment for patients with the rare, inherited Alagille syndrome.¹

The ileal bile acid transporter (IBAT) inhibitor agent was previously supported by phase 3 data from the ASSERT trial, showing a 24-week regimen of 120 μg/kg/day odevixibat was associated with a mean change of -1.7 in baseline patient-reported scratching score, versus only -0.8 among patients receiving placebo—indicating significant benefit in disease-associated pruritus (P = .0024).²

The phase 3 trial also showed that the generally pediatric patient population receiving odevixibat had significant improvement in bile acid count (P = .0012) and instances of needing help falling asleep (P <.01) versus patients receiving placebo over 24 weeks.

Altogether, the combination of patient- and guardian-reported outcomes and clinical improvement indicate an opportunity to change the landscape of care strategy for pediatric patients with Alagille syndrome.

In the second segment of an interview with HCPLive, ASSERT investigator Nadia Ovchinsky, MD, director of the division of pediatric gastroenterology and hepatology in the department of pediatrics at NYU Grossman School of Medicine, discussed the significance of the ASSERT trial data and how they relate to real-world Alagille syndrome management.

“The results of reduction in pruritus were very early onset; they were statistically significant, and also they were clinically meaningful to our patient population,” Ovchinsky explained. “Reduction in bile acid levels was a key secondary outcome, and probably one of the most important things we saw in this trial…was the effect on sleep parameters.”

Ovchinsky stressed that sleep parameters in this patient population is an “important reflection of quality of life for children, but also for families.”

“It’s also impressive just to hear feedback from parents…that families saw a significant reduction in all the efforts it took for the kids to go to sleep, for the kids to pay in attention in class or at home due to a decrease in pruritus,” she said.

Headed into the PDUFA date for odevixibat next week, Ovchinsky discussed prospectively the benefit of multisystemic drugs on patients with Alagille syndrome.

“It’s great to have medications that can have real impact on patients and family,” Ovchinsky said. “Up until IBAT inhibitors were developed, all we had for these challenging patient populations are medications that didn’t really work and surgical options like liver transplant.”

The latter strategy is a key pain point for Ovchinsky and colleagues, who struggle to deliver a liver transplant for patients on the basis of their itch symptoms being too burdensome.

“To have a drug that may change the landscape of why we need a transplant in this patient population would be incredible,” she said.

References

1. ^{Albireo. FDA Grants June 15, 2023 PDUFA Date to Albireo for Bylvay® in Alagille Syndrome. News release. Published February 14, 2023. https://ir.albireopharma.com/news-releases/news-release-details/fda-grants-june-15-2023-pdufa-date-albireo-bylvayr-alagille}
2. ^{Ovchinsky N. Efficacy and safety of odevixibat in patients with Alagille syndrome: top-line results from ASSERT, a phase 3, double-blind, randomized, placebo-controlled study. Presented at: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 55th Annual Meeting, May 17-20, 2023; Vienna, Austria. Abstract H-0023.}