Ryan T. Fischer, MD: Long-Term Odevixibat Benefit for Alagille Syndrome


Pooled data from The Liver Meeting showed odevixibat sustains itch and serum bile acid benefits in patients with Alagille syndrome. An investigators shares what he wants to learn next.

Pooled data presented earlier this weekend at The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD) in Boston showed odevixibat (Bylvay) provided maintained reduction in pruritus severity and serum bile acid levels among treated patients with Alagille syndrome though 36 weeks.

The combined findings from the phase ASSERT and ongoing open-label ASSERT-EXT trial elucidate the primary, and continued, benefits of the ileal bile acid transporter (IBAT) inhibitor odevixibat in children with the burdensome, rare, genetic cholestatic disease.

In an interview with HCPLive during The Liver Meeting this weekend, study author Ryan T. Fischer, MD, chief of hepatology and transport medicine at Children’s Mercy Kansas City, discussed the real-world impact of the new ASSERT findings as they relate to managing pediatric patients with Alagille syndrome.

“It's knowing that when you do have a patient with Alagille syndrome, you do have the ability to prescribe odevixibat to help reduce the burden of that itch that those kids may feel,” Fischer said. “We know that for those patients, it's one of the most life-altering, quality of life-changing effects of that disease for them—that severe itch that they feel.”

Many parents and guardians report to Fischer and colleagues that the itch symptom associated with the condition is so persistent and severe that, in some cases, young children will cause themselves to bleed from constant scratching. Odevixibat is among a drug class showing capability to resolve the issue significantly and rapidly.

“What's nice is that when we do use these bile acid transport inhibitors, we see that those itch scores go down and they do go down relatively quickly,” Fischer said. “And then they seem to be sustained, at least over the course of those study periods, which are still ongoing for odevixibat.”

Regarding the ongoing extension assessment, Fischer said the ultimate long-term treatment assessment goal for odevixibat is to interpret management of Alagille syndrome without patient need for liver transplant.

“That's where we see, especially in Alagille syndrome, one of the primary indications for liver transplant—or at least one of the indications that seems to be across the board for those kids—is pruritis,” Fischer said. “Their liver may actually be working okay, doing a lot of its jobs, producing those proteins. But they may be so itchy...and have such a disrupted quality of life and quality of their sleep, that transplant seems like it's really the option that they have to take because of it.”

Datasets for the IBAT inhibitor do show improved survival without transplantation in treated patients, he noted, and that it’s likely in part due to the positive effect on patient itch and quality of life. Regarding serum bile acid level improvement, Fischer said the outcome is indirectly associated to the effect of pruritus—and indistinctly to disease management—but that more research into treating cholestatic disease with IBAT inhibitors may elucidate the true meaning of that benefit further.

“We know there's other trials in place for other disease processes,” Fischer said. “I'd be excited, probably more in the near future, thinking about how else we can we use these types of bile acid transport inhibitors, or modifications of that bile acid pool in general, to help other liver diseases that especially that kids suffer from.”


Ovchinsky N, Aumar M, Baumann U, Bufler P, et al. Individual pruritus and bile acid responses over time with odevixibat treatment: pooled data from the phase 3 ASSERT and ASSERT-EXT studies in patients with Alagille syndrome. Paper presented at: The Liver Meeting. Boston, MA. November 10 - 14, 2023.

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