FDA Approves Odevixibat for Cholestatic Pruritus in Alagille Syndrome


The approval makes odevixibat the second IBAT inhibitor approved for the rare genetic disease, with capability to benefit both liver damage and itch symptoms.

FDA Approves Odevixibat for Cholestatic Pruritus in Alagille Syndrome

The US Food and Drug Administration (FDA) has approved odevixibat (Byvay) for the treatment of cholestatic pruritus in patients ≥12 months old with Alagille syndrome.

The approval for the ileal bice acid transporter (IBAT) inhibitor, granted to Ipsen, is supported by clinical data showing significant benefit for cholestatic liver disease, as well as patient-reported outcomes like pruritus—a pair of needed benefits in the rare, pediatric-based and potentially deadly Alagille syndrome.

“As an advocate for families impacted by Alagille syndrome, it is such a blessing to know physicians now have another drug treatment option for the debilitating pruritus that affects so many Alagille patients,” Roberta Smith, president of the Alagille Syndrome Alliance, said in a statement accompanying the approval.1 “I know personally the terrible impact of this rare disease on a child; this approval will help to alleviate the pruritus burden for more patients.”

Odevixibat was previously approved by the FDA to treat pruritus in patients ≥3 months old with progressive familial intrahepatic cholestasis (PFIC).2 It joins fellow IBAT inhibitor maralixibat (LIVMARLI) as the lone treatments approved to treat Alagille syndrome.3

What is Alagille Syndrome?

Alagille syndrome is a genetic disorder in which bile accumulates in the liver, leading to liver damage that may be associated with mortality by age 20 in approximately 25% of all affected patients. It is currently estimated to impact approximately 1 in 70,000 infants. Common symptoms include kidney disease, enlarged spleen, vascular abnormalities, delayed growth, and yellowed, itchy skin.4

Primary odevixibat investigator Nadia Ovchinsky, MD, director of the division of pediatric gastroenterology and hepatology in the department of pediatrics at NYU Grossman School of Medicine, told HCPLive that each child with Alagille syndrome possesses a different phenotype—regardless of any similar genetic mutations.

“It’s a multisystemic disorder, with numerous systems that can be involved: cardiovascular, skeletal, other vascular issues,” Ovchinsky explained.

However, the liver and patients’ “paucity of small intrahepatic bile ducts” remains the key target for care with available therapies, Ovchinsky said. Patients carry a significant risk of developing cholestasis with untreated disease. Supportive care strategies prioritize sufficient nutrition and caloric intake to ensure the children can grow, and symptomatic relief focuses on managing their pruritus.

This is what makes odevixibat and the IBAT inhibitor drug class a particularly promising agent for Alagille syndrome.

How Do IBAT Inhibitors Work?

IBAT inhibitors block the reabsorption of bile acids in the terminal ileum, Kris V. Kowdley, MD, explained to HCPLive last month.5 The director of the Liver Institute Northwest and professor of medicine at Elson S. Floyd College of Medicine at Washington State University described the unique pathway inhibition as a “major advance for at least treating the liver disease in patients with Alagille.”

“The fact we now have data suggesting not only improved outcomes but improved survival in comparison to historical control data is impactful for several reasons,” Kowdley said.

Among the reasons is that he and colleagues can now use increasing real-world evidence to show effect of therapies like the number of IBAT inhibitors in development for Alagille syndrome and other forms of genetic cholestatic syndromes.

Odevixibat Data

Indeed, the once-daily, non-systemic odevixibat was supported by findings from the phase 3 ASSERT trial, in which a 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).6

Ovchinsky and colleagues conducting the ASSERT trial additionally reported significant improvement in mean bile acid count among patients receiving odevixibat versus placebo (P = .0012). As pruritus plays a major hindrance in quality of life—especially for pediatric patients—investigators measured sleep improvement of patients. Those receiving odevixibat reported significant reduction in instances of needing help falling asleep from a parent or guardian versus placebo over 24 weeks (P <.01).

“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 said.7 “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 additionally cited clinician-collected parent and guardian feedback stating improvements in pediatric patients’ sleep and capability to pay attention in the classroom due to reduced itch.

“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.”

In fact, a hopeful tertiary benefit from odevixibat would be a reduction in the Alagille syndrome patient population that needs a liver transplant—an outcome that would be “incredible” for the field, Ovchinsky said.

Kowdley’s optimism for odevixibat and the IBAT inhibitor drug class regarded its effect on patient and parent/guardian livelihood.

“Certainly, it’s less clear whether they’re going to modify disease, but it’s very clear that they have a very dramatic effect on improving quality of life,” he said.


  1. Ipsen. U.S. FDA approves Bylvay® for patients living with cholestatic pruritus due to Alagille syndrome. Press release. Published June 13, 2023. https://www.ipsen.com/press-releases/u-s-fda-approves-bylvay-for-patients-living-with-cholestatic-pruritus-due-to-alagille-syndrome/#:~:text=%E2%80%9CToday's%20approval%20of%20Bylvay%20in,Mayer%2C%20Executive%20Vice%20President%20and
  2. Walter K. FDA Approves Odevixibat for PFIC. HCPLive. Published July 20, 2021. https://www.hcplive.com/view/fda-approves-odevixibat-pfic
  3. Walter K. FDA Approves First Treatment for Rare Pediatric Liver Disease. HCPLive. Published September 29, 2021. https://www.hcplive.com/view/fda-approves-first-treatment-rare-pediatric-liver-disease
  4. Alagille Syndrome. Johns Hopkins Health. Accessed June 13, 2023. https://www.hopkinsmedicine.org/health/conditions-and-diseases/alagille-syndrome
  5. Kunzmann K. Kris Kowdley, MD: IBAT Inhibitors Provide Opportunity Against Alagille Syndrome. HCPLive. Published May 14, 2023. https://www.hcplive.com/view/kris-kowdley-md-ibat-inhibitors-opportunity-alagille-syndrome
  6. 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.
  7. Kunzmann K. Nadia Ovchinsky, MD: Odevixibat's Phase 3 Data and Potential for Alagille Syndrome. HCPLive. Published June 6, 2023. https://www.hcplive.com/view/nadia-ovchinsky-odevixibat-phase-3-data-alagille-syndrome
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