The US Food and Drug Administration (FDA) has expanded the indication for odevixibat (Bylvay) to include treatment of cholestatic pruritus associated with Alagille syndrome (ALGS) in patients as young as 12 months.

ALGS is a rare inherited disorder in which bile builds up in the liver because there are too few bile ducts to drain the bile, causing liver damage. ALGS can also affect multiple organ systems, including the heart, skeleton, eyes, and kidneys. Nearly all patients with the condition present with chronic cholestasis, usually within the first few months of life, and as many as 88% also present with severe, intractable pruritus.

Odevixibat is a potent, nonsystemic ileal bile acid transport inhibitor. The FDA approved the drug in 2021 for patients with cholestatic pruritus due to progressive familial intrahepatic cholestasis.

The FDA nod for odevixibat in ALGS was based on results of the phase 3 ASSERT study, which evaluated the safety and efficacy of 120 µg/kg/day odevixibat for 24 weeks in relieving pruritus in infants, children, and adolescents from birth to age 17 years with genetically-confirmed ALGS. The study was conducted at 32 sites across North America, Europe, Middle East, and Asia Pacific.

The study met the primary endpoint showing highly statistically significant and clinically meaningful sustained improvement in pruritus, starting early after initiation of treatment, compared with placebo (P = .002), the drug’s manufacturer, Ipsen Pharmaceuticals, said today in a news release.

More than 90% of patients were pruritus responders (≥ 1 point change at any time during 24 weeks).

The study also met the key secondary endpoint showing a highly statistically significant reduction in serum bile acid concentration from baseline to the average of weeks 20 and 24, compared with placebo (P = .001).

Odevixibat treatment also led to statistically significant improvements in multiple sleep parameters as early as the first week with continued improvement through week 24.

The overall incidence of treatment-emergent adverse events was similar to placebo. No patients left the study, and 96% of patients rolled over into the open-label extension study.

The most common adverse reactions seen in patients with ALGS are diarrhea, abdominal pain, hematoma, and weight loss.

“Physicians urgently need more options to treat patients with Alagille syndrome and this approval from the US FDA spotlights the robustness of the phase 3 ASSERT clinical study results,” principal investigator Nadia Ovchinsky, MD, chief, Division of Gastroenterology and Hepatology, Hassenfeld Children’s Hospital at NYU Langone, said in the release.

“The ASSERT study showed that Bylvay reduced pruritus associated with ALGS, which is so common among this patient population and one of the leading indications for a liver transplant,” said Ovchinsky.

Roberta Smith, president of the Alagille Syndrome Alliance, said, “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.”

“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,” added Smith.

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