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WASHINGTON -- Treatment with odevixibat (Bylvay) led to early, rapid, and sustained improvements in pruritus among pediatric patients with Alagille syndrome, as well as reductions in bile acid levels, the phase III trial showed.

In 52 patients with a mean age of 6, those who received odevixibat experienced statistically significant improvements in observer-reported scratching score from baseline to 21-24 weeks compared with placebo (-1.7 vs -0.8, P=0.002), reported Nadia Ovchinsky, MD, MBA, of the Children's Hospital at Montefiore and Albert Einstein College of Medicine in New York City.

Looking at the key secondary endpoint, bile acid levels dropped significantly with odevixibat versus placebo at 20-24 weeks (-90.35 vs 22.39 µmol/L, P=0.001), she said during her late-breaking presentation at the American Association for the Study of Liver Diseases annual meeting.

Furthermore, most sleep parameters improved more with odevixibat than placebo, including days sleeping with caregiver (P=0.003), days needing help to fall asleep (P=0.003), days with soothing (P<0.0001), and tiredness (P=0.012).

"Odevixibat treatment led to significant, rapid, clinically meaningful, and sustained improvements in pruritus, as well as significant reductions in bile acids and improvements in sleep quality," said Ovchinsky.

Andrew Talal, MD, MPH, of the University at Buffalo in New York, told 番茄社区app that "these are encouraging results for a rare disease that has lacked effective treatment."

Alagille syndrome is a life-threatening multisystem disorder caused by JAG1 and NOTCH2 mutations, and often presents as cholestasis with elevated levels of serum bile acids in infancy. Signs that may be linked to cholestasis include severe intractable pruritus, impaired growth, disfiguring xanthomas, and progressive liver disease.

"We're trying to really achieve long-term safety for these patients in order for them to keep their native livers," noted Ovchinsky. "There were some biomarkers that were checked and they will be studied in the secondary analysis."

In July 2021, odevixibat, a selective inhibitor for the ileal bile acid transporter that works to regulate the enterohepatic circulation of bile acids, was approved to treat children ages 3 months and up who have intense itching caused by progressive familial intrahepatic cholestasis, based on results from the PEDFIC 1 trial.

For this multicenter study, Ovchinsky and colleagues randomized 52 patients with Alagille syndrome and significant pruritus, JAG1 (92%) or NOTCH2 (8%) mutations, and elevated serum bile acid levels 2:1 to oral odevixibat 120 µg/kg once daily or placebo for 24 weeks from March 2021 to September 2022.

Of the 35 patients in the odevixibat group, mean age was 6.7, and 40% were girls, while the 17 patients in the placebo group had a mean age of 5.4 and 65% were girls. Nearly all were on concomitant antipruritic medications at baseline. The mean observer-reported pruritus score was 2.8 in the odevixibat group and 3.0 in the placebo group.

Treatment-related adverse events were similar between groups, and mostly mild.

"No patients discontinued this study; in fact, 96% of patients enrolled in the open-label extension trial," Ovchinsky said.

Odevixibat is also currently being evaluated in the ongoing open-label and in the phase III for patients with biliary atresia.

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