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Odevixibat (Bylvay) reduced intense itching and serum bile acids in children with progressive familial intrahepatic cholestasis (PFIC), as detailed in the publication of the PEDFIC 1 trial results that led to the drug's recent FDA approval.

Among 62 outpatients with PFIC, a model-adjusted analysis showed that those who received one of two daily odevixibat doses had significantly more positive pruritus assessments (PPAs) from caregivers -- a scratching score of 1 or less, or at least a 1-point decline -- compared to placebo over the 24-week study period (P=0.0038):

• Odevixibat 40 μg/kg: 58% vs 30%
• Odevixibat 120 μg/kg: 52% vs 30%
• Both doses combined: 55% vs 30%

And significantly more achieved serum bile acid response with odevixibat as well (43%, 21%, 33%, respectively, vs 0% with placebo), reported Richard Thompson, MD, PhD, of the King's College Hospital in London, and colleagues, writing in .

These results "represent the potential for a paradigm shift" in treatment, said Thompson in a when results of the trial were first announced. "Coupled with the favorable safety and tolerability profile odevixibat exhibited, these data underscore the potential to improve upon the current standard of care, which typically consists of off-label medications or invasive surgeries including transplant."

PFIC comprises a group of genetic liver diseases in children that develop from mutations that affect bile secretion, Thompson's group noted. Bile acid retention occurs with PFIC and can lead to cirrhosis, hepatocellular carcinoma, and end-stage liver disease.

In July 2021, the ileal bile acid transporter inhibitor, odevixibat, became the first FDA approved therapy to treat the rare liver disease, targeting pruritus in all PFIC subtypes for ages 3 months and up, based on results from the PEDFIC 1 trial.

Still, odevixibat doesn't appear to be a silver bullet for the disease.

For example, it "works for patients who have residual ABCB11 function, but not for those with biallelic loss of function in ABCB11 and advanced cirrhosis," Huey-Ling Chen, MD, PhD, and Shu-Hao Hsu, PhD, both of the National Taiwan University College of Medicine in Taipei, stated in an . "Liver transplantation is probably the option for these patients at any age when indicated."

Early diagnosis and timely medical therapy are important to avoid running out of therapeutic options, they noted, although other classes of medication are in development for cholestatic liver diseases.

From 2018 to 2020, Thompson and colleagues enrolled 62 pediatric outpatients with PFIC type 1 or 2, who had pruritus and elevated baseline serum bile acids, across 33 global sites. Participants were randomized 1:1:1 to receive a once-daily, double-blind oral dose of 40 μg/kg or 120 μg/kg of odevixibat or placebo for 24 weeks. Researchers stratified participants based on PFIC type and age. The trial included participants ages 0.5 to 18 years from the U.S., Canada, Europe, Australia, and the Middle East.

Excluded were those with other forms of liver disease, inflammatory bowel disease, chronic diarrhea, chronic infection, chronic kidney disease, two mutations in ABCB11 "predicting a complete absence of functional bile salt export pump," and those who underwent liver transplantation, among others.

Pruritus was assessed by caregivers with the sponsor Albireo's observer-reported outcome PRUCISION instrument in an electronic diary. Serum bile acid response, measured by fasting blood samples, was defined by a reduction of ≥70% from baseline or ≤70 μmol/L concentrations at 24 weeks.

Participants could continue in the open-label ongoing extension study, , with results spanning 72 weeks.

Median age was 3 years and participants were evenly divided between girls and boys. Most patients were white (83-85%), and nearly three-fourths had PFIC type 2. Most were on ursodeoxycholic acid (81%) or rifampicin (66%) at baseline. At baseline, average serum bile acids were 221-255 μmol/L, and the average pruritus score was 3.

The two odevixibat doses had similar safety profiles. Treatment-emergent adverse events (TEAEs) more common in the odevixibat groups included diarrhea/frequent bowel movements (31% vs 10% with placebo) and fever (29% vs 25%). Serious TEAEs occurred more frequently with placebo (25%) than with odevixibat (7%). No deaths occurred.

"Drug-related treatment-emergent adverse events, including gastrointestinal symptoms, elevated alanine aminotransferase or serum bilirubin, were mostly mild or moderate and occurred in around a third of patients," the editorialists noted. "The drug is well-tolerated in most patients."

The authors acknowledged that their findings may not be generalizable to all PFIC patients.

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