Odevixibat Significantly Benefits Pediatric PFIC Regardless of Patient Subtype


Data from the phase 3 PEDFIC trial program show the IBAT inhibitor benefits bile acid levels as well as itch and sleep issues among children with varying types of PFIC.

Odevixibat Significantly Benefits Pediatric PFIC Regardless of Patient Subtype

Piotr Czubkowski, PhD

Credit: ESGHAN

Odevixibat was associated with decreased serum bile acid as well as improved pruritus in treated patients with varying subtypes progressive familial intrahepatic cholestasis (PFIC), according to paired data from a phase 3 clinical trial and its open-label extension study.

In research from the PEDFIC 1 and 2 trials, a multinational team of investigators reported the ileal bile acid transporter (IBAT) inhibitor odevixibat provided significant benefit across symptomatic and laboratory measures of PFIC—including improved measures of patient sleep and quality of life (QoL). The findings contribute to a growing portfolio of clinical benefit associated with odevixibat across numerous cholestatic conditions.

Presented in an abstract at the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) 2023 Annual Meeting in San Diego this week, the pooled analysis sought to assess odevixibat treatment outcomes across subgroups of patients with PFIC. Led by Piotr Czubkowski, PhD, of the department of gastroenterology, hepatology, nutritional disorders, and pediatrics at the Children’s Memorial Health Institute in Warsaw, Poland, investigators were interested in potential treatment efficacy disparities across the clinical subtypes of PFIC patients in PEDFIC 1 and 2.

“Although symptoms may vary by PFIC type, shared clinical features can include elevated serum bile acids, progressive liver damage, and intractable pruritus that may impact sleep and QoL,” they wrote. “In the phase 3 PEDFIC 1 and PEDFIC 2 studies in patients with PFIC, key outcomes were related to the effects of odevixibat, an ileal bile acid transporter inhibitor, on serum bile acids, pruritus, and safety; sleep and QoL were evaluated as additional efficacy endpoints.”

The 24-week PEDFIC trial randomized pediatric patients with either PFIC type 1 or 2 to odevixibat or placebo, while the ongoing PEDFIC 2 open-label extension included either PEDFIC 1 completed participants or newly enrolled patients with any PFIC subtype. Czubkowski and colleagues analyzed data available from first dose of odevixibat to a data cutoff point of July 2022.

Outcomes included serum bile acid measures; caregiver-rated scores for patient pruritus and tiredness via PRUCISION, a 0-4 scale with higher scores indicating worse symptoms; the caregiver-rated Pediatric QoL Inventory (PedsQL) and family impact (FI) questionnaires—each 0-100 scales with higher scores indicating better QoL. The team also reported treatment-emergent adverse events (TEAEs).

The pooled population included 119 patients. Mean age was 5.9 years old; disease subtypes were as follows:

  • 35 patients with PFIC type 1 (mean odevixibat treatment, 93 weeks)
  • 72 patients with PFIC type 2 (mean odevixibat treatment, 82 weeks)
  • 7 patients with PFIC type 3 (mean odevixibat treatment, 80 weeks)
  • 2 patients with a MYO5B deficiency (mean odevixibat treatment, 107 weeks)
  • 2 patients with a TJP2 deficiency (mean odevixibat treatment, 10 weeks)
  • 2 patients with recurrent episodic cholestasis (mean odevixibat treatment, 7 weeks)

Across all patient populations, mean baseline serum bile acid levels were 241 μmol/L; mean PRUCISION scores were 2.9 at baseline. Investigators observed a mean change of –108 μmol/L in serum bile acid levels from baseline to weeks 70 - 72; mean pruritus scores changed by -1.4from baseline to weeks 61 - 72. Patients with PFIC type 2 reported the greatest reduction in mean bile acid; patients with type 1 or 3 reported the greatest improvement in PRUCISION scores.

Mean tiredness scores were 2.4 overall at baseline; mean change was -1.2 by weeks 61 - 72. Patients additionally reduced their rate of days needing help falling asleep from 74% at baseline to 32% by weeks 61 - 72.

Investigators additionally observed improved PedsQL and FI total scores from 57 and 61, respectively, at baseline to 73 and 68, respectively, at week 72.

More than 9 in 10 patients (n = 108 [91%]) reported TEAEs, with the most common being pyrexia (n = 36) and diarrhea (n = 28).

“In the PEDFIC 1 and PEDFIC 2 studies, decreases in serum bile acids and/or improvements in pruritus scores were observed with odevixibat in patients with PFIC, across all PFIC types represented in the studies, although the magnitude of efficacy response was variable in some subgroups,”investigators concluded. “Odevixibat treatment also resulted in mean improvements in sleep parameters and QoL. TEAEs with odevixibat in this pooled analysis were consistent with previously reported results.”


  1. Czubkowski P, Dalgic B, Lainka E, Ozen H, et al. Changes in Serum Bile Acids, Pruritus, Sleep, and Quality of Life with Odevixibat: Results by Progressive Familial Intrahepatic Cholestasis Type. Paper presented at: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition 2023 Annual Meeting; October 4 - 7; San Diego, CA. Accessed October 6, 2023.
  2. 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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