Real-World Odevixibat Data Show Pruritus Relief in Late-Onset PFIC

Adults with late-onset progressive familial intrahepatic cholestasis (PFIC) who received odevixibat (Bylvay) in routine practice reported improved pruritus within 3 months, according to a retrospective case series presented at The Liver Meeting 2026 in Denver, Colorado.¹

Findings also showed that serum bile acids (sBA) and liver enzymes fell during treatment, according to the study abstract.¹

“Findings support potential ODX benefit in this understudied population, although further real-world studies are warranted to strengthen the evidence base and optimize management of late-onset PFIC,” wrote first author Tatyana Kushner, MD, of Weill Cornell Medicine, and colleagues.¹

PFIC is a group of rare autosomal recessive disorders of bile formation. Estimated incidence ranges from 1 in 50,000 to 1 in 100,000 births. The 3 classic types are caused by variants in different hepatocellular transport genes:²

• PFIC1: ATP8B1
• PFIC2: ABCB11, which encodes the bile salt export pump (BSEP)
• PFIC3: ABCB4

PFIC1 and PFIC2 usually appear in the first months of life. PFIC3 can present later in infancy, in childhood, or in young adulthood. Most children develop fibrosis and end-stage liver disease before adulthood and eventually become candidates for liver transplantation.²

Increasing numbers of patients are being diagnosed in adulthood, according to the investigators. These patients often present with heterogeneous, atypical cholestatic phenotypes, and their clinical management remains poorly defined.¹ Last year at the same meeting, Seema Meloni, PhD, and colleagues characterized a cohort of adults with late-onset PFIC identified through electronic health record review at Mayo Clinic and Duke Health. In that cohort, 78.6% of patients had cholestasis, 35.7% had cirrhosis, and 28.6% had pruritus.³ The current analysis focuses on the 3 patients in that cohort who were treated with odevixibat.¹

In July 2021, the US Food and Drug Administration (FDA) approved odevixibat, a nonsystemic ileal bile acid transporter (IBAT) inhibitor, for the treatment of pruritus across all PFIC subtypes. It was the first drug approved for the disease, which before then had only surgical treatment options. Approval followed the phase 3 PEDFIC 1 trial, in which odevixibat met both primary endpoints, for pruritus and sBA, vs placebo.⁴ The US label now covers patients with PFIC aged 3 months or older, as well as cholestatic pruritus in patients with Alagille syndrome aged 12 months or older.⁵ Evidence on clinical outcomes in adults with late-onset disease remains limited.¹

How Did Odevixibat Affect Pruritus and Bile Acids in Late-Onset PFIC?

This noninterventional retrospective study focused on 3 of the 14 adults with late-onset PFIC from the Meloni cohort who were treated with odevixibat at Mayo Clinic or Duke Health.¹,³ Patients were aged 18 years or older, identified by International Classification of Diseases, Ninth Revision (ICD-9) code 576.8 and/or ICD-10 code K76.8, and confirmed by manual chart review. The study period ran from July 20, 2021, through December 31, 2025. Investigators assessed changes in pruritus from unstructured clinical notes, and changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum bile acids (sBA), and alkaline phosphatase (ALP) from structured laboratory fields.¹

Patient characteristics¹:

• Mean (SD) age was 24.3 (9.7) years at the first record of PFIC and 27.0 (11.5) years at odevixibat initiation.
• Mean (SD) observed time on treatment was 12.3 (7.6) months.
• All 3 patients had physician interpretation of genetic testing.
• All 3 had notable hepatocellular injury before treatment, with mean (SD) AST of 113 (76) U/L and ALT of 168.1 (110) U/L.

All 3 patients reported pruritus improvement within 3 months of starting odevixibat, and 1 reported complete resolution of symptoms. Two patients had a temporary treatment interruption. Both restarted odevixibat and again reported pruritus improvement.¹

Of the 2 patients with available sBA data, both had reductions during treatment, of 140 µmol/L and 115 µmol/L, respectively. Mean AST, ALT, and ALP levels also decreased after odevixibat initiation.¹

What Are the Limitations of These Real-World Findings?

The study included only 3 patients and had no comparison group. Pruritus was assessed from clinician notes rather than a validated itch scale, so the size of symptom improvement cannot be quantified. The abstract did not report:

• Posttreatment AST, ALT, or ALP values
• Reasons for the 2 treatment interruptions
• Patients’ specific PFIC genotypes

Genotype is clinically relevant because the odevixibat label notes the drug may not be effective in a subgroup of patients with PFIC2 whose ABCB11 variants result in nonfunctional or absent BSEP protein.⁵

The label also includes warnings for liver test abnormalities, diarrhea, and fat-soluble vitamin deficiency⁵:

• Clinicians should obtain baseline liver tests and monitor closely during the first 6 to 8 months of treatment.
• Odevixibat is contraindicated in patients with prior or current hepatic decompensation.
• The most common adverse reactions in PFIC were liver test abnormalities, diarrhea, abdominal pain, vomiting, and fat-soluble vitamin deficiency.

References

1. Kushner T, Meloni S, Almudallal O, He B, Gomes Da Silva H, Syn WK. Real-world effectiveness of odevixibat in late-onset progressive familial intrahepatic cholestasis (PFIC). Abstract 1294. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis. 2009;4:1. doi:10.1186/1750-1172-4-1
3. Meloni S, et al. Characterization of a cohort of patients with later onset progressive familial intrahepatic cholestasis (PFIC) from two US health systems identified leveraging natural language processing (NLP). Poster 4543. Presented at: The Liver Meeting 2025; November 7-11, 2025; Washington, DC.
4. Albireo Pharma. Albireo announces FDA approval of Bylvay (odevixibat), the first drug treatment for patients with progressive familial intrahepatic cholestasis (PFIC). BioSpace. Published July 20, 2021. Accessed November 5, 2026. https://www.biospace.com/albireo-announces-fda-approval-of-bylvay-odevixibat-the-first-drug-treatment-for-patients-with-progressive-familial-intrahepatic-cholestasis-pfic
5. Bylvay (odevixibat) capsules and oral pellets. Prescribing information. Ipsen Biopharmaceuticals, Inc. Revised March 2025. Accessed November 5, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215498s006lbl.pdf