Elafibranor Lowers ALP in PBC Patients Switching From Obeticholic Acid

Patients with primary biliary cholangitis (PBC) who switched from obeticholic acid (OCA) to elafibranor had a mean 33% reduction in alkaline phosphatase (ALP) within 6 months, according to a real-world analysis presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee. Patients starting elafibranor as their first second-line therapy had similar improvements in biochemical response.1

Of note, patients treated with OCA within 3 months of enrollment were excluded from ELATIVE, the phase 3 trial supporting elafibranor’s US Food and Drug Administration (FDA) approval, so data on direct switching have been limited.1,2

Limited PBC Treatment Options Before Second-Line PPAR Agonists

For nearly 2 decades, ursodeoxycholic acid (UDCA) was the only approved therapy for PBC, even though up to 40% of patients have an inadequate response. OCA, a farnesoid X receptor agonist, received accelerated approval in 2016 as the first second-line option.

That option has since disappeared. In 2021, the FDA restricted OCA use in patients with advanced cirrhosis after reports of serious liver injury. In September 2025, Intercept Pharmaceuticals voluntarily withdrew OCA from the US market at the FDA’s request, after postmarketing data showed more liver transplants and deaths with OCA than with placebo.3

FDA Approvals of Elafibranor and Seladelpar for PBC

A pair of peroxisome proliferator-activated receptor (PPAR) agonists received FDA accelerated approval in 2024 for patients with an inadequate response to, or intolerance of, UDCA. Elafibranor (Iqirvo), a dual PPARα/δ agonist, was approved in June 2024. Seladelpar (Livdelzi), a selective PPARδ agonist, followed in August 2024.4

In ELATIVE, 51% of patients receiving elafibranor achieved a biochemical response at week 52, compared with 4% of those receiving placebo. ALP normalized in 15% of elafibranor-treated patients and in none of the placebo group.2

Real-World Elafibranor Study Design and Patient Cohorts

Channa Jayasekera, MD, of the Mayo Clinic Arizona, and colleagues analyzed US HealthVerity network data from January 2024 to January 2026. Eligible adults with PBC received ≥ 1 dose of elafibranor and had follow-up ALP data.1

Cohort 1 included patients who switched from OCA to elafibranor within 3 months and had no other second-line therapy. Cohort 2 included patients who started elafibranor, alone or with UDCA, without prior second-line treatment. Of 59 switchers and 305 elafibranor-only patients, 14 and 108, respectively, met the full inclusion criteria.1

Median elafibranor treatment duration was 171.5 days in Cohort 1 and 160.5 days in Cohort 2. In Cohort 1, median OCA duration was 242.0 days, and the median gap before starting elafibranor was 26.0 days.1

ALP Reductions and Biochemical Response After Switching to Elafibranor

From pre-index to the 6-month post-index average, mean ALP fell by 71.8 U/L (−33.1%) in Cohort 1 and by 54.5 U/L (−21.2%) in Cohort 2. The proportion with ALP below 1.67 times the upper limit of normal rose from 71.4% to 92.9% in Cohort 1 and from 66.7% to 86.1% in Cohort 2.1

ALP newly normalized after starting elafibranor in 50.0% of Cohort 1 and 49.4% of Cohort 2. Alanine aminotransferase and aspartate aminotransferase stayed broadly stable in both cohorts.1

References

1. Jayasekera CR, Bowlus CL, Meloni S, et al. Elafibranor is effective in real-world settings in patients with primary biliary cholangitis who switched treatment from obeticholic acid. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.

2. Kowdley KV, Bowlus CL, Levy C, et al. Efficacy and safety of elafibranor in primary biliary cholangitis. N Engl J Med. 2024;390(9):795-805. doi:10.1056/NEJMoa2306185

3. Brooks A. Intercept Voluntarily Withdraws Obeticholic Acid (Ocaliva) for PBC From US Market. HCPLive. September 11, 2025. Accessed October 15, 2026. https://www.hcplive.com/view/intercept-voluntarily-withdrawals-obeticholic-acid-ocaliva-for-pbc-from-us-market

4. Gilead’s Livdelzi (seladelpar) granted accelerated approval for primary biliary cholangitis by US FDA. News release. Gilead Sciences. August 14, 2024. Accessed October 15, 2026. https://www.gilead.com/news/news-details/2024/gileads-livdelzi-seladelpar-granted-accelerated-approval-for-primary-biliary-cholangitis-by-us-fda