Elafibranor Bests Obeticholic Acid for ALP Normalization in PBC

Patients with primary biliary cholangitis (PBC) who started elafibranor were significantly more likely to reach complete alkaline phosphatase (ALP) normalization than those who started obeticholic acid (OCA), according to a propensity-matched, real-world analysis presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee.¹

Lowering ALP is a central goal for patients with an inadequate response to first-line ursodeoxycholic acid (UDCA), since biochemical response is closely tied to disease progression. Until now, no direct comparison of real-world normalization rates between the 2 second-line agents had been available, according to the investigators.¹

A Shifting Second-Line Treatment Landscape in PBC

For nearly 2 decades, UDCA was the only approved treatment for PBC, leaving patients with an incomplete response few alternatives. OCA, a farnesoid X receptor agonist, received accelerated approval in 2016 and became the main second-line option.

Safety concerns later narrowed its use. The FDA restricted OCA in patients with advanced cirrhosis in 2021. 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

A pair of peroxisome proliferator-activated receptor (PPAR) agonists have filled the gap. Elafibranor (Iqirvo), a dual PPARα/δ agonist, received accelerated approval in June 2024, followed by the selective PPARδ agonist seladelpar (Livdelzi) in August 2024.⁴ In the phase 3 ELATIVE trial, 51% of elafibranor-treated patients achieved a biochemical response at 52 weeks vs 4% of those on placebo, and 15% achieved ALP normalization.²

TriNetX Propensity-Matched Study Design

Adalberto Guzman, MD, of the University of Arkansas for Medical Sciences, and colleagues used the TriNetX Global Collaborative Network to identify adults aged 18 to 90 years with PBC newly started on OCA or elafibranor.¹ Cohorts were propensity matched 1:1 for demographics, digestive comorbidities, and baseline ALP.

The primary outcome was complete ALP normalization, defined as ALP ≤ 120 U/L during follow-up. Matching produced 2 balanced cohorts of 444 patients each, with a mean age of about 61 years, more than 92% women, and a mean baseline ALP of 295 U/L.¹

Elafibranor Linked to Higher ALP Normalization Rates

Overall, 23.4% (n = 104) of patients on elafibranor reached complete ALP normalization, compared with 14.6% (n = 65) of patients on OCA. The risk difference was 8.8 percentage points in favor of elafibranor (95% CI, 3.7-13.9; P = .0009).¹

Patients receiving OCA had a 37.5% lower likelihood of reaching the target (risk ratio, 0.625; 95% CI, 0.472-0.827). The odds ratio was 0.561 (95% CI, 0.398-0.790).¹

Median follow-up was 207 days for elafibranor and 365 days for OCA. The investigators suggested elafibranor’s higher normalization rate over a shorter window may reflect a more rapid therapeutic effect, and concluded it may be a preferred second-line option when complete biochemical normalization is the goal.¹

References

1. Guzman A, Modi P, Kolluru S, et al. Comparative real-world likelihood of complete alkaline phosphatase normalization with obeticholic acid versus elafibranor in primary biliary cholangitis. 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 16, 2026. https://www.gilead.com/news/news-details/2024/gileads-livdelzi-seladelpar-granted-accelerated-approval-for-primary-biliary-cholangitis-by-us-fda