Elafibranor vs Seladelpar in PBC: No Clear 1-Year Advantage

Elafibranor and seladelpar showed no statistically significant differences in 1-year liver outcomes, hospitalization, cardiovascular events, or alkaline phosphatase (ALP) levels in a propensity-matched study of adults with primary biliary cholangitis (PBC) receiving ursodeoxycholic acid (UDCA). The findings were presented at The Liver Meeting 2026 in Denver.¹

Mohammad Alabbas, MD, a research fellow in the hepatology section of the gastrointestinal department at Cleveland Clinic, discussed the comparison in an interview with HCP Live. The clinical question was whether real-world evidence could distinguish between these second-line treatment options.

Investigators used the TriNetX Research Network, encompassing 111 health systems, to identify UDCA-treated adults initiating either agent. Patients with competing liver diseases were excluded. After propensity-score matching, each group included 238 patients. Outcomes were assessed through 365 days after treatment initiation.¹

The primary composite of major adverse liver outcomes occurred in 12.6% of elafibranor users versus 15.5% of seladelpar users (hazard ratio, 0.82; 95% CI, 0.51-1.33). All-cause hospitalization occurred in 5.5% versus 5.0%, respectively. Neither difference was statistically significant.¹

Among patients with available follow-up testing, mean ALP was 162.7 U/L with elafibranor versus 175.1 U/L with seladelpar (P = .324). Cardiovascular events and low albumin also did not differ significantly.¹

Separate phase 3 trials, ELATIVE (NCT04526665) and RESPONSE (NCT04620733), previously demonstrated greater biochemical response with elafibranor and seladelpar, respectively, versus placebo; neither directly compared the agents.²˒³

In discussing the database approach, Alabbas highlighted its value for studying a rare disease across multiple institutions. He also identified potential diagnostic misclassification, selection bias, and limitations in verifying underlying electronic health record data.

The findings did not establish equivalence or superiority. For physicians considering second-line therapy, the study leaves comparative treatment selection unresolved and supports larger studies with longer clinical follow-up and validated biochemical response definitions to better assess differences in clinical outcomes and guide individualized treatment decisions.

References

1. Alabbas M, Eren B, Sims O, Chiang D. Elafibranor versus seladelpar in UDCA-treated primary biliary cholangitis: a 111-health-system propensity-matched comparative effectiveness study. Presented at: The Liver Meeting 2026; Denver, CO.
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. Hirschfield GM, Bowlus CL, Mayo MJ, et al. A phase 3 trial of seladelpar in primary biliary cholangitis. N Engl J Med. 2024;390(9):783-794. doi:10.1056/NEJMoa2312100