Elafibranor Sustains Biochemical Response Across PBC Stages Through 4 Years

Elafibranor (Iqirvo) maintained improvements in markers of disease activity in patients with primary biliary cholangitis (PBC) with either early or advanced stage disease for up to 4 years, according to data from the open-label extension (OLE) of the phase 3 ELATIVE trial presented at AASLD The Liver Meeting 2026.¹ Biochemical response rates were numerically lower among patients with advanced disease, but noninvasive tests (NITs) of fibrosis remained stable in both groups.¹

Marlyn Mayo, MD, of UT Southwestern Medical Center, presented the findings and discussed the data in an interview with HCPLive. She noted patients with advanced disease are the ones clinicians most want to help, yet they remain the least represented in clinical trials, leaving long-term subgroup analyses as an important source of evidence.

How Did Elafibranor Perform in Early vs Advanced Stage PBC?

The present analysis included patients who completed the ELATIVE double-blind period and continued elafibranor 80 mg into the OLE (continuous patients) or switched from placebo to elafibranor (crossover patients). Disease stage was categorized as early or advanced by liver stiffness measurement (LSM; ≤10 or >10 kPa) or, among patients with a biopsy, by Nakanuma fibrosis score (<2 or ≥2). Among continuous patients, 73 had early and 35 had advanced stage disease at baseline, compared with 31 and 14 among crossover patients.¹

Patients with advanced disease had greater mean baseline alkaline phosphatase (ALP) levels (continuous patients: 351.9 [SD, 109.1] U/L vs 306.6 [SD, 125.7] U/L).¹ At Week 156, biochemical response occurred in 73.1% of continuous patients with early stage disease vs 52.4% with advanced stage disease, while ALP normalization occurred in 28.9% versus 23.8%, respectively.¹

Among crossover patients, 60.0% with early stage and 37.5% with advanced stage disease achieved biochemical response at Week 104, and 24.0% versus 25.0% achieved ALP normalization. Through Week 208, continuous patients across disease stages had reductions in ALP and alanine aminotransferase, while total bilirubin and aspartate aminotransferase remained stable.¹

According to Mayo, patients with advanced disease showed a robust response worth pursuing, even if not quite as strong as in earlier stages. She emphasized durability as the central message, given evidence patients with PBC on ursodiol can maintain a biochemical response for years before breaking through, with breakthrough tied to worse outcomes.

“You can have good biochemical response for years, and then at some point you break through... So the durability is very important,” Mayo said.

Do Fibrosis Markers Change With Long-Term Elafibranor?

In a pooled analysis of continuous and crossover patients, mean enhanced liver fibrosis (ELF) scores, LSM, and PRO-C3 values remained stable in both early and advanced stage groups through 156 weeks of elafibranor exposure.¹ Elafibranor was well tolerated across disease stages, with safety findings reported through Week 208. The authors concluded elafibranor provided a consistent treatment effect regardless of disease stage, with stabilization or improvement in disease activity markers and NITs of fibrosis.¹

Mayo described the fibrosis findings as among the most notable aspects of the poster. Earlier analyses showed little change in fibrosis markers, and investigators had attributed this to short follow-up. At 4 years, she said, downward trends in liver stiffness and other fibrosis markers are beginning to emerge, particularly among patients with advanced fibrosis at baseline.

“The patients who have the most fibrosis to start with are the ones in which you can see the improvement in fibrosis best,” Mayo said.

Mayo cautioned key questions remain unanswered, including whether elafibranor will significantly improve liver stiffness and prevent decompensation events such as variceal bleeding, ascites, encephalopathy, or the need for transplant.

Elafibranor received accelerated approval from the US Food and Drug Administration in June 2024 for PBC in combination with ursodeoxycholic acid in adults with an inadequate response, or as monotherapy in those unable to tolerate it, based on the ELATIVE trial.²

References:

1. Mayo M, Kowdley K, Bowlus C, et al. Elafibranor improves markers of disease activity in primary biliary cholangitis across disease stages in patients with up to 4 years of treatment. Presented at: The Liver Meeting 2026; November 5-9, 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