Elafibranor improves biochemical response and favorably modifies GLOBE and UK-PBC prognostic scores in primary biliary cholangitis: analyses from the phase III ELATIVE® trial

Background Elafibranor demonstrated significant biochemical response in patients with primary biliary cholangitis (PBC) in the phase III ELATIVE ® trial. Biochemical response can be defined using various criteria, and prognostic tools such as GLOBE and UK-PBC predict estimated transplant-free survival and mortality. Here, we assess the efficacy of elafibranor across different biochemical response criteria and prognostic scores. Methods Using Week 52 data from ELATIVE ® , biochemical response was analyzed according to Paris I, Paris II, Barcelona, Toronto, Momah/Lindor, deep biochemical response, and complete biochemical response criteria. GLOBE and UK-PBC scores were calculated at baseline through Week 52; risk scores at baseline and Week 52 were used to estimate transplant-free survival rates at 5, 10, and 15 years, and were analyzed in subgroups of patients according to achievement of biochemical response. Results Responder rates at Week 52 favored elafibranor over placebo across all criteria: Paris I (68.9% versus 47.2%), Paris II (43.0% versus 5.7%), Barcelona (54.7% versus 0%), Toronto (51.9% versus 9.4%), Momah/Lindor (51.9% versus 9.4%), deep biochemical response (14.2% versus 0%), and complete biochemical response (9.3% versus 0%). Based on GLOBE and UK-PBC scores at Week 52, patients receiving elafibranor had higher median estimated transplant-free survival versus placebo at 15 years (87.1% versus 82.0%; 96.7% versus 95.1%, respectively). Reductions in predicted GLOBE risk scores were seen in patients receiving elafibranor regardless of whether they had achieved biochemical response according to different criteria. Conclusions Irrespective of the criteria used, 52 weeks of elafibranor treatment resulted in consistently higher rates of biochemical response compared with placebo in patients with PBC. Predicted improvements in transplant-free survival, as assessed by two prognostic scores, corroborate these observations, and estimated reductions in liver transplant risk were seen independent of achievement of biochemical response, supporting broad efficacy of elafibranor. Trial registration Available at: https://clinicaltrials.gov/study/NCT04526665 Trial registration number: NCT04526665. Study registration date (first posted): 26/08/2020.