Elafibranor Improves Predicted Transplant-Free Survival Based on GLOBE, UK-PBC Scores

Kris Kowdley, MD

Credit: Velocity Clinical Research

Treatment with elafibranor (Iqirvo) for primary biliary cholangitis (PBC) is associated with improvements in predicted transplant-free survival based on GLOBE and UK-PBC scores as early as week 4, according to findings from a recent study.¹

The research was presented at The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD) in San Diego, California, by Kris Kowdley, MD, director of Liver Institute Northwest, and showed further improvements in both scores were observed through 52 weeks of treatment in the phase 3 ELATIVE study.¹

Elafibranor was granted accelerated approval for the second-line treatment of PBC on June 10, 2024, making it just the second second-line therapy to receive FDA approval at the time. The dual peroxisome proliferator-activated receptor (PPAR)-α/δ agonist’s accelerated approval was supported by a reduction of alkaline phosphatase (ALP) observed in the multi-center, randomized, double-blind, placebo-controlled phase 3 ELATIVE trial evaluating the efficacy and safety of elafibranor versus placebo for the treatment of patients with PBC with an inadequate response or intolerance to ursodeoxycholic acid.²

In the trial, patients were randomly assigned in a 2:1 ratio to once-daily elafibranor 80 mg (n = 108) or placebo (n = 53) for 52 weeks. GLOBE and UK-PBC scores were analyzed at baseline and again at weeks 4, 13, 26, 39, and 52 of the study. Both are validated prognostic scores for estimating the risk of liver transplant or death after 1 year of UDCA therapy and have been used to evaluate the benefit of other second-line agents, such as obeticholic acid. They are based on levels of ALP, total bilirubin (TB), aspartate transaminase (AST), alanine transaminase (ALT), albumin, and platelets.¹

Among the ELATIVE cohort, the mean age was 57 (standard deviation [SD], 9) years and the majority (96%) of patients were female. Mean baseline values were 321.9 (SD, 150.9) U/L for ALP; 9.6 (5.1) μmol/L for TB; 45.7 (27.2) U/L for AST; 49.6 (32.6) U/L for ALT; 43.8 (3.0) g/L for albumin; and 263.6 (76.8) ×109/L for platelets.1At baseline, investigators noted the mean GLOBE and UK-PBC scores were −0.63 (SD, 0.67) and −0.74 (SD, 0.90) in the elafibranor group compared with −0.73 (SD, 0.73) and −0.80 (SD, 0.86) in the placebo group, respectively. After 1 year of treatment, the mean change from baseline in GLOBE and UK-PBC scores were −0.36 (SD, 0.40) and −0.27 (SD, 0.53) in the elafibranor group compared with 0.13 (SD, 0.45) and 0.05 (SD, 0.63) in the placebo group, respectively.¹

Investigators additionally pointed out changes in both scores were seen after 4 weeks and continued through 52 weeks of treatment, primarily driven by reductions in ALP.1Further analysis of GLOBE scores at week 52 showed the median estimated transplant-free survival rates at 5, 10, and 15 years were 97.78%, 94.12%, and 89.71% in the elafibranor group, compared with 97.19%, 92.62%, and 87.15% in the placebo group. Based on UK-PBC scores at week 52, the median estimated transplant-free survival rates at 5, 10, and 15 years were 99.46%, 98.19%, and 96.65% in the elafibranor group, compared with 99.20%, 97.35%, and 95.12% in the placebo group.¹

References

1. ^{Kowdley K, Lawitz E, Spearman C, et al. One-year treatment with elafibranor in the phase III ELATIVE trial improves GLOBE and UK-PBC prognostic scores. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.}
2. ^{Brooks, A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed November 16, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc}