Elafibranor Demonstrates Improved Transplant-Free Survival in PBC Patients
核心洞察
Elafibranor (Iqirvo) shows early improvements in predicted transplant-free survival for primary biliary cholangitis (搜索) (PBC (搜索)) patients based on GLOBE and UK-PBC scores.
The Phase 3 ELATIVE study data presented at The Liver Meeting 2024 indicates improvements as early as week 4, sustained through 52 weeks of treatment.
The improvements are primarily driven by reductions in alkaline phosphatase (ALP) levels, a key marker in PBC (搜索) prognosis.
Elafibranor (Iqirvo) treatment for primary biliary cholangitis (搜索) (PBC (搜索)) is associated with improved predicted transplant-free survival, according to the GLOBE and UK-PBC scores. The findings, presented by Kris Kowdley, MD, at The Liver Meeting 2024, highlight the potential benefits of elafibranor in managing PBC. The Phase 3 ELATIVE study demonstrated that these improvements were observed as early as week 4 and sustained through 52 weeks of treatment.
The accelerated approval of elafibranor by the FDA on June 10, 2024, marks it as the second second-line therapy for PBC (搜索) at the time. This dual peroxisome proliferator-activated receptor (PPAR (搜索))-α/δ agonist's approval was based on the reduction of alkaline phosphatase (ALP) levels seen in the ELATIVE trial. This multi-center, randomized, double-blind, placebo-controlled trial evaluated elafibranor versus placebo in PBC patients with an inadequate response or intolerance to ursodeoxycholic acid.
The ELATIVE trial randomized patients in a 2:1 ratio to either once-daily elafibranor 80 mg (n = 108) or placebo (n = 53) for 52 weeks. The GLOBE and UK-PBC (搜索) scores, validated prognostic tools for estimating liver transplant or death risk after one year of UDCA therapy, were analyzed at baseline and at weeks 4, 13, 26, 39, and 52. These scores incorporate levels of ALP, total bilirubin (TB), aspartate transaminase (AST), alanine transaminase (ALT), albumin, and platelets.
Baseline Characteristics and Score Changes
The ELATIVE cohort had a mean age of 57 (SD, 9) years, with 96% being female. Baseline values included a mean ALP of 321.9 (SD, 150.9) U/L, TB of 9.6 (5.1) μmol/L, AST of 45.7 (27.2) U/L, ALT of 49.6 (32.6) U/L, albumin of 43.8 (3.0) g/L, and platelets of 263.6 (76.8) ×109/L. The mean baseline GLOBE and UK-PBC (搜索) scores were -0.63 (SD, 0.67) and -0.74 (SD, 0.90) in the elafibranor group, respectively, compared to -0.73 (SD, 0.73) and -0.80 (SD, 0.86) in the placebo group. After one year, 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 to 0.13 (SD, 0.45) and 0.05 (SD, 0.63) in the placebo group.
Impact on Transplant-Free Survival
Changes in both scores were observed after 4 weeks and continued through 52 weeks, primarily driven by ALP reductions. Further analysis of GLOBE scores at week 52 showed 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 to 97.19%, 92.62%, and 87.15% in the placebo group. Based on UK-PBC (搜索) 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 to 99.20%, 97.35%, and 95.12% in the placebo group.