Elafibranor Shows No Impact on Renal Function in Primary Biliary Cholangitis Patients
核心洞察
A secondary analysis of the phase 3 ELATIVE trial indicates that elafibranor treatment does not adversely affect renal function markers in patients with primary biliary cholangitis (搜索) (PBC (搜索)).
The study found that median levels of renal parameters remained stable in both elafibranor and placebo groups over 52 weeks.
Acute kidney injury was infrequent, with no clinically meaningful changes in renal function observed during the trial.
Elafibranor (Iqirvo) treatment for primary biliary cholangitis (搜索) (PBC (搜索)) does not negatively impact renal function, according to a secondary analysis of the phase 3 ELATIVE study presented at The Liver Meeting 2024. The research, led by Marcelo Kugelmas, MD, suggests that the peroxisome proliferator-activated receptor (搜索) (PPAR (搜索))-α/δ agonist is not associated with renal dysfunction in PBC patients.
ELATIVE Trial Details
The ELATIVE trial, a multi-center, randomized, double-blind, placebo-controlled phase 3 study, led to the FDA's accelerated approval of elafibranor on June 10, 2024. The approval was based on a significant reduction in alkaline phosphatase (ALP) levels. The primary endpoint of biochemical response was achieved in 51% of patients treated with elafibranor 80 mg plus UDCA (n = 108) compared to 4% in the placebo plus UDCA group (n = 53). Additionally, 15% of elafibranor-treated patients achieved normalization in ALP levels versus 0% in the placebo group.
Renal Function Analysis
The secondary analysis assessed cystatin C (CysC) and serum creatinine (SCr) levels over 52 weeks. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations. Patients with pre-existing renal impairment (eGFR <60 mL/min/1.73 m2) were excluded from the study.
Key Findings
Among the 161 patients randomized to elafibranor (n = 108) or placebo (n = 53), median levels of renal parameters were similar at baseline and remained stable through week 52. The median changes from baseline at week 52 in CysC were 0.00% in the elafibranor group and 3.54% in the placebo group. Changes in SCr were 0.010 mg/dL and -0.009 mg/dL, respectively. Median eGFR remained stable in both groups, with similar changes from baseline in CysC-based eGFR between the elafibranor (0.00 mL/min/1.73 m2) and placebo (-3.40 mL/min/1.73 m2) groups. No association was found between changes in CysC-based eGFR and corresponding changes in SCr and eGFR.
Safety Profile
Acute kidney injury was reported in 3 (2.8%) patients receiving elafibranor and 1 (1.9%) receiving placebo. Notably, 2 out of the 3 elafibranor-treated patients with acute kidney injury had type 2 diabetes.
Expert Commentary
"We can say that there was no clinically meaningful change in renal function, and at 52 weeks of therapy, there was no safety signal for any potential renal toxicity for use in of this particular compound in this particular population," Kugelmas concluded.