Marcelo Kugelmas, MD: Elafibranor (Iqirvo) Does Not Impact Renal Function in PBC

Treatment with elafibranor (Iqirvo) for primary biliary cholangitis (PBC) does not impact markers of renal function, according to findings from a secondary analysis of the phase 3 ELATIVE 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 Marcelo Kugelmas, MD, director of hepatology and research at South Denver Gastroenterology, and shows use of the peroxisome proliferator‑activated receptor (PPAR)-α/δ agonist for the treatment of PBC is not associated with renal dysfunction.¹

“Some PPAR-type drugs have been shown to have renal dysfunction in their use, so the idea was to try to figure out if the use of this particular PPAR agonist would have a safety signal in the renal arena when used for the duration of this particular trial,” Kugelmas explained to HCPLive.

Elafibranor was granted accelerated approval by the US Food and Drug Administration on June 10, 2024, based on a reduction in alkaline phosphatase observed in the multi-center, randomized, double-blind, placebo-controlled phase 3 ELATIVE trial. Results showed 13 times more patients achieved the composite primary endpoint of biochemical response when treated with elafibranor 80 mg plus UDCA (n = 108) versus placebo plus UDCA (n = 53) (51% vs 4%). Secondary endpoints showed normalization in ALP levels in only elafibranor-treated patients (15% for elafibranor 80 mg plus UDCA vs 0% for placebo plus UDCA).²

The present analysis examined cystatin C (CysC) and serum creatinine (SCr) through week 52 of ELATIVE. Additionally, investigators calculated estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD‑EPI) and Modification of Diet in Renal Disease (MDRD) equations.¹

Of note, patients with renal impairment, including chronic kidney disease, defined as eGFR <60 mL/min/1.73 m2, were not eligible to participate in the study.¹

Among the 161 patients who were randomly assigned to receive elafibranor (n = 108) or placebo (n = 53) in ELATIVE, investigators noted median levels of renal parameters were similar across both groups 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, while changes in SCr were 0.010 mg/dL and −0.009 mg/dL, respectively.¹

The median eGFR remained stable in both treatment groups through week 52, and the median change from baseline through week 52 in CysC-based eGFR was similar between the elafibranor (0.00 mL/min/1.73 m2) and placebo (−3.40 mL/min/1.73 m2) groups. Investigators did not find changes in CysC-based eGFR to be associated with corresponding changes in SCr and eGFR.¹

Acute kidney injury was reported in 3 (2.8%) patients receiving elafibranor and in 1 (1.9%) receiving placebo. Investigators pointed out 2 out of 3 patients with acute kidney injury receiving elafibranor had type 2 diabetes.¹

“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 said.

Editors’ note: Kugelmas has relevant disclosures with 89bio, Abbvie, Altimmune, AstraZeneca, Boehringer Ingelheim, CymaBay, Genfit, Gilead, Intercept, Ipsen, Madrigal, Novo Nordisk, and others.

References

1. ^{Kugelmas M, Levy C, Antunes N, et al. Elafibranor has no impact on markers of renal function in primary biliary cholangitis: results from the phase III ELATIVE® trial. 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 22, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc}