Marlyn Mayo, MD: Elafibranor’s Safety, Efficacy in Patients with Advanced PBC

Findings from a new analysis of the phase 3 ELATIVE trial supporting elafibranor (Iqirvo)’s recent US Food and Drug Administration approval for primary biliary cholangitis (PBC) suggest the peroxisome proliferator-activated receptor (PPAR) agonist’s benefit for patients with advanced disease.

The data were presented in a late-breaking abstract at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania, by Marlyn Mayo, MD, a professor of internal medicine at UT Southwestern Medical Center, and showed elafibranor provided a consistent treatment effect regardless of disease stage and had a positive impact on disease stabilization.

“The data on elafibranor in general are pretty new,” Mayo explained to HCPLive. “This is a very recently approved drug in the US and the phase 3 data are actually not that old, and we're just now starting to delve deeper into the details of that phase 3 data.”

In ELATIVE, 13 times more patients achieved the composite primary endpoint of biochemical response when treated with elafibranor plus ursodeoxycholic acid (UDCA) (n = 108) versus placebo plus UDCA (n = 53) (51% vs 4% for a 47% treatment difference, respectively). Secondary endpoints showed normalization in alkaline phosphatase levels only in elafibranor-treated patients (15% for elafibranor plus UDCA vs 0% for placebo plus UDCA).

“This particular presentation that I gave today was looking specifically at that segment of patients who had more advanced disease, and that's really important because the advanced disease patients are the ones that are going to run into trouble,” Mayo said. “They're the ones that have the biggest need for additional therapy, and they're also a group that historically doesn't tolerate medications as well as people with early-stage disease."

Findings from the analysis presented at ACG showed among those with advanced-stage PBC (n = 54), biochemical response occurred in 45.7% of patients receiving elafibranor and 0% receiving placebo. The advanced versus early risk difference was –0.016 (95% confidence interval [CI], –0.216 to 0.184) and the elafibranor versus placebo risk difference was 0.457 (95% CI, 0.230 to 0.618) for advanced disease.

“I think what it added is that we can now say with pretty good conviction that this drug appears to be very well tolerated in patients with advanced disease,” Mayo said, also mentioning how these results give providers a new sense of confidence when prescribing elafibranor in patients with advanced fibrosis and early cirrhosis. Still, she pointed to the need for data in patients with decompensated cirrhosis, as no patients in ELATIVE had decompensated cirrhosis at baseline.

Editors’ note: Mayo has relevant disclosures with CymaBay, GENFIT, Gilead, GlaxoSmithKline, Ironwood, Intercept, Ipsen, and Mirum.

References

1. ^{Brooks, A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed October 29, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc}
2. ^{Mayo MJ, Kowdley KV, Bowlus CL, et al. 45 - Impact of Elafibranor on Markers of Disease Activity and Progression in Patients With Advanced Primary Biliary Cholangitis (Late-Breaking Abstract). Paper presented at: ACG 2024 Annual Scientific Meeting. Philadelphia, Pennsylvania. October 25-30, 2024.}