Kris Kowdley, MD: Elafibranor Remains Safe, Efficacious for PBC Through 3 Years

Open-label extension data from the ongoing phase 3 ELATIVE study is providing clinicians with an overview of the long-term benefit of second-line treatment with elafibranor (Iqirvo) for primary biliary cholangitis (PBC).¹

The findings were presented in a late-breaking abstract 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 the Liver Institute Northwest, and demonstrate sustained improvements in biomarkers of cholestasis and pruritus, stabilization of surrogates for fibrosis, and improvements in pruritus up to 3 years.¹

“The way we treat PBC is evolving,” Kowdley explained in an interview with HCPLive, describing how the addition of obeticholic acid (Ocaliva) as the first second-line therapy in 2016 sparked a major shift in treatment that further changed with the addition of elafibranor. “We used to put patients on ursodeoxycholic acid and hope for the best… [now] our goal is to try to reduce alkaline phosphatase levels as much as possible and to normalize them.”

On June 10, 2024, elafibranor became the first US Food and Drug Administration-approved peroxisome proliferator-activated receptor (PPAR) agonist indicated for the second-line treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. The decision was based on 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 80 mg once daily versus placebo.²

Now, interim data from the ELATIVE open-label extension add to this understanding of elafibranor for the treatment of PBC, suggesting it leads to sustained improvements in biomarkers of cholestasis and pruritus and stabilization of surrogates for fibrosis up to week 156 while remaining well-tolerated.

“This open-label extension study shows that we can maintain the response, more patients will achieve that response, more patients can achieve alkaline phosphatase normalization, and we're seeing improvement in pruritus, which is very reassuring for both telling the patients that they're reducing their risk of adverse long term outcomes but also helping to modify or mitigate their symptoms,” Kowdley said.

Editors’ note: Kowdley has relevant disclosures with CymaBay, Genfit, Gilead, Intercept, Ipsen, Madrigal, Mirum, Pfizer, NovoNordisk, 89Bio, AbbVie, and others.

References

1. ^{Kowdley K, Bowlus CL, Levy C, et al. 5041 - Long-term efficacy and safety of elafibranor in primary biliary cholangitis: Interim results from the open-label extension of the ELATIVE® trial up to 3 years. 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 18, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc}