Phase 3 Trial of Elafibranor in Liver Disease Meets Primary Endpoint: Potential First-in-Class Oral Therapy on Track for Global Regulatory Submissions

▎WuXi

Edited by Kant Content Team

Recently, Ipsen and GENFIT jointly announced the full results of their pivotal Phase 3 ELATIVE trial, which was simultaneously presented at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting and published in The New England Journal of Medicine. The trial evaluated the efficacy and safety of their investigational small molecule elafibranor for the treatment of patients with primary biliary cholangitis (PBC).The positive results of this trial will support the global regulatory submission for elafibranor as a potential therapy for PBC.

Analysis shows that patients experienced statistically significant improvements in biomarkers of disease progression at all key endpoints.The primary composite endpoint achieved significant therapeutic benefit, showing a 47% difference in the proportion of patients achieving biochemical response between the 80 mg elafibranor group (51%) and the placebo group (4%) (P<0.001).In the trial, biochemical response was defined as alkaline phosphatase (ALP) <1.67× upper limit of normal (ULN) at week 52, with a reduction in ALP ≥15% and total bilirubin (TB) ≤ULN. ALP and bilirubin are important predictors of PBC disease progression. Reductions in both levels may indicate alleviation of cholestatic injury and improvement in liver function.

In addition,Only patients treated with elafibranor reached normal ALP levels at week 52, including 15% of the drug group and 0% of the placebo group (P=0.002), a key secondary endpoint of the trial.Elafibranor also showed a significant biochemical effect with a rapid reduction in ALP levels from baseline. A decrease in ALP levels was observed in patients taking elafibranor as early as week 4 and continued through week 52, with a 41% greater reduction compared to the placebo group.

Image Source: 123RF

Elafibranor was well tolerated, with a safety profile consistent with previous trials.

Elafibranor is a once-daily, oral, potential "first-in-class" dual peroxisome proliferator-activated receptor (PPAR) α/δ agonist, currently under investigation for the treatment ofRare AutoimmunePBC patients.Simultaneously targeting the activation of PPAR α/δ can potentially treat inflammation, cholestasis, and fibrosis in PBC. In 2019, the U.S. FDA granted elafibranor Breakthrough Therapy designation for the treatment of adult PBC patients with an inadequate response to ursodeoxycholic acid (UDCA).

[1] Results from Ipsen’s ELATIVE® pivotal Phase III trial of elafibranorin PBC presented as late breaking data at AASLD congress and published in NewEngland Journal of Medicine. Retrieved November 14, 2023 from https://www.ipsen.com/press-releases/assld_elative/

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