ELATIVE: Elafibranor Slows Disease Progression, Improves Itch-Related QoL in PBC

Ipsen has announced new data from the phase 3 ELATIVE trial demonstrating the efficacy of elafibranor in managing primary biliary cholangitis (PBC) progression after 78 weeks of treatment.¹

The data were presented during a late-breaking session at the European Association for the Study of the Liver (EASL) Congress in Milan, Italy, and showed 70% of patients treated with elafibranor achieved the composite endpoint of biochemical response after 78 weeks. Additional data from the itch domain of the PBC-40 and 5-D Itch questionnaires also highlighted elafibranor’s potential to improve itch-related quality of life in patients with moderate-to-severe pruritus.¹

“When you have a patient with PBC, it’s vital to manage disease progression, to prevent or delay liver damage or failure. You also want to provide relief from distressing symptoms because they can have a very detrimental impact on quality of life,” Christopher Bowlus, MD, professor of gastroenterology and hepatology at the University of California Davis, said in a press release.¹ “These new data from ELATIVE provide further evidence that elafibranor has the potential to address the two priority treatment goals by demonstrating longer-term improvements in the prognostic markers of disease progression, as well as potential improvements in pruritus-symptom severity and impacts on the quality of life.”

A novel, potential first-in-class, dual peroxisome activated receptor (PPAR) alpha/delta (α,δ) agonist, elafibranor was granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) in adults with PBC who have an inadequate response to ursodeoxycholic acid (UDCA) in 2019.² It has not yet received approval from any regulatory authorities, although it is currently under review by the FDA, the European Medicines Agency, and the UK Medicines and Healthcare Products Regulatory Authority. Of note, the data presented at EASL comes less than a week ahead of elafibranor’s anticipated Prescription Drug User Fee Act (PDUFA) date on June 10, 2024.^1,3

ELATIVE is a multi-center, randomized, double-blind, placebo-controlled phase 3 clinical trial evaluating the efficacy and safety of elafibranor 80 mg once daily versus placebo for the treatment of patients with PBC with an inadequate response or intolerance to UDCA, the existing first-line therapy for PBC. The trial enrolled 161 patients who were randomly assigned in a 2:1 ratio to receive elafibranor 80 mg once daily or placebo. Those with an inadequate response to UDCA continued to receive UDCA in combination with elafibranor or placebo, while patients unable to tolerate UDCA received only elafibranor or placebo.¹

Patients continued their assigned treatment after week 52 until all had completed their treatment or for a maximum of 104 weeks. Data was also collected during this period, and additional analyses were conducted with a focus on week 78.¹

Data presented at EASL for patients who had their week-78 double-blind visit (n = 30 elafibranor; n = 13 placebo) showed the efficacy of elafibranor was sustained after 78 weeks of treatment, with 70% of patients on elafibranor meeting the composite endpoint of biochemical response, defined as alkaline phosphatase (ALP) <1.67 x upper limit of normal (ULN), an ALP decrease ≥ 15%, and total bilirubin (TB) ≤ ULN, versus 0% on placebo. Of note, ALP normalization for patients on elafibranor was sustained through week 78 as well as across other important biomarkers of liver injury, including total bilirubin and gamma-glutamyl transferase.¹

New patient-reported outcome data from ELATIVE at week 52 were also presented and demonstrated the potential beneficial effect of elafibranor on itch-related quality of life, including sleep and functioning. Results showed treatment with elafibranor led to greater reductions in 5-D itch score and a clinically meaningful reduction in the itch domain of PBC-40 versus placebo. In the 5-D itch duration domain, reduced itching was reported by 58% of patients receiving elafibranor at week 52 compared with 27% on placebo. Additionally, 80% of patients receiving elafibranor improved to no sleep disturbance or only occasional delay compared with 30% on placebo.¹

“There are a significant proportion of people living with PBC who experience worsening disease and debilitating symptoms despite being on treatment. These long-term data from the Phase III ELATIVE study further demonstrate the potential for elafibranor to provide an effective treatment option for these patients,” Sandra Silvestri, MD, Executive Vice President and Chief Medical Officer of Ipsen, said in a press release.¹ “A lack of effective management can lead to advanced forms of the disease where liver transplantation may be the only option. Transplants are not trivial, so we must and can do better to preserve native liver function for people living with PBC.”

References:

1. ^{Ipsen. Ipsen presents long-term elafibranor efficacy and itch-related quality of life data in patients with primary biliary cholangitis. Press releases. June 5, 2024. Accessed June 5, 2024. https://www.ipsen.com/press-releases/ipsen-presents-long-term-elafibranor-efficacy-and-itch-related-quality-of-life-data-in-patients-with-primary-biliary-cholangitis/}
2. ^{Genefit. GENFIT announces FDA Grant of Breakthrough Therapy Designation to Elafibranor for the Treatment of PBC. April 18, 2019. Accessed June 5, 2024. https://ir.genfit.com/news-releases/news-release-details/genfit-announces-fda-grant-breakthrough-therapy-designation}
3. ^{Ipsen. Ipsen confirms U.S. FDA grants priority review for New Drug Application for elafibranor for the treatment of rare cholestatic liver disease, PBC. Press Releases. December 7, 2023. Accessed June 5, 2024. https://www.ipsen.com/press-releases/ipsen-confirms-u-s-fda-grants-priority-review-for-new-drug-application-for-elafibranor-for-the-treatment-of-rare-cholestatic-liver-disease-pbc/}