IPSEY - GENFIT: Results from Ipsen's ELATIVE® pivotal Phase III trial of elafibranor in PBC presented as late breaking data at AASLD congress and published in New England Journal of Medicine | Benzinga
- ELATIVE® Phase III trial confirms potential for investigational elafibranor as a novel, first-in-class, dual PPAR ?,? agonist for patients with Primary Biliary Cholangitis.
- Elafibranor demonstrates significant improvements in biomarkers of disease progression versus placebo, including significant treatment benefit with improvement in biochemical response and alkaline phosphatase (ALP) normalization, along with patient-reported outcomes data suggesting a possible improvement in pruritus.
- Elafibranor was generally well-tolerated with a well-documented safety profile consistent with previous trials.
Paris (France), November 13, 2023 – Ipsen ((Euronext: IPN, OTC:IPSEY) and GENFIT (Nasdaq and Euronext: GNFT) today announced full results from the pivotal Phase III ELATIVE® trial, which are being presented in a late-breaking oral session (Abstract #484, Monday, 13 November at 16.45 EST) at the American Association for the Study of Liver Diseases (AASLD) and simultaneously published in New England Journal of Medicine (NEJM). This trial evaluated the efficacy and safety of investigational elafibranor, an oral, dual PPAR ?,? agonist, as a potential novel class of treatment for patients with the rare, autoimmune cholestatic liver disease, Primary Biliary Cholangitis (PBC).
Results show statistically significant improvements in biomarkers of disease progression across key endpoints with a significant treatment benefit achieved in the primary composite endpoint, demonstrating a 47% placebo-adjusted difference (P<0.001) between patients on elafibranor 80mg (51%) compared with patients on placebo (4%) achieving a biochemical response. In the trial, a biochemical response is defined as alkaline phosphatase (ALP) <1.67 x upper limit of normal (ULN), an ALP decrease ? 15 percent and total bilirubin (TB) ? ULN at 52 weeks. ALP and bilirubin are important predictors of PBC disease progression. Reductions in levels of both can indicate reduced cholestatic injury and improved liver function.
Only patients receiving elafibranor achieved normalization of ALP (upper limit of normal 104 U/L in females and 129 U/L in males) at Week 52 (15% vs 0% placebo, P=0.002), a key secondary endpoint of the trial. The significant biochemical effect of elafibranor measured by ALP reduction was further supported by data demonstrating reductions from baseline in ALP levels were rapid, seen as early as Week 4 in the elafibranor group, and were sustained through Week 52, with a decrease in ALP of 41% on elafibranor compared with placebo.
"When managing PBC, our first goal is to effectively control the disease progression which can lead to liver failure. The results from ELATIVE® provide compelling evidence that elafibranor has the potential to achieve this goal, with evidence of a highly significant treatment benefit that is associated with improved clinical outcomes," said Dr Christopher Bowlus, Professor of Gastroenterology and Hepatology, University of California Davis, U.S. "In addition, our patients need relief from the significant symptom burden of PBC, particularly those with moderate to severe itch. Data from ELATIVE® demonstrated the possibility of improved pruritus for patients taking elafibranor compared with those on placebo. Taken together, these data suggest elafibranor could offer an effective new treatment opportunity for PBC management."
ELATIVE® investigated the effect of treatment with elafibranor on pruritus (severe itch) across three separate patient-reported outcome measures. On the key secondary endpoint using the PBC Worst Itch NRS score, the reduction of pruritus observed for elafibranor versus placebo was not statistically significant (LS mean, –1.93 versus –1.15; difference, –0.78; 95% CI, –1.99 to 0.42; P=0.20). Two other secondary patient-reported outcome measures were used to assess itch, and greater reductions in pruritus were observed with elafibranor compared with placebo at Week 52, according to the itch domain of PBC-40 quality of life questionnaire (LS mean difference -2.3; 95% CI, -4.0 to -0.7) and 5-D Itch total score (LS mean difference, -3.0; 95% CI, -5.5 to -0.5).
"We believe these data suggest that elafibranor could be a paradigm-changing treatment meeting the unmet need for an effective second-line option," said Christelle Huguet, EVP and Head of Research and Development, Ipsen. "These data from ELATIVE® have provided a better understanding of how we can effectively manage both disease progression and the symptom burden still experienced by many people living with PBC. It would not have been possible for us to investigate the potential for new innovative treatments without the involvement of the patients and their wider families and caregivers, to whom we are immensely grateful. We are also enormously grateful to the study investigators, who have supported us and provided us with the benefit of their expertise in designing and running this study."
PBC is a rare, autoimmune, cholestatic liver disease, affecting approximately nine women for every one man. A build-up of bile and toxins (cholestasis) and chronic inflammation causes irreversible fibrosis (scarring) of the liver and destruction of the bile ducts. It is a life-long condition that can worsen over time if not effectively treated, leading to liver transplant and in some cases, premature death. PBC impacts patients' daily lives through debilitating symptoms including, most commonly, pruritus and fatigue. Currently, there are no approved treatments available that can effectively manage both disease progression and life-impacting symptoms.
"Living with PBC can be very challenging for many people. The fear of the disease progressing hangs over you, and you have to manage as best you can ...