공시 • Nov 14
Ipsen and GENFIT Announces Full Results from the Pivotal Phase III ELATIVE Trial
Ipsen and GENFIT 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 Disease (AASLD) and simultaneously published in the New England Journal of Medicine (NEJM). This trial evaluated the efficacy and safety of investigational elafibranor, an oral, dual PPAR a,d 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% 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. 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). 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 patient’s 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. Elafibranor was well tolerated in the trial. Similar percentages of patients in the treatment group and the placebo group experienced adverse events, treatment-related adverse events, severe or serious adverse events or adverse events leading to discontinuation. Adverse events occurring in >10% of patients and more frequently on elafibranor versus placebo included abdominal pain, diarrhea, nausea, and vomiting. Elafibranor has a well-documented safety profile across a broad patient population and is consistent with cumulative safety data from past elafibranor trials in other indications, including NASH.