- ELATIVE® Phase III trial confirms potential for investigational elafibranor as a novel, first-in-class, dual PPAR α,δ 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.
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
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
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 with the daily symptom burden, symptoms that can sometimes be so debilitating it takes every ounce of strength to get through another day,” explained
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.
Data from ELATIVE® are being used to support submissions for elafibranor as a treatment for PBC with regulatory authorities worldwide.
ENDS
ABOUT ELATIVE®
ELATIVE® is a multi-center, randomized, double-blind, placebo-controlled Phase III clinical trial, with an open-label long-term extension (NCT03124108). ELATIVE® is evaluating the efficacy and safety of elafibranor 80mg once daily versus placebo for the treatment of patients with PBC with an inadequate response or intolerance to ursodeoxycholic acid (UDCA), the existing first-line therapy for PBC. The trial enrolled 161 patients who were randomized 2:1 to receive elafibranor 80mg once daily or placebo. Patients with an inadequate response to UDCA would continue to receive UDCA in combination with elafibranor or placebo, while patients unable to tolerate UDCA would receive only elafibranor or placebo.
ABOUT ELAFIBRANOR
Elafibranor is a novel, oral, once-daily, dual peroxisome activated receptor (PPAR) alpha/delta (α,δ) agonist, currently under investigation as a treatment for patients with PBC, a rare liver disease. Concurrent α,δ activation targets inflammation, cholestasis and fibrosis in PBC. In 2019, elafibranor was granted a Breakthrough Therapy Designation by the FDA in adults with PBC who have an inadequate response to UDCA. Elafibranor has not received approval by regulatory authorities anywhere in the world.
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ABOUT IPSEN
Ipsen is a global, mid-sized biopharmaceutical company focused on transformative medicines in Oncology, Rare Disease and Neuroscience. With total sales of €3.0bn in FY 2022, Ipsen sells medicines in over 100 countries. Alongside its external-innovation strategy, the Company’s research and development efforts are focused on its innovative and differentiated technological platforms located in the heart of leading biotechnological and life-science hubs: Paris-Saclay, France;
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Attachment
GENFIT : Results from Ipsen’s ELATIVE® pivotal Phase III trial of elafibranor in PBC presented as late breaking data at AASLD congress and published inNew England Journal of Medicine
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