• Trial met primary endpoint with a statistically significant higher percentage of patients achieving a clinically meaningful cholestasis response compared to placebo
  • Elafibranor was well tolerated with a safety profile consistent with previous studies
  • Results position elafibranor as a potentially important new treatment option, where there is still high unmet need
  • Ipsen intends to submit regulatory applications for elafibranor following discussions with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA)

PARIS, France I June 30, 2023 I Ipsen (Euronext: IPN; ADR: IPSEY) and GENFIT (Nasdaq and Euronext: GNFT) today announced positive topline data from the pivotal ELATIVE® Phase III trial. In the trial the efficacy and safety of elafibranor, an investigational dual α,δ PPAR agonist, is being assessed for the treatment of patients with the rare cholestatic liver disease, primary biliary cholangitis (PBC), who have an inadequate response or intolerance to the current standard of care therapy, ursodeoxycholic acid (UDCA).

The trial met its primary composite endpoint, with 51% of patients on elafibranor 80mg achieving a cholestasis response compared with 4% on placebo (p<0.0001). Cholestasis response is defined in the trial 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 disease progression. Reductions in levels of both can indicate reduced cholestatic injury and improved liver function.

The first secondary endpoint, normalization of ALP at Week 52, was also met with statistically significant improvements for investigational elafibranor compared with placebo. For the other secondary endpoint, a trend for pruritus improvement was observed with a greater decrease from baseline in the PBC Worst Itch NRS score for patients on elafibranor compared to placebo, which did not reach statistical significance. In the study, elafibranor was generally well tolerated with a safety profile consistent with that observed in previously reported studies.

These are encouraging results that suggest elafibranor could be an effective treatment to prevent progression of PBC in patients who have received UDCA. It has a good safety profile and was well- tolerated, and could provide an important new therapeutic option for long-term treatment of patients with this debilitating condition,” said Howard Mayer, Executive Vice President and Head of Research and Development for Ipsen. “PBC is a serious condition which, if not treated properly, can lead to progression of liver disease and ultimately liver failure. We are excited about the potential of this investigational treatment and Ipsen now intends to discuss these results with regulatory agencies and plans to move forward with regulatory submissions to the U.S. Food and Drug Administration and the European Medicines Agency.”

We are pleased by these results because PBC remains a disease where significant unmet medical needs exist”, added Pascal Prigent, Chief Executive Officer of GENFIT. “This long-awaited trial outcome is therefore good news for patients and for healthcare professionals who need more options to improve the clinical management of patients with PBC. It is also a gratifying recognition of the quality of our team’s work and of GENFIT’s ability to innovate and deliver tangible results.

PBC is a rare, progressive, autoimmune cholestatic liver disease1 in which bile ducts in the liver are gradually destroyed. The damage to bile ducts can inhibit the liver’s ability to rid the body of toxins, and can lead to scarring of liver tissue, known as cirrhosis.1 Common symptoms of PBC include fatigue and pruritus (itch), which can be severely debilitating.1 Untreated, PBC can lead to liver failure, or in some cases death. It is also a leading cause of liver transplantation. It primarily affects middle-aged women, with nine women diagnosed for every man. It is a disease where a significant proportion of patients are unable to benefit from existing therapies. The prevalence of people living with PBC is estimated to be between 23.9-39.2 per 100,000 in the U. S2 3and 22.27 per 100,000 in Europe.4

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 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.

Full data from the ELATIVE® trial will be presented at a future scientific congress.

GENFIT will host a conference call on June 30, 2023 at 8:00am ET / 1:00pm GMT / 2:00pm CET in English and in French

Both the English and French conference calls will be accessible on the investor page of our website, under the events section at https://ir.genfit.com/ or by calling 888-394-8218 (toll-free U.S. and Canada), 0800 279 0425 (toll-free UK) or 0805 101 219 (France) five minutes prior to the start time (confirmation code: 6752821). A replay will be available shortly after the call.

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. In 2019, it was granted a Breakthrough Therapy designation by the FDA in adults with PBC who have an inadequate response to ursodeoxycholic acid (UDCA). Elafibranor has not received approval by regulatory authorities anywhere in the world.

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; Oxford, U.K.; Cambridge, U.S.; Shanghai, China. Ipsen has around 5,400 colleagues worldwide and is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com

ABOUT GENFIT

GENFIT is a late-stage biopharmaceutical company dedicated to improving the lives of patients with rare and severe liver diseases characterized by high unmet medical needs. GENFIT is a pioneer in liver disease research and development with a rich history and strong scientific heritage spanning more than two decades. Thanks to its expertise in bringing early-stage assets with high potential to late development and pre-commercialization stages, today GENFIT boasts a growing and diversified pipeline of innovative therapeutic and diagnostic solutions. Its R&D pipeline covers six therapeutic areas via seven programs which explore the potential of differentiated mechanisms of action, across a variety of development stages (pre-clinical, Phase 1, Phase 2, Phase 3). These diseases are acute on-chronic liver failure (ACLF), hepatic encephalopathy (HE), cholangiocarcinoma (CCA), urea cycle disorders (UCD), organic acidemias (OA) and primary biliary cholangitis (PBC). Beyond therapeutics, GENFIT’s pipeline also includes a diagnostic franchise focused on NASH and ACLF. GENFIT has facilities in Lille and Paris (France), Zurich (Switzerland) and Cambridge, MA (USA). GENFIT is a publicly traded company listed on the Nasdaq Global Select Market and on compartment B of Euronext’s regulated market in Paris (Nasdaq and Euronext: GNFT). In 2021, IPSEN became one of GENFIT’s largest shareholders and holds 8% of the company’s share capital. For more information, visit www.genfit.com

1 Kimagi T, et al.. Orphanet J Rare Dis. 2008; 3:1
2 Lu et al. Clinical Gastro and Hepatol 2018; 16:1342-1350
3 Galoosian et al. Journal of Clinical and Transplantation Hepatology 2020; 8:49-60
4 Gazda J, et al. Can J GastroenterolHepatol. 2021 ; 915 -1525

SOURCE: Genfit