Ipsen will present promising new data from its Phase II ELMWOOD clinical study evaluating elafibranor for primary sclerosing cholangitis (PSC) at the upcoming European Association for the Study of the Liver (EASL) Congress on May 10, 2025. The late-breaking abstract highlights the potential of elafibranor as the first treatment for this rare liver disease that currently has no approved therapies.
The 12-week randomized, double-blind, placebo-controlled study involved 68 patients with PSC who received either elafibranor 80 mg, elafibranor 120 mg, or placebo. Results demonstrated a favorable safety profile and significant dose-dependent efficacy for the investigational treatment.
Safety and Tolerability Profile
Treatment-emergent adverse events were experienced by 68.2% of patients on elafibranor 80 mg, 78.3% on 120 mg, and 69.6% on placebo. Notably, adverse events leading to treatment discontinuation were less common with elafibranor (4.5% for 80 mg and 4.3% for 120 mg) compared to placebo (8.7%). No serious adverse events occurred in patients receiving elafibranor, while 4.3% of placebo patients experienced serious adverse events.
"These results are a testament to our ongoing commitment to advancing potential treatments for rare liver diseases where there is a significant unmet need and few options for patients currently exist," said Christelle Huguet, PhD, Executive Vice President and Head of Research and Development at Ipsen. "These results are encouraging and reinforce elafibranor's action as a PPARα/δ agonist in potentially treating multiple liver diseases, like PSC."
Significant Improvements in Liver Parameters
The efficacy data revealed significant dose-dependent reductions in alkaline phosphatase (ALP), a key biomarker of disease activity in PSC. Patients receiving elafibranor 80 mg and 120 mg showed significant reductions in ALP at week 12 compared to placebo (-103.2 U/L and -171.1 U/L vs +32.1 U/L; p < 0.0001), with improvements observed as early as week 4.
Similar positive trends were observed in other liver biochemical parameters, including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), which are important markers of disease progression.
Stabilization of Fibrosis and Improvement in Symptoms
Patients treated with elafibranor showed stabilization in Enhanced Liver Fibrosis (ELF), a non-invasive marker of liver fibrosis, compared to those on placebo at week 12. This suggests potential for the drug to slow disease progression.
Additionally, patients receiving the higher 120 mg dose of elafibranor experienced significant improvements in pruritus (itching) compared to placebo, as measured by the Worst Itch Numeric Rating Scale (WI NRS) score (-0.96 vs -0.28; p<0.05). Pruritus is a common and distressing symptom for many PSC patients.
"These data from the ELMWOOD trial are encouraging, demonstrating positive safety and efficacy data for elafibranor as a potential treatment for PSC, where none currently exist," said Cynthia Levy, MD, Professor of Clinical Medicine and Hepatology at the University of Miami Miller School of Medicine. "PSC is a serious liver disease and currently, liver transplantation is the only treatment that can significantly improve the prognosis. These findings support further investigation in larger longer-term trials to fully evaluate the potential of elafibranor in PSC."
About Primary Sclerosing Cholangitis
PSC is a rare, chronic liver disease characterized by inflammation and scarring of the bile ducts, which can lead to liver damage and eventually liver failure. The exact cause remains unknown, but it is often associated with other autoimmune conditions, particularly inflammatory bowel disease.
Symptoms include itching, fatigue, jaundice, and abdominal pain. Over time, PSC can result in complications such as bile duct infections, liver cirrhosis, and an increased risk of liver cancer. Currently, there are no FDA or EMA approved therapies for PSC, making liver transplantation the only treatment that can significantly improve prognosis.
Elafibranor's Mechanism and Regulatory Status
Elafibranor is an oral peroxisome proliferator-activated receptor (PPAR) agonist that affects PPARα and PPARδ. Activation of these receptors decreases bile toxicity and improves cholestasis by modulating bile acid synthesis, detoxification, and transporters. It also has anti-inflammatory effects through multiple pathways.
The drug has already received regulatory approval under the brand name IQIRVO for the treatment of Primary Biliary Cholangitis (PBC). It received U.S. FDA accelerated approval in June 2024, EU conditional approval in September 2024, and UK MHRA approval in October 2024 for PBC treatment in combination with ursodeoxycholic acid (UDCA) in adults with inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.
Ongoing Research
The open-label 96-week extension of the ELMWOOD study evaluating the safety and efficacy of elafibranor 120 mg remains ongoing. This longer-term data will be crucial to fully assess the drug's potential in PSC treatment.
Elafibranor was originally developed by GENFIT, with Ipsen licensing the exclusive worldwide rights (except China, Hong Kong, Taiwan, and Macau) in 2021. The drug's potential to treat multiple liver diseases highlights Ipsen's commitment to addressing significant unmet needs in rare liver conditions.
