Positive LEGEND Trial Outcomes: Lanifibranor and Empagliflozin for MASH/NASH and T2D

In a recent clinical trial, the drug lanifibranor, developed by Inventiva, demonstrated significant progress in managing metabolic dysfunction-associated steatohepatitis (MASH), also referred to as non-alcoholic steatohepatitis (NASH), alongside Type 2 Diabetes (T2D). The Phase II Proof-of-Concept trial, known as LEGEND, involved a 24-week treatment period where patients received either lanifibranor alone, a combination of lanifibranor and empagliflozin, or a placebo. The trial aimed to evaluate the safety and efficacy of this treatment approach for non-cirrhotic MASH/NASH and T2D patients.

Key findings from the LEGEND trial include a substantial reduction in Hemoglobin A1c (HbA1c) levels for both the group receiving lanifibranor and those also treated with empagliflozin, compared to the placebo group, which showed an increase. The study also reported significant improvements in several markers of liver injury, glucose and lipid metabolism, and hepatic steatosis. Notably, patients treated with the combination maintained stable weight, addressing concerns of weight gain associated with lanifibranor treatment alone.

Furthermore, the ratio of visceral to subcutaneous abdominal fat decreased with the treatment, indicating a shift towards healthier adipose tissue. The 24-week treatment with lanifibranor was well-tolerated, with no safety issues reported. Inventiva plans to present more detailed results at upcoming scientific conferences and is considering publication.

Dr. Michael Cooreman, Chief Medical Officer at Inventiva, highlighted the potential of lanifibranor to address the complex disease biology of MASH and T2D. He emphasized the drug's unique mechanism of action, which could cater to the significant medical needs of patients with both conditions. The study's co-principal investigators, Dr. Onno Holleboom and Prof. Michelle Lai, also praised the trial's design and the positive impact of the treatment on steatosis, inflammation, fibrosis, and weight stabilization.

The LEGEND trial's success has led Inventiva to halt recruitment as per protocol, and the company anticipates sharing more insights through presentations and publications. The trial's results are promising for the future treatment of MASH/NASH and T2D, especially considering the substantial overlap between the two conditions and the lack of approved therapies for MASH/NASH to date.