Inventiva to Present Final Phase 2 Study Data on Lanifibranor and Empagliflozin Combo at AASLD Meeting

Inventiva, a clinical-stage biopharmaceutical company based in Daix, France and Long Island City, New York, has announced the presentation of the final analysis of their Phase 2 clinical trial LEGEND. The results were shared on Monday, November 18, 2024, at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® 2024, held in San Diego, California. The trial evaluated the effectiveness of lanifibranor alone and in combination with empagliflozin in patients suffering from Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Type 2 Diabetes (T2D).

The primary efficacy endpoint of the LEGEND trial was to assess the reduction in Hemoglobin A1c (HbA1c) levels, a key marker for blood sugar control. The trial results indicated that both the lanifibranor-only group and the combination therapy group experienced significant reductions in HbA1c levels compared to the placebo group. By week 24, 50% of patients treated with lanifibranor alone or in combination with empagliflozin had HbA1c levels below 6.5%. Furthermore, 58% of patients on lanifibranor alone and 80% on the combination therapy had at least a 1% decrease in HbA1c levels, in stark contrast to the placebo group, which saw no reduction.

Additionally, the trial demonstrated improvements in liver health and cardiometabolic markers in patients who received the treatments. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) showed a reduction in hepatic steatosis by 49% in the lanifibranor group and 41% in the combination group. Other notable improvements included decreases in the composite MASH activity and fibrosis scores measured with cT1.

Moreover, adiponectin levels, which are indicative of enhanced insulin sensitivity and anti-inflammatory effects, increased significantly in the treatment groups. The lanifibranor group saw a three-fold increase, and the combination group observed a similar rise, while no such increase was recorded in the placebo group.

The study also examined the impact on body weight. A slight weight gain of 3.6% was noted in the lanifibranor-only group, whereas the combination therapy group maintained stable weight. Importantly, there was a reduction in the ratio of visceral abdominal fat to subcutaneous fat in both treatment groups, which suggests a shift towards a healthier fat distribution. The lanifibranor group saw a 5% decrease, and the combination group experienced an 18% reduction, compared to a 2% increase in the placebo group.

Liver function tests, including ALT, AST, and GGT, along with markers of liver fibrosis (TIMP-1, P3NP, Pro-C3), showed notable improvement in the patients treated with lanifibranor, either alone or with empagliflozin. Other cardiometabolic health markers, such as insulin sensitivity (HOMA-IR), inflammation (hs-CRP), ferritin levels, glycemia, and lipid profile (HDL-C, triglycerides), also displayed positive trends in both treatment groups.

Dr. Michael Cooreman, Chief Medical Officer of Inventiva, expressed satisfaction with the trial outcomes, emphasizing the potential benefits of lanifibranor both as a monotherapy and in combination with empagliflozin for patients with MASH and T2D. Dr. Nezam Afdhal, Chief of Gastroenterology at Beth Israel Deaconess Medical Center and Professor of Medicine at Harvard Medical School, highlighted the significance of these results in addressing insulin resistance, a core issue in MASH.

The LEGEND trial involved patients with MASH and T2D, having HbA1c levels between 7-10% at the start. It was designed as a double-blind trial for lanifibranor and placebo, while the combination therapy with empagliflozin was open-label. The promising results from this trial underscore the potential of lanifibranor, both alone and in combination with empagliflozin, to offer effective treatment options for patients with MASH and T2D, addressing significant unmet medical needs in these conditions.