Inventiva publishes new NATIVE Phase IIb trial results showing cardiometabolic health improvements with lanifibranor

In a recent publication in Nature Communications, Inventiva, a clinical-stage biopharmaceutical company, has shared additional findings from its NATIVE Phase IIb clinical trial. This trial focuses on the treatment of patients with metabolic dysfunction-associated steatohepatitis (MASH), also known as non-alcoholic steatohepatitis (NASH), using the drug lanifibranor. The results reveal significant improvements in cardiometabolic health markers among the patients treated.

The NATIVE Phase IIb trial was a rigorous 24-week study that evaluated the effects of lanifibranor on liver histology and a broad array of cardiometabolic health indicators. Two doses of lanifibranor (800mg and 1200mg) were administered daily to patients, and the outcomes were compared with those of a placebo group. The trial included patients with and without Type 2 Diabetes and those with or without obesity.

Key improvements were noted in several areas, including insulin resistance, lipid metabolism, glycemic control, systemic inflammation, hepatic steatosis, and diastolic blood pressure. Lanifibranor treatment notably reduced fasting insulin levels and HOMA-IR, indicating better insulin sensitivity. Glycemic control was also enhanced, with reductions in fasting glucose and HbA1c levels. Lipid profiles improved, as shown by decreases in triglycerides, APO-B levels, and the APO-B/APO-A1 ratio, while HDL-cholesterol levels increased. Systemic inflammation markers such as hs-CRP and ferritin were reduced, demonstrating reduced inflammatory activity. Additionally, hepatic steatosis showed improvement based on histological grading and ultrasound-based evaluations.

Among patients with prediabetes at the start of the trial, a significant majority achieved normal fasting glucose levels by the end of the treatment with lanifibranor. In contrast, none of the patients who began with normal glucose levels transitioned to prediabetes during treatment, unlike those in the placebo group. Adiponectin levels, which are associated with improved cardiometabolic health, were significantly increased in patients treated with lanifibranor, while they remained unchanged in the placebo group.

Furthermore, patients with high cardiovascular risk treated with lanifibranor demonstrated a notable shift to intermediate or low cardiovascular risk compared to the placebo group. This improvement was consistent across different doses of the drug. The weight gain observed in some patients treated with lanifibranor was associated with positive cardiometabolic outcomes, contrasting with the metabolically unhealthy weight gain seen in the placebo group.

Lanifibranor, Inventiva’s lead product candidate, acts as a pan-PPAR agonist, targeting all three PPAR isoforms to induce anti-fibrotic, anti-inflammatory, and beneficial metabolic changes. This makes it unique among PPAR agonists currently in clinical development for MASH/NASH. The favorable tolerability profile observed in clinical trials supports its potential as a therapeutic option.

The NATIVE Phase IIb trial enrolled 247 patients across multiple sites globally. The primary aim was to assess lanifibranor’s efficacy in reducing liver inflammation and ballooning, with secondary endpoints including improvements in steatosis, inflammation, fibrosis, and various metabolic markers.

These findings underscore the potential of lanifibranor to address the complex disease biology of MASH/NASH, from insulin resistance to fibrosis. The improvements in cardiometabolic health markers irrespective of patients’ diabetes and obesity status highlight its broad therapeutic potential. Inventiva’s ongoing Phase III clinical trial, NATiV3, aims to further validate these promising results and explore lanifibranor’s potential as a comprehensive treatment for MASH/NASH.