Inventiva announced the publication in Nature Communications of additional results from NATIVE Phase IIb clinical trial demonstrating improvement of markers of cardiometabolic health in patients with MASH/NASH treated with lanifibranor. In the NATIVE Phase IIb clinical trial which demonstrated improvement on liver histology following a 24-week period with lanifibranor 800mg and 1200mg daily, including NASH resolution and fibrosis improvement, a broad panel of markers of cardiometabolic health were also measured. Following lanifibranor treatment, the trial demonstrated significant improvement in patients with MASH/NASH with and without Type 2 Diabetes and with or without obesity of markers of insulin resistance (fasting insulin level, HOMA-IR), glycemic control (fasting glucose, HbA1c), lipid metabolism (triglycerides, HDL-C, APO-B, APO-B/APO-A1), adiponectin, systemic inflammation (hs-CRP, ferritin), diastolic blood pressure and hepatic steatosis (histological grading and ultrasound-based (Fibroscan CAPTM)).

Importantly, lanifibranor treatment also led to lower fasting glucose to normal levels in 71% of patients with MASH/NASH and prediabetes treated with the 1200mg dose and 67% of patients treated with the 800mg dose versus 11% of patients on placebo. In addition, no patients treated with either dose of lanifibranor with MASH/NASH and normoglycemia at baseline progressed to prediabetes at week 24, versus 26% of patients in the placebo arm. Furthermore, 38% and 44% of patients with MASH/NASH and high cardiovascular risk (based on markers of lipids and inflammation) treated with 1200mg and 800mg of lanifibranor, respectively, improved to intermediate or low cardiovascular risk at week 24, and 44% and 35% of patients at intermediate risk improved to low risk when treated with 1200mg and 800mg of lanifibranor, respectively.

However, in the placebo arm, only 26% of patients at high cardiovascular risk improved to intermediate risk and 13% improved from intermediate to low cardiovascular risk. The weight gain observed in a portion of the patient population treated with lanifibranor was shown to be associated with improvement of all markers of cardiometabolic health, similarly to patients treated with lanifibranor who maintained a stable weight throughout the study. This finding is in contrast to the weight gain observed in patients on placebo, which was associated with a worsening of cardiometabolic markers.

These results highlight the critical difference between the weight gain that can be observed with lanifibranor which can be defined as metabolically healthy and is associated with an improvement in insulin resistance, and the weight gain observed in patients under placebo which is metabolically unhealthy and is influenced by lifestyle. In addition, the increase in adiponectin levels following treatment with 1200mg and 800mg of lanifibranor occurred in 95% and 86% of patients, respectively, versus only in 10% of patients in the placebo arm. The increase in adiponectin level at week 24 was correlated with improvement of markers of insulin resistance, glycemic control, lipid metabolism and steatosis, as well as hs-CRP, aminotransferases and improvement in liver histological endpoints for disease activity and fibrosis.