Inventiva, a clinical-stage biopharmaceutical company, announced a positive recommendation from the Data Monitoring Committee (DMC) for its NATiV3 Phase 3 clinical trial evaluating lanifibranor in patients with metabolic dysfunction-associated steatohepatitis (MASH), also known as non-alcoholic steatohepatitis (NASH). The DMC recommended continuing the trial without any modifications to the current protocol.
The recommendation stems from an unblinded review of safety data from over 1000 patients randomized in the main and exploratory cohorts of the NATiV3 trial. This includes data from over 800 patients treated for more than 24 weeks and 177 patients treated for more than 72 weeks. The DMC's assessment, while unblinded to them, remains blinded to Inventiva, ensuring objectivity in the trial's conduct.
The positive recommendation from the DMC reinforces the favorable safety and tolerability profile of lanifibranor, Inventiva's lead product candidate. This is particularly significant as the NATiV3 trial progresses towards its primary endpoint assessment.
Lanifibranor: A Pan-PPAR Agonist for MASH
Lanifibranor is an orally-available small molecule designed to induce anti-fibrotic, anti-inflammatory, and beneficial vascular and metabolic changes. It achieves this by activating all three peroxisome proliferator-activated receptor (PPAR) isoforms. PPARs are nuclear receptor proteins that regulate gene expression, and lanifibranor is designed to target all three PPAR isoforms in a moderately potent manner, with a well-balanced activation of PPARα and PPARδ, and a partial activation of PPARγ.
Inventiva believes that lanifibranor's balanced pan-PPAR binding profile contributes to its observed tolerability in clinical trials and preclinical studies. Notably, lanifibranor is the only pan-PPAR agonist currently in clinical development for MASH. The FDA has granted Breakthrough Therapy and Fast Track designations to lanifibranor for the treatment of MASH, highlighting its potential to address a significant unmet medical need.
NATiV3 Trial Details
The NATiV3 trial is a pivotal Phase 3 clinical trial evaluating the efficacy and safety of lanifibranor in adult patients with MASH. The trial's primary endpoint is to assess the resolution of NASH without worsening of fibrosis or improvement in fibrosis by at least one stage without worsening of NASH. Secondary endpoints include changes in liver histology, metabolic parameters, and other relevant clinical outcomes.
The trial includes a diverse patient population with MASH, reflecting the real-world heterogeneity of the disease. Patients are randomized to receive different doses of lanifibranor or placebo, allowing for a comprehensive evaluation of the drug's efficacy and safety profile.
MASH: An Unmet Medical Need
MASH is a common and progressive chronic liver disease characterized by inflammation and fibrosis. It is often associated with metabolic risk factors such as obesity, type 2 diabetes, and dyslipidemia. Currently, there are limited treatment options available for MASH, highlighting the urgent need for new and effective therapies like lanifibranor.
