Inventiva announced the details of the Phase III clinical trial with its lead drug candidate lanifibranor in NASH following the end-of-phase II meeting with the U.S. Food and Drug Administration (FDA) and the receipt of the Scientific Advice letter from the European Medicines Agency (EMA). The Phase III trial design and clinical strategy have been discussed with both regulatory authorities and the following key points can be confirmed: Seeking of U.S. accelerated approval and EU conditional approval for lanifibranor to be based on a 72-week histology analysis – Inventiva will seek to obtain accelerated approval in the U.S. and conditional approval in the EU for lanifibranor based on a pre-specified histology analysis in approximately 900 patients after 72 weeks establishing a positive benefit-risk ratio. Use of a primary composite endpoint combining NASH resolution and fibrosis improvement – The primary composite endpoint of patients having both NASH resolution and fibrosis improvement of at least one stage will be used for the 72-week histology analysis. The endpoint is designed to predict a significant improvement of prognostic risk and, if met, may support a label for the treatment of NASH and the improvement in liver fibrosis in adult non-cirrhotic NASH patients. During Inventiva’s NATIVE Phase IIb clinical trial, this endpoint was met with statistical significance, including in NASH patients with F2/F3 fibrosis, the patient population that will be included in the Phase III trial, as well as in NASH patients with type two diabetes (TD2M). Endpoints of NASH resolution and no worsening of fibrosis, and improvement of fibrosis with no worsening of NASH will be included as key secondary endpoints. Additional supportive histologic endpoints, non-invasive markers of liver fibrosis and steatohepatitis as well as effects on lipids and insulin resistance will also be evaluated. Named NATIVE3 (NASH lanifibranor Phase 3 trial), the planned trial has been designed as a double-blind, placebo-controlled global pivotal Phase III clinical trial to assess the potential benefit of lanifibranor treatment on liver-related clinical outcomes. Patients will be randomized 1:1:1 to receive lanifibranor (800mg once daily or 1200mg once daily) or placebo. The trial will remain blinded after the pre-specified histological analysis and continue in a total of approximately 2,000 patients until the occurrence of a pre-specified number of adverse liver-related clinical events, including progression to cirrhosis. The trial would be completed on a post-marketing basis in the event that accelerated (U.S.) /conditional (EU) approval is received. Statistical powering of 90% was considered for the sample size calculations of the Phase III clinical trial. The trial preparations are progressing according to schedule and Inventiva plans to initiate the trial in the first half of 2021.