Inventiva announces changes to the clinical development of lanifibranor, including plans for a new Phase III trial in patients with NASH and compensated cirrhosis.

Inventiva’s request for a consultation with the FDA followed a public communication by the FDA suggesting that an alternative approach to seek full approval in patients with NASH could be considered upon submission of positive results of a Phase III trial using a histology surrogate endpoint in patients with NASH and a Phase III clinical outcome trial in patients with NASH and compensated cirrhosis.

The Company’s proposed changes to the NATiV3 trial are designed to align with the alternative regulatory approach and are expected to be beneficial to the overall lanifibranor clinical program by 1) reducing the number of biopsies a patient undergoes during the trial from three to two, 2) reducing the trial duration a patient has to consent to from 7 years to 72 weeks, 3) offering all patients in the trial access to a lanifibranor treatment for at least 48 weeks by allowing them to enter into a new active treatment extension study, and 4) potentially expanding the addressable patient population to include patients with NASH and compensated cirrhosis.

The Company continues to anticipate submission of a new drug application (“NDA”) to the FDA for accelerated approval with such planned submission based on liver histological endpoints of approximately 900 patients treated over a 72-week period . A placebo-controlled exploratory cohort is anticipated to be added in parallel to Part 1 of the NATiV3 trial and will include approximately 200 patients with NASH and fibrosis who are not eligible for Part 1 (screen failures). The Company anticipates that this exploratory cohort may allow the generation of additional results using non-invasive tests and contribute to the safety database requirement to support the planned submission for potential accelerated approval.

Under the newly planned trial design, the original Part 2 of the NATiV3 trial, a clinical outcome trial that was previously planned to be conducted in approximately 2,000 patients with F2 and F3 fibrosis for a maximum period of seven years will be replaced by a placebo-controlled Phase III outcome trial which will be event driven and is expected to last approximately three years. The Phase III outcome trial is expected to randomize approximately 800 patients with NASH and compensated cirrhosis. If the results of the outcome trial in patients with NASH and compensated cirrhosis are positive, the Company anticipates they will support the submission of an NDA to the FDA for full approval and the potential expansion of the addressable patient population beyond patients with F2 and F3 fibrosis to include patients with NASH and compensated cirrhosis, a patient population at an increased risk of liver-related morbidity and mortality and for which the anti-fibrotic properties of lanifibranor could potentially prevent worsening of the disease.

Lanifibranor has been granted both Fast Track and Breakthrough Therapy designations for the treatment of NASH, and the FDA confirmed last year that the Fast Track designation is also applicable to the treatment of NASH for patients with compensated cirrhosis.

Prof. Arun Sanyal, M.D., Director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University and co-principal investigator of the NATiV3 Phase III clinical trial, stated: “This revised clinical trial design has been built on the latest thinking in the field. I believe that these changes to the program with an amended NATiV3 and Phase III trial in patients with compensated cirrhosis will reinforce the scientific rigour of the development program as it will now include a broader patient population in dire need of treatment options.” .