Inventiva completes patient visits in NATiV3 MASH Phase 3 trial
Inventiva has announced that the last patient has completed their final 72-week visit in NATiV3, the Phase 3 pivotal trial of lanifibranor in metabolic dysfunction-associated steatohepatitis (MASH). The milestone clears the path for a topline data readout the company expects to deliver before the end of 2026.
The trial enrolled 1,009 adults with biopsy-proven, non-cirrhotic MASH and F2/F3 liver fibrosis, the main cohort, alongside an exploratory cohort of 410 patients covering F1 through F4 fibrosis stages. The randomised, double-blind, placebo-controlled design evaluated lanifibranor at 800mg and 1,200mg daily over 72 weeks, with dual histological primary endpoints: MASH resolution and at least one stage of fibrosis improvement. Patients also had the option to continue into a 48-week open-label extension, which will generate longer-term safety data.
The drug and its mechanism
Lanifibranor is an orally administered small molecule that acts as a pan-PPAR agonist, activating all three peroxisome proliferator-activated receptor isoforms, alpha, delta, and gamma, in a moderately balanced manner. Inventiva positions this broad activation profile as a distinguishing feature, arguing that targeting all three isoforms simultaneously addresses both the hepatic and metabolic dimensions of MASH more comprehensively than agents that hit only one or two isoforms. The FDA has granted lanifibranor both Breakthrough Therapy and Fast Track designation, reflecting the agency's view of the unmet need in noncirrhotic MASH with significant fibrosis.
Andrew Obenshain, chief executive of Inventiva, said the last-patient, last-visit milestone was "important for Inventiva and for the development of lanifibranor in noncirrhotic MASH," and that the company looks forward to reporting topline results later this year.
Co-principal investigator Prof. Sven Francque, of the University of Antwerp, described the completion of NATiV3 as a milestone for the MASH field more broadly, citing the pan-PPAR mechanism's potential to address the "complexity of MASH disease" through interconnected intrahepatic and extrahepatic pathways.
Market context and competitive landscape
MASH has become one of the most closely watched therapeutic areas in hepatology, with Madrigal Pharmaceuticals' resmetirom (Rezdiffra) having received FDA approval in March 2024 as the first drug specifically indicated for MASH with fibrosis. That approval established histological dual endpoints, MASH resolution and fibrosis improvement, as the regulatory template, which NATiV3 is designed to mirror. A further wave of late-stage programmes is advancing, including candidates from Novo Nordisk and AstraZeneca, meaning lanifibranor would enter a rapidly evolving competitive environment if approved.
Lanifibranor's pan-PPAR profile differentiates it mechanistically from resmetirom, a thyroid hormone receptor beta agonist, though head-to-head comparative data do not exist. Physicians and payers will likely scrutinise the NATiV3 dataset for the magnitude of fibrosis regression and the safety signal, particularly cardiovascular and fluid-retention effects historically associated with PPARgamma activation, when assessing where the drug might sit in future treatment algorithms.
If topline results are positive, Inventiva anticipates submitting a regulatory application in H1 2027 and targeting a potential US launch in 2028, subject to FDA approval. The company is dual-listed on Euronext Paris and Nasdaq under the ticker IVA. Investors will next hear from management on 28 September 2026, when the company publishes its H1 2026 financial results and hosts a conference call.