Scientific and clinical resources for healthcare professionals

Inventiva Medical Affairs

Inventiva Medical Affairs supports scientific exchange and provides resources for healthcare professionals, researchers, and qualified stakeholders interested in MASH and lanifibranor.

About MASH

MASH (metabolic dysfunction-associated steatohepatitis) is a progressive liver disease defined by liver steatosis, inflammation, hepatocellular injury, and fibrosis.

But MASH is not solely a liver disease. Rooted in metabolic dysfunction, it is strongly linked to cardiometabolic comorbidities such as type 2 diabetes mellitus and obesity, which increase the risk of cardiovascular events and all-cause mortality and accelerate progression to advanced fibrosis.

Without intervention, MASH often leads to life-threatening complications including cirrhosis, liver failure, and hepatocellular carcinoma. For many, it leads to the need for a liver transplant; MASH is the leading cause of liver transplants among women in the U.S. and is projected to soon become the leading cause for all liver transplantation.

Current therapeutic options do not fully address MASH’s multifactorial pathogenesis, creating a critical need for a treatment that simultaneously targets intrahepatic fibrosis progression and the extrahepatic manifestations of metabolic dysfunction. This is particularly urgent for the large population of patients with F2-F3 fibrosis who are at high risk of rapid progression to cirrhosis.

About Lanifibranor

By treating MASH at its source in the liver while also addressing its systemic effects, lanifibranor reflects a scientifically grounded approach to a complex, multisystem disease.

Lanifibranor is an oral therapy designed to simultaneously activate all three subtypes of “peroxisome proliferator-activated receptors,” or PPARs. PPARs are ligand-activated nuclear transcription factors that serve as master regulators of metabolic homeostasis, governing lipid oxidation, glucose metabolism, inflammatory signaling, and fibrogenic activity.

Through balanced activation across all three PPAR isoforms, lanifibranor is designed to achieve receptor engagement without tolerability limitations associated with selective or partial PPAR agonism.

Lanifibranor seeks to restore metabolic balance at the source as well as directly target inflammation and fibrosis.

This mechanistic rationale, supported by Phase 2 clinical evidence, is reflected in the FDA’s Breakthrough Therapy designation for lanifibranor.

View Press Release

How Lanifibranor Works

Clinical Trials

Inventiva’s clinical program is built on the scientific understanding that MASH requires a therapy capable of addressing its full biological complexity.

Lanifibranor, a pan-PPAR agonist, is designed to reduce liver fat, resolve inflammation, and reverse fibrosis through a once-daily oral therapy.

NATiV3 Clinical Trial

NATiV3 Clinical Trial

Inventiva is currently conducting NATiV3, a global Phase 3 study to confirm the long-term safety and effectiveness of lanifibranor. The trial is underway at more than 350 clinical sites across 22 countries and completed enrollment in April 2025. Learn more.

Participants in the NATiV3 trial are adults with biopsy-confirmed MASH and moderate-to-advanced fibrosis (F2–F3). The trial’s results are intended to support accelerated FDA approval and conditional EMA approval. Topline results are anticipated in the last quarter of 2026.

NATiV3 clinical trial overview

Trial Design

NATiV3 trial design diagram

Clinical Trial Sites

Clinical trial sites map Clinical Trials.gov

Previous Clinical Trials

The completed NATIVE study evaluated lanifibranor in patients with biopsy-confirmed, noncirrhotic NASH. The results, published in The New England Journal of Medicine, demonstrated that lanifibranor is a potential best-in-disease therapy.

Read the Results
NATIVE (Phase 2b) 24-weeks View Press Release

Patient Population/Inclusion Criteria

Biopsy-proven MASH; SAF scores:
Steatosis (1-3), Activity (3-4), Fibrosis (<4)

Dose Cohorts & Patients (N)

800mg (N=83), 1200mg (N=83), Placebo (N=81); Total N=247

Efficacy Results

1200mg: 45% MASH resolution (p<0.001) and 42% fibrosis improvement (p=0.013). Resolution & improvement: 31% (p=0.003)

AEs/Safety

Mean weight gain: 2.7kg (3.1%) at 1200mg. Peripheral edema: 8.4% (1200mg) vs 2.5% (Placebo). Most mild/moderate

LEGEND (Phase 2) 24-weeks View Press Release

Patient Population/Inclusion Criteria

Patients with MASH and poorly controlled type 2 diabetes (T2D)

Dose Cohorts & Patients (N)

Lanifibranor 800mg + Empagliflozin 10mg vs. Lanifibranor mono vs. placebo; (N=~20 per group in interim)

Efficacy Results

Met Primary: Significant reduction in hepatic steatosis (MRI-PDFF) vs placebo (p=0.002)

AEs/Safety

Well tolerated; combo designed to mitigate PPAR-γ related weight gain via SGLT2i

Cusi Study (PI-led) 24-weeks View Press Release

Patient Population/Inclusion Criteria

Type 2 diabetes patients with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD)

Dose Cohorts & Patients (N)

800mg once daily (N=38)

Efficacy Results

Significant improvement in hepatic, muscle, and adipose tissue insulin resistance (published J. Hepatology 2025)

AEs/Safety

N/A

Publications

EASL2026: Lanifibranor-Induced Histological and Cardiometabolic Improvements in MASH Are Independent of Weight Change and Associated With Adiponectin Induction

View Poster

EASL 2026: Ultrastructural Assessment of Liver Sinusoidal Endothelial Cell Capillarisation in Metabolic Dysfunction-Associated Steatotic Liver Disease and Its Modulation by Lanifibranor

View Poster

MASH-TAG 2026: Comparative Modulation of Adiponectin Across Select Therapeutics in Clinical Development for MASH with Fibrosis Identifies Lanifibranor as a Differentiated Metabolic Modulator

View Poster

Sign Up for Updates

If you are interested in receiving updates about the lanifibranor clinical trial program please share your contact details here.