Inventiva announces the publication of the results from the investigator-initiated proof-of-concept clinical trial evaluating lanifibranor in patients with T2D and MASLD in the Journal of Hepatology
- As previously reported1, the study met the primary efficacy endpoint for the treatment with lanifibranor 800mg demonstrating a 44% reduction of hepatic fat measured by proton magnetic resonance spectroscopy (1H-MRS) following 24 weeks of treatment in patients with MASLD and T2D
- A significantly higher proportion of patients achieved a greater than 30% liver triglyceride reduction as well as MASLD resolution with lanifibranor compared to placebo
- Lanifibranor treatment significantly improved both hepatic and peripheral insulin sensitivity (i.e. fasting plasma insulin, fasting hepatic glucose production, hepatic insulin resistance index, insulin-stimulated muscle glucose disposal), which translated into better glycemic control (i.e. HbA1c)
- The study met multiple secondary metabolic endpoints confirming the cardiometabolic benefit of lanifibranor in patients with MASLD, and ability to improve adipose tissue function
- The study confirmed the favorable safety and tolerability profile of lanifibranor
Daix (France), New York City (New York, United States), January 29, 2025 – Inventiva (Euronext Paris and Nasdaq: IVA) ("Inventiva" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of metabolic dysfunction-associated steatohepatitis ("MASH") and other diseases with significant unmet medical needs, today announced the publication in Journal of Hepatology, a peer-reviewed scientific journal, of the results from the investigator-initiated clinical study led by Dr. Kenneth Cusi evaluating lanifibranor in patients with type 2 diabetes ("T2D") and Metabolic dysfunction-Associated Liver Disease ("MASLD")1. The clinical trial demonstrated significant improvement of hepatic, muscle and adipose tissue insulin resistance in patients with MASLD and T2D treated with lanifibranor.
The proof-of-concept trial evaluating lanifibranor (800mg/day for 24 weeks) in 38 patients with MASLD and T2D achieved its primary efficacy endpoint. Patients that received treatment with lanifibranor achieved a 44% reduction in intrahepatic triglycerides (IHTG) measured using proton magnetic resonance spectroscopy (1H-MRS), significantly outperforming the placebo group (12%). The treatment with lanifibranor also resulted in a higher proportion of patients achieving over 30% liver triglyceride reduction (65% vs. 22%) and MASLD resolution (25% vs. 0%). Secondary endpoints showed improvements in glycemic control, lipid profiles, hepatic insulin sensitivity, muscle glucose disposal, and adipose tissue function. Lanifibranor was well tolerated with no safety concerns reported.
These findings are consistent with those reported in previous trials with lanifibranor and highlight lanifibranor's potential for managing MASLD, T2D, and related metabolic conditions.
Dr. Kenneth Cusi, Professor of Medicine at the Division of Endocrinology, Diabetes and Metabolism in the Department of Medicine, University of Florida and Principal Investigator of the study, stated: "This study highlights the promising potential with lanifibranor, an insulin-sensitizer that has already shown positive effects in patients with MASH. Within just 24 weeks of treatment, we observed significant improvements in hepatic fat, liver and muscle insulin sensitivity, and fat metabolism, reinforcing the strength of lanifibranor's mechanism of action. These results not only offer hope for managing patients with MASH but also bring crucial insights for patients with T2D and MASH—which we know is a patient population at higher risk of faster progression to advanced fibrotic stages."
Dr. Michael Cooreman, Chief Medical Officer of Inventiva: "We are very happy to see the results of this important clinical study published in the renowned Journal of Hepatology. By demonstrating the effect of lanifibranor on intrahepatic triglycerides reduction and MASLD resolution in patients with type-2 diabetes, this study complements the robust dataset from our Phase IIb NATIVE and Proof-of-Concept LEGEND studies, confirming the potential of lanifibranor as an effective candidate to address the needs of patients suffering from MASH and MASLD. We take this opportunity to express our gratitude and thanks to all patients and investigators, and to Dr. Cusi for successfully leading this study."
Publication details
| Publication title: | "Pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in patients with type 2 diabetes and MASLD." |
| Authors: | Diana Barb, Srilaxmi Kalavalapalli, Eddison Godinez Leiva, Fernando Bril, Philippe Huot-Marchand, Lucile Dzen, Jens T Rosenberg, Jean-Louis Junien, Pierre Broqua, Andrea Ortiz Rocha, Romina Lomonaco, Jean Louis Abitbol, Michael P Cooreman, Kenneth Cusi. |
| Online version: | doi: 10.1016/j.jhep.2024.12.045. Epub ahead of print. PMID: 39824443. |
About lanifibranor
Lanifibranor, Inventiva's lead product candidate, is an orally-available small molecule that acts to induce antifibrotic, anti-inflammatory and beneficial vascular and metabolic changes in the body by activating all three peroxisome proliferator-activated receptor ("PPAR") isoforms, which are well-characterized nuclear receptor proteins that regulate gene expression. Lanifibranor is a PPAR agonist that 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. While there are other PPAR agonists that target only one or two PPAR isoforms for activation, lanifibranor is the only pan-PPAR agonist in clinical development for the treatment of MASH. Inventiva believes that lanifibranor's moderate and balanced pan-PPAR binding profile contributes to the favorable tolerability profile that has been observed in clinical trials and pre-clinical studies to date. The FDA has granted Breakthrough Therapy and Fast Track designation to lanifibranor for the treatment of MASH.
About Inventiva
Inventiva is a clinical-stage biopharmaceutical company focused on the research and development of oral small molecule therapies for the treatment of patients with MASH and other diseases with significant unmet medical need. The Company benefits from a strong expertise and experience in the field of compounds targeting nuclear receptors, transcription factors and epigenetic modulation. Inventiva is currently advancing one clinical candidate, has a pipeline of two preclinical programs and continues to explore other development opportunities to add to its pipeline.
Inventiva's lead product candidate, lanifibranor, is currently in a pivotal Phase III clinical trial, NATiV3, for the treatment of adult patients with MASH, a common and progressive chronic liver disease.
Inventiva's pipeline also includes odiparcil, a drug candidate for the treatment of adult MPS VI patients. As part of Inventiva's decision to focus clinical efforts on the development of lanifibranor, it suspended its clinical efforts relating to odiparcil and is reviewing available options with respect to its potential further development. Inventiva is also in the process of selecting a candidate for its Hippo signaling pathway program.
The Company has a scientific team of approximately 90 people with deep expertise in the fields of biology, medicinal and computational chemistry, pharmacokinetics and pharmacology, and clinical development. It owns an extensive library of approximately 240,000 pharmacologically relevant molecules, approximately 60% of which are proprietary, as well as a wholly owned research and development facility.
Inventiva is a public company listed on compartment B of the regulated market of Euronext Paris ((ticker: IVA, OTC:IVEVF) and on the Nasdaq Global Market in the United States (ticker: IVA). www.inventivapharma.com
Contacts
| Inventiva Pascaline Clerc EVP, Strategy and Corporate Affairs [email protected] +1 202 499 8937 | Brunswick Group Tristan Roquet Montegon / Aude Lepreux / Julia Cailleteau Media relations [email protected] +33 1 53 96 83 83 | Westwicke, an ICR Company Patricia L. Bank Investor relations [email protected] +1 415 513 1284 |
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