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Inventiva announces positive topline results from the investigator-initiated Phase II clinical trial evaluating lanifibranor in patients with T2D and NAFLD
Lanifibranor 800mg achieved the primary efficacy endpoint demonstrating a 44% reduction of hepatic fat measured by proton magnetic resonance spectroscopy (1H-MRS) following 24 weeks of treatment in patients with nonalcoholic fatty liver disease (NAFLD).
A significantly higher proportion of patients achieved a greater than 30% liver triglyceride reduction as well as NAFLD 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 NAFLD, and ability to improve adipose tissue function (i.e. significant increase in plasma adiponectin and reverse NAFLD).
The study confirmed the favorable safety and tolerability profile of lanifibranor.
Inventiva and Dr. Cusi will host an investors webcast Wednesday, June 14th at 8am EST (details below).
Daix (France), Long Island City (New York, United States), June 13, 2022 –Inventiva (Euronext Paris and Nasdaq: IVA), a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of non-alcoholic steatohepatitis (NASH), mucopolysaccharidoses (MPS) and other diseases with significant unmet medical needs, today announced positive topline results of the clinical study conducted by Dr. Kenneth Cusi from the University of Florida, evaluating lanifibranor in patients with NAFLD and type 2 diabetes mellitus (T2D).
The Phase II clinical trial randomized 38 patients into two arms, with patients receiving placebo or treatment with lanifibranor at 800mg/day for 24 weeks. The study achieved the primary efficacy endpoint with a 44% reduction of Intra Hepatic Triglycerides (IHTG) measured using proton magnetic resonance spectroscopy (1H-MRS) in patients with NAFLD and T2D treated with lanifibranor (800mg/daily) for 24 weeks compared to 12% in the placebo arm. This result is consistent with the Phase IIb NATIVE trial findings, in which lanifibranor demonstrated a statistically significant effect on steatosis reduction as measured by CAP/Fibroscan.1
The study demonstrated a statistically significant higher proportion of patients achieving a greater than 30% liver triglyceride reduction (65% vs. 22%, p =0.008) as well as NAFLD resolution (25% vs. 0%, p = 0.048) defined as IHTG ≤ 5.5% at week 24, with lanifibranor compared to placebo.
In addition, the study demonstrated a significant effect on a series of secondary endpoints including (see tables below), glycemic control (reduction in hemoglobin A1c), atherogenic dyslipidemia (i.e., increase in HDL-C), hepatic insulin action (i.e., fasting hepatic glucose production, hepatic insulin resistance index), insulin-stimulated muscle glucose disposal (i.e., in gold-standard euglycemic insulin clamp studies during high-dose insulin stimulation) and amelioration of the adipose tissue dysfunction with a robust increase in plasma adiponectin. The treatment with lanifibranor 800mg/once daily for 24 weeks was well tolerated, with no safety concerns reported.
Additional secondary endpoints including a series of markers of cardiometabolic health are anticipated to be presented by Dr. Cusi in upcoming scientific conferences and publications.
Dr. Michael Cooreman, M.D., Chief Medical Officer of Inventiva: “The results published today, by showing that lanifibranor reduces intrahepatic triglycerides and contributes to resolve NAFLD in patients with T2D further bolster our robust dataset from our Phase IIb NATIVE study on the efficacy of lanifibranor across the disease spectrum of NAFLD, i.e. histological benefits on NASH resolution and fibrosis improvement as well as an improvement of a broad panel of markers of cardiometabolic health. In addition, we are pleased to see that this study confirms the safety and tolerability of lanifibranor. We want to thank Dr. Cusi for successfully leading this study and for his innovative thinking in designing a clinical trial with these state-of-the-art NITs.”
Dr. Kenneth Cusi, M.D., F.A.C.P., F.A.C.E., 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 is an important study for a drug that has already shown promising results in patients with NASH. Lanifibranor is an insulin-sensitizer with demonstrated effects to reverse steatohepatitis and fibrosis. The positive results of our study on hepatic fat and liver and muscle insulin sensitivity, as well as fat metabolism, within just 24 weeks of treatment confirm the robustness of the mechanism of action of lanifibranor in key tissues, and its potential to manage patients with T2D but also patients with pre-diabetes and obesity. This study brings new and critical results for our patients with T2DM and NASH, which constitute a large proportion of the whole NASH patient population and for whom there are still no approved drugs available. I look forward to publishing more detailed analyses from this exciting study.”
Summary of Week 24 changes in Liver Fat
Full Analysis Set (N=38)
Placebo (n=18) Lani 800mg (n=20) p value
Change in liver fat (intrahepatic TGs) (%)a -12% -44% 0.002 (S)
Proportion of patients with >30% liver fat reduction % b 22% 65% 0.008 (S)
NAFLD resolution (defined as IHTG ≤ 5.5% at Week 24) c 0% 25% 0.048 (S)
a P-value from an Analysis of Covariance. Missing data at Week 24 were imputed by baseline data.
b Missing data at Week 24 were imputed as non-achieving reduction of 30% liver fat reduction.
c Missing data at Week 24 were imputed as non-responders.
Summary of Week 24 changes in glycemic control, insulin sensitivity and cardiometabolic biomarkers
Completers (N=28)
Placebo (n=14) Lani 800mg (n=14)
Glycemic control
Absolute change in HbA1c, % -0.2% -0.9***
Absolute change in Fasting plasma insulin, µU/ml -1.0 -6.7*
Insulin sensitivity
Absolute change in Hepatic Insulin Resistance index -9.5 -30.1*
Absolute change in basal Endogenous glucose production (mg/kgLBM/min) 0.1 -0.5***
Absolute change in muscle insulin-stimulated glucose disposal (mg/kg LBM/min) -0.2 +2.2**
Cardiometabolic biomarkers
Absolute change in HDL-C, mg/dl -0.3 6.3*
Absolute change in Adiponectin, µg/mL -0.2 7.5***
*p≤0.05,**p≤0.01, ***p≤ 0.001 versus placebo
Conference call
Inventiva will host a conference call and webcast with slide presentation on Wednesday, June 14, 2023 at 8:00 am ET (New York time) 2:00 pm CET (Paris time). The conference call and the slides of the presentation will be webcast live at: https://edge.media-server.com/mmc/p/8y8icxm8 and will also be available on Inventiva’s website: Investor Presentations - Inventiva Pharma.
In order to receive the conference access information necessary to join the conference call, it is required to register in advance using the following link:https://register.vevent.com/register/BI22f830c9addc4b7eaf2698bf8c72e1fe. Participants will need to use the conference access information provided in the e-mail received at the point of registering (dial-in number and access code).
About lanifibranor
Lanifibranor, Inventiva’s lead product candidate, is an orally-available small molecule that acts to induce anti-fibrotic, 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 PPARa and PPARd, and a partial activation of PPAR?. 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 NASH. 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 NASH.
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 NASH, mucopolysaccharidoses (“MPS”) and other diseases with significant unmet medical need. The Company benefits from a strong expertise and experience in the domain 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 NASH, a common and progressive chronic liver disease for which there are currently no approved therapies.
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 an
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