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 |
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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 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 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 oncology development 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, ISIN: FR0013233012) and on the Nasdaq Global Market in the
United States (ticker: IVA). www.inventivapharma.com
Contacts
Inventiva Pascaline ClercVP of Global External
Affairsmedia@inventivapharma.com +1 240 620
9175 |
Brunswick GroupTristan Roquet Montegon /Aude
Lepreux /Matthieu BenoistMedia
relationsinventiva@brunswickgroup.com +33 1 53 96 83
83 |
Westwicke, an ICR CompanyPatricia L. BankInvestor
relationspatti.bank@westwicke.com
+1 415 513-1284 |
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Important Notice
This press release contains “forward-looking
statements” within the meaning of the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995. All statements,
other than statements of historical facts, included in this press
release are forward-looking statements. These statements include,
but are not limited to, forecasts and estimates with respect to
Inventiva’s pre-clinical programs and clinical trials, including
design, duration, timing, recruitment costs, screening and
enrolment for those trials, including the ongoing NATiV3 Phase III
clinical trial with lanifibranor in NASH and the LEGEND Phase IIa
combination trial with lanifibranor and empagliflozin in patients
with NASH and type 2 diabetes, potential development of and
regulatory pathway for odiparcil, clinical trial data releases and
publications, the information, insights and impacts that may be
gathered from clinical trials, the potential therapeutic benefits,
including reduction of IHTG, reduction of steatosis, improvement of
hepatic and peripheral insulin sensitivity and improvement of a
panel of markers of cardiometabolic health, reduction in fasting
plasma glucose, atherogenic dyslipidemia, hepatic insulin action,
insulin-stimulated muscle glucose disposal, reversal of adipose
tissue dysfunction with a robust increase in plasma adiponectin,
and reversal of steatohepatitis and fibrosis, of Inventiva’s
product candidates, including lanifibranor, the publication by Dr.
Cusi of additional secondary endpoints, including a series of
markers of cardiometabolic health and more detailed analyses,
potential regulatory submissions and approvals, and Inventiva’s
pipeline and preclinical and clinical development plans, future
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statements and involve known and unknown risks and uncertainties
that could cause future results, performance or future events to
differ materially from those expressed or implied in such
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upon factors that are beyond Inventiva's control. There can be no
guarantees with respect to pipeline product candidates that the
clinical trial results will be available on their anticipated
timeline, that future clinical trials will be initiated as
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timeline, or at all. Actual results may turn out to be materially
different from the anticipated future results, performance or
achievements expressed or implied by such statements, forecasts and
estimates, due to a number of factors, including that Inventiva is
a clinical-stage company with no approved products and no
historical product revenues, Inventiva has incurred significant
losses since inception, Inventiva has a limited operating history
and has never generated any revenue from product sales, Inventiva
will require additional capital to finance its operations, in the
absence of which, Inventiva may be required to significantly
curtail, delay or discontinue one or more of its research or
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otherwise capitalize on its business opportunities and may be
unable to continue as a going concern, Inventiva's future success
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are not necessarily predictive of future results and the results of
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changes to the clinical development plan for lanifibranor for the
treatment of NASH may not be realized and may not support the
approval of a New Drug Application, Inventiva may encounter
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candidates may cause adverse drug reactions or have other
properties that could delay or prevent their regulatory approval,
or limit their commercial potential, Inventiva faces substantial
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Please refer to the Universal Registration Document for the year
ended December 31, 2022 filed with the Autorité des Marchés
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All information in this press release is as of the date of the
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1 Lanifibranor treatment improves hepatic steatosis in
patients with NASH, evaluated by histological grading and
Controlled Attenuation Parameter (CAP); Cooreman MP, Abedelmalek
MP, Baudin, Huot-Marchand, Dzen, Fournier, Junien, Broqua,
Francque;
https://inventivapharma.com/wp-content/uploads/2021/11/LANIFIBRANOR-TREATMENT-IMPROVES-HEPATIC...pdf
- Inventiva - PR - Cusi Lani - Topline Results - EN -
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