Inventiva announces changes to the clinical development of
lanifibranor, including plans for a new Phase III trial in patients
with NASH and compensated cirrhosis
- Proposed changes are expected to be beneficial to the
lanifibranor clinical program by reducing the number of biopsies
and the trial duration, eventually offering all patients in the
trial access to treatment and potentially expanding the addressable
patient population to patients with NASH and compensated
cirrhosis
- Confirmatory trial of lanifibranor clinical benefits, which was
initially planned to be evaluated in Part 2 of NATiV3 trial in
patients with NASH and F2/F3 fibrosis, is now planned to be
evaluated in a new Phase III trial in patients with NASH and
compensated cirrhosis in place of the previously planned Part 2 of
the NATiV3 trial
- The ongoing Part 1 of the NATiV3 trial continues as planned
and, if successful, is expected to provide the necessary data to
support NDA submission for accelerated approval, based on liver
histological endpoints; expected enrollment for Part 1 remains on
track with last patient first visit expected to be completed H2
2023
- Approximately 200 screen-failed patients from Part 1 of
the NATiV3 trial are expected to be included in a new 72-week
exploratory cohort aimed at generating results based on
non-invasive tests and contributing to the regulatory safety
database
- All patients enrolled in Part 1 of the NATiV3 trial and the
exploratory cohort could have access to lanifibranor treatment by
being offered to participate in a new 48-week active treatment
extension study
- The results of the new planned Phase III in patients with NASH
and compensated cirrhosis, if successful, are expected to support
the submission for FDA full approval and expand the addressable
patient population beyond patients with F2 and F3 fibrosis to
include patients with NASH and compensated cirrhosis
Daix (France), Long
Island City (New York, United States),
January 4,
2023 – Inventiva (Euronext Paris and
Nasdaq: IVA) (the “Company”), a clinical-stage biopharmaceutical
company focused on the development of oral small molecule therapies
for the treatment of patients with non-alcoholic steatohepatitis
(“NASH”), mucopolysaccharidoses (“MPS”) and other diseases with
significant unmet medical needs, today announced that, following a
consultation with the U.S. Food and Drug Administration (“FDA”),
Inventiva has decided to modify the clinical development plan of
lanifibranor for the treatment of NASH. Inventiva’s request for a
consultation with the FDA followed a public communication by the
FDA1 suggesting that an alternative approach to seek full approval
in patients with NASH could be considered upon submission of
positive results of a Phase III trial using a histology surrogate
endpoint in patients with NASH and a Phase III clinical outcome
trial in patients with NASH and compensated cirrhosis. The
Company’s proposed changes to the NATiV3 trial are designed to
align with the alternative regulatory approach and are expected to
be beneficial to the overall lanifibranor clinical program by 1)
reducing the number of biopsies a patient undergoes during the
trial from three to two, 2) reducing the trial duration a patient
has to consent to from 7 years to 72 weeks, 3) offering all
patients in the trial access to a lanifibranor treatment for at
least 48 weeks by allowing them to enter into a new active
treatment extension study, and 4) potentially expanding the
addressable patient population to include patients with NASH and
compensated cirrhosis.
The Company continues to anticipate submission
of a new drug application (“NDA”) to the FDA for accelerated
approval with such planned submission based on liver histological
endpoints of approximately 900 patients treated over a 72-week
period. A placebo-controlled exploratory cohort is anticipated to
be added in parallel to Part 1 of the NATiV3 trial and will include
approximately 200 patients with NASH and fibrosis who are not
eligible for Part 1 (screen failures). The Company anticipates that
this exploratory cohort may allow the generation of additional
results using non-invasive tests and contribute to the safety
database requirement to support the planned submission for
potential accelerated approval.
Under the newly planned trial design, the
original Part 2 of the NATiV3 trial, a clinical outcome trial that
was previously planned to be conducted in approximately 2,000
patients with F2 and F3 fibrosis for a maximum period of seven
years will be replaced by a placebo-controlled Phase III outcome
trial which will be event driven and is expected to last
approximately three years. The Phase III outcome trial is expected
to randomize approximately 800 patients with NASH and compensated
cirrhosis.
If the results of the outcome trial in patients
with NASH and compensated cirrhosis are positive, the Company
anticipates they will support the submission of an NDA to the FDA
for full approval and the potential expansion of the addressable
patient population beyond patients with F2 and F3 fibrosis to
include patients with NASH and compensated cirrhosis, a patient
population at an increased risk of liver-related morbidity and
mortality and for which the anti-fibrotic properties of
lanifibranor could potentially prevent worsening of the disease.
Lanifibranor has been granted both Fast Track and Breakthrough
Therapy designations for the treatment of NASH, and the FDA
confirmed last year that the Fast Track designation is also
applicable to the treatment of NASH for patients with compensated
cirrhosis.
The Company does not expect these trial design
changes to have a significant impact on the funds originally
anticipated to be needed to potentially secure accelerated approval
in the U.S. or conditional approval in the EU based on the new
trial design.
Michael
Cooreman,
M.D., Chief
Medical Officer of Inventiva,
commented: “This is a promising evolution for our
lanifibranor clinical development program. Not only are Inventiva’s
changes to the trial design expected to provide an opportunity for
patients enrolled in the placebo arm to access a lanifibranor
treatment arm, but also the changes are designed to reduce the
number of biopsies. We believe these changes provide an opportunity
to support the anticipated timeline to seek accelerated approval
and potentially bring a treatment option to a larger population
which could include patients with NASH and compensated
cirrhosis.”
Prof. Arun Sanyal, M.D.,
Director of the
Stravitz-Sanyal Institute for
Liver Disease and Metabolic Health,
Virginia Commonwealth University and co-principal
investigator of the NATiV3 Phase III clinical
trial, stated: “This revised clinical
trial design has been built on the latest thinking in the field. I
believe that these changes to the program with an amended NATiV3
and Phase III trial in patients with compensated cirrhosis will
reinforce the scientific rigour of the development program as it
will now include a broader patient population in dire need of
treatment options.”
Prof. Sven Francque, M.D., Ph.D.,
Antwerp University Hospital and co-principal investigator of the
NATiV3 Phase III clinical trial, said: “Lanifibranor has
demonstrated a significant effect on the composite histological
endpoint in the NATIVE Phase IIb trial. Given lanifibranor’s
mechanism of action and the effects demonstrated on the broad
spectrum of the disease, including its anti-fibrotic effect, I
believe including patients with NASH and compensated cirrhosis in
the program is extremely relevant.”
Donna Cryer, President and CEO of the
Global Liver Institute, said: “Patients
and caregivers commend Inventiva for making these changes in
consultation with regulators. We believe limiting the number of
biopsies and giving patients, both randomized and placebo, access
to a treatment arm are invaluable measures for patients suffering
with NASH and who still do not have access to any approved
treatment options today.”
Enrolment for Part 1 of the NATiV3 trial remains
on track, with the last patient first visit expected to take place
in the second half of 2023.
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 most-advanced 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, 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 80 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 C 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 Clerc VP of Global External
Affairs media@inventivapharma.com +1 240 620 9175 |
Brunswick Group Laurence Frost / Tristan Roquet
Montegon / Aude Lepreux Media relations
inventiva@brunswickgroup.com +33 1 53 96 83 83 |
Westwicke,
an ICR Company Patricia L. Bank Investor relations
patti.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 Part 1 of the
NATiV3 Phase III clinical trial, and the planned new Phase III
clinical trial and 48-week active treatment extension study with
lanifibranor in NASH, 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 addressable patient population,
the potential therapeutic benefits of lanifibranor for patients
with F2 and F3 fibrosis, NASH and compensated cirrhosis, regulatory
submissions and approvals, the benefit of having received the FDA’s
Breakthrough Therapy and Fast Track designation for lanifibranor in
the treatment of NASH or the impact thereof on Inventiva’s ability
to obtain regulatory approval, the expectation that the revised
Phase III clinical trial NATiV3 and new Phase III clinical trial
will facilitate patient enrolment, the effect of the changes to the
NATiV3 Phase III clinical trial on the results and timeline of the
trial, that the trial is expected to provide the necessary data to
support NDA submission for accelerated approval and the likelihood
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based on management's beliefs. These statements reflect such views
and assumptions prevailing as of the date of the 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 statements. Future events
are difficult to predict and may depend 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 anticipated, that product candidates
will receive the necessary regulatory approvals, or that any of the
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on their expected timeline, or at all. Actual results may turn out
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including that Inventiva is a clinical-stage company with no
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claims, Inventiva may encounter substantial delays in its clinical
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of Inventiva to recruit and retain patients in clinical studies,
enrolment and retention of patients in clinical trials is an
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difficult or rendered impossible by multiple factors outside
Inventiva's control, Inventiva's product 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 competition and Inventiva’s
business, and preclinical studies and clinical development programs
and timelines, its financial condition and results of operations
could be materially and adversely affected by the current COVID-19
pandemic and geopolitical events, such as the conflict between
Russia and Ukraine, related sanctions and related impacts and
potential impacts on the initiation, enrolment and completion of
Inventiva’s clinical trials on anticipated timelines, and
macroeconomic conditions, including global inflation and uncertain
financial markets. Given these risks and uncertainties, no
representations are made as to the accuracy or fairness of such
forward-looking statements, forecasts and estimates. Furthermore,
forward-looking statements, forecasts and estimates only speak as
of the date of this press release. Readers are cautioned not to
place undue reliance on any of these forward-looking
statements.
Please refer to the Universal Registration
Document for the year ended December 31, 2021 filed with the
Autorité des Marchés Financiers on March 11, 2022, the Annual
Report on Form 20-F for the year ended December 31, 2021 filed with
the Securities and Exchange Commission on March 11, 2022 and the
financial report for the first half of 2022 filed with the
Securities and Exchange Commission on September 22, 2022 for
additional information in relation to such factors, risks and
uncertainties.
All information in this press release is as of
the date of the release. Except as required by law, Inventiva has
no intention and is under no obligation to update or review the
forward-looking statements referred to above.
1 FDA Webcast. “Regulatory Perspectives for Development of Drugs
for Treatment of NASH.” January 29, 2021. Available at
https://www.fda.gov/drugs/news-events-human-drugs/regulatory-perspectives-development-drugs-treatment-nash-01292021-01292021
- Inventiva - PR - Changes clinical development of lanifibranor -
EN - 01 04 2023
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