Inventiva announces the initiation of its pivotal Phase III
clinical trial evaluating lanifibranor in NASH
- Activation of first clinical sites and start of patient
screening
- The two-part NATiV3 Phase III clinical trial will evaluate the
long-term efficacy and safety of lanifibranor in adult patients
with non-cirrhotic NASH and F2/F3 stage of liver fibrosis
- The primary endpoint of the trial’s part 1 will evaluate the
response to the treatment defined by both resolution of NASH and
fibrosis improvement of at least one stage
- Publication of topline results of part 1 of the trial is
expected for H2 2024
- Based on the results of part 1 of the NATiV3 trial, Inventiva
intends to seek U.S. accelerated approval and EU conditional
approval for lanifibranor
Daix (France), September 8,
2021 – 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 need, today announced the
initiation of its NATiV3 Phase III clinical trial evaluating
lanifibranor for the treatment of NASH.1 The first clinical trial
sites have been activated in the United States and first patients
have been screened. In addition, more than 330 sites across 25
countries have already been qualified2 of which more than a third
in the United States.
NATiV3 (NASH lanifibranor Phase 3 trial) is a
randomized, double-blind, placebo-controlled, Phase III clinical
trial evaluating the long-term efficacy and safety of lanifibranor
(800mg/daily and 1200mg/daily) in adult patients with biopsy-proven
non-cirrhotic NASH and F2/F3 stage of liver fibrosis.
The clinical trial includes two parts: a 72-week
treatment of approximately 900 patients to assess the effect of
lanifibranor on the primary composite endpoint of NASH resolution
and fibrosis improvement of at least one stage and on the key
secondary endpoints of NASH resolution with no worsening of
fibrosis, and improvement of fibrosis with no worsening of NASH
(part 1). Following part 1, the trial will remain blinded and
continue in approximately 2,000 patients to evaluate the effect of
lanifibranor on delaying NASH disease progression, measured by a
composite endpoint that includes progression to cirrhosis,
liver-related clinical outcome events, and all-cause death, as
compared to the placebo control arm (part 2).
The primary composite endpoint of part 1 of the
NATiV3 Phase III clinical trial is identical to the composite
efficacy endpoint used in Inventiva’s NATIVE Phase IIb clinical
trial which was met by both lanifibranor doses with statistical
significance, including in NASH patients with F2/F3 fibrosis and
NASH patients with type 2 diabetes (T2DM).
The last visit of the last patient enrolled in
part 1 of the NATiV3 Phase III clinical trial is planned for the
first half of 2024, with the publication of the topline results of
part 1 of the trial expected for the second half of 2024.
If part 1 of the NATiV3 trial is successful,
Inventiva intends to seek accelerated approval in the United States
and conditional approval in the EU for lanifibranor. The study will
also provide a comprehensive safety data set to evaluate, in
combination with the therapeutic efficacy data, the benefit/risk
ratio of lanifibranor therapy as the basis for full regulatory
approval in both the United States and the EU following completion
of part 2 of the trial.
Prof. Sven Francque, M.D., Ph.D.,
Antwerp University Hospital and co-principal investigator of the
NATiV3 Phase III clinical trial, said: “The start of the
pivotal Phase III clinical trial with lanifibranor represents a key
milestone in its development, as well as for the patient community
and the NASH field more generally. During the NATIVE Phase IIb
trial, 21% and 31% of patients in the lanifibranor 800mg/day and
1200mg/day dose groups respectively achieved the Phase III primary
composite endpoint after only 24 weeks of treatment compared to 7%
in the placebo arm. These results give us great confidence in the
NATiV3 trial and the potential of lanifibranor.”
Prof. Arun Sanyal, M.D., Virginia
Commonwealth University and co-principal
investigator of the NATiV3 Phase III clinical
trial, added: “As an orally-available
small molecule and the only pan-PPAR agonist currently in clinical
development for the treatment of NASH, lanifibranor has shown a
unique and very promising mechanism of action thus far. Based on
its favorable safety profile and efficacy results observed in the
previous Phase IIb trial, we are very excited about the potential
benefits lanifibranor could bring to patients.”
Dr. Michael Cooreman, Chief Medical
Officer of Inventiva, commented: “We are pleased to
announce the start of our highly-anticipated NATiV3 Phase III
clinical trial in NASH. While NASH patients continue to suffer from
this devastating disease without any approved treatment available
today, our entire team is fully committed to addressing this
critical, unmet medical need. We have decided to replicate several
key elements of the previous Phase IIb trial, including using the
same patient enrollment screening criteria, and have developed a
central biopsy review process in alignment with regulatory
authorities. We believe in the therapeutic potential of
lanifibranor, which should put us in a strong position to seek
accelerated approval in the US and conditional marketing
authorization in the EU.”
The initiation of the NATiV3 trial follows the
publication of positive results from Inventiva’s NATIVE Phase IIb
clinical trial with lanifibranor in NASH in June 2020 as well as
its designation as Breakthrough Therapy by the U.S. Food and Drug
Administration (FDA) in October 2020.
About the NATiV3 Phase III
trial
The two-part NATiV3 (NASH lanifibranor Phase 3
trial) clinical trial is a randomized, double-blind,
placebo-controlled trial, evaluating the long-term efficacy and
safety of lanifibranor in adult patients with non-cirrhotic NASH
and F2/F3 stage of liver fibrosis.
Patients will be randomized 1:1:1 in placebo and
treatment arms (800mg/daily or 1200mg/daily of lanifibranor) and
stratified based on their fibrotic stage (F2 and F3) as well as
presence or absence of type 2 diabetes (T2DM).
Part 1 of the trial will assess the effect of
lanifibranor (800mg/daily and 1200mg/daily) compared to placebo on
the primary composite endpoint of NASH resolution and improvement
of fibrosis of at least one stage. The key secondary enpoints
include NASH resolution without worsening of fibrosis as well as
improvement of fibrosis and no worsening of NASH. Part 1 is
expected to recruit approximately 900 patients selected upon liver
biopsy and enrolled in approximately 300 sites, with the objective
to obtain accelerated approval from the Food and Drug
Administration (FDA) in the United States and conditional approval
from the European Medicines Agency (EMA) in the EU for lanifibranor
based on a pre-specified histology analysis after 72 weeks of
treatment. The last visit of the last patient for part 1 is
scheduled for the first half of 2024 and the publication of topline
results for the second half of 2024.
Part 2 will follow the 72-week histology
analysis and will assess the effect of lanifibranor (800mg/daily
and 1200mg/daily) compared to placebo on delaying NASH disease
progression measured by a composite endpoint that includes
progression to cirrhosis, liver-related clinical outcome events,
and all-cause death. In part 2, the trial will remain blinded and
continue in a total of approximately 2,000 patients until the
occurrence of a pre-specified number of liver-related clinical
events. The trial would be completed on a post-marketing basis in
the event that accelerated (U.S.) / conditional (EU) approval is
received. Based on the results from part 2, Inventiva plans to seek
full regulatory approval for lanifibranor in both the United States
and the EU.
In addition to the key primary and secondary
endpoints, the impact of lanifibranor on biomarkers of metabolic
health will be evaluated as part of the trial. The occurrence of
Major Adverse Cardiovascular Events (MACE), such as myocardial
infarction and stroke, will also be evaluated as an exploratory
efficacy endpoint and to establish the safety profile of
lanifibranor.
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. 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 NASH
Non-alcoholic steatohepatitis (NASH) is a
serious liver disease characterized by excessive fat accumulation
in the liver, chronic inflammation and tissue injury (hepatitis),
resulting in progressive fibrosis that can lead to cirrhosis, and
subsequently portal hypertension, liver insufficiency and potential
liver cancer. The prevalence of NASH is rapidly increasing globally
in parallel to the growing epidemics of obesity and type 2 diabetes
(T2DM); correspondingly, the proportion and number of liver
transplants attributable to NASH has expanded considerably in the
past years. To date, there are still no drug therapies approved for
the treatment of NASH.
About Inventiva
Inventiva is a clinical-stage biopharmaceutical
company focused on the development of oral small molecule therapies
for the treatment of NASH, MPS and other diseases with significant
unmet medical need.
Leveraging its expertise and experience in the
domain of compounds targeting nuclear receptors, transcription
factors and epigenetic modulation, Inventiva is currently advancing
two clinical candidates, as well as a deep pipeline of earlier
stage programs.
Lanifibranor, its lead product candidate, is
being developed for the treatment of patients with NASH, a common
and progressive chronic liver disease for which there are currently
no approved therapies. Inventiva recently announced positive
topline data from its Phase IIb clinical trial evaluating
lanifibranor for the treatment of patients with NASH and obtained
Breakthrough Therapy and Fast Track designation for lanifibranor in
the treatment of NASH.
Inventiva is also developing odiparcil, a second
clinical stage asset, for the treatment of patients with subtypes
of MPS, a group of rare genetic disorders. Inventiva announced
positive topline data from its Phase IIa clinical trial evaluating
odiparcil for the treatment of adult MPS VI patients at the end of
2019 and received FDA Fast Track designation in MPS VI for
odiparcil in October 2020.
In parallel, Inventiva is in the process of
selecting an oncology development candidate for its Hippo
signalling pathway program. Furthermore, the Company has
established a strategic collaboration with AbbVie in the area of
autoimmune diseases. AbbVie has started the clinical development of
ABBV‑157, a drug candidate for the treatment of moderate to severe
psoriasis resulting from its collaboration with Inventiva. This
collaboration enables Inventiva to receive milestone payments upon
the achievement of pre-clinical, clinical, regulatory and
commercial milestones, in addition to royalties on any approved
products resulting from the collaboration.
The Company has a scientific team of
approximately 70 people with deep expertise in the fields of
biology, medicinal and computational chemistry, pharmacokinetics
and pharmacology, as well as in clinical development. It also 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
InventivaPascaline ClercVP of Global External
Affairs media@inventivapharma.com+1 240 620 9175 |
Brunswick GroupYannick Tetzlaff / Tristan Roquet
Montegon / Aude LepreuxMedia
relationsinventiva@brunswickgroup.com+33 1 53 96 83 83 |
Westwicke,
an ICR CompanyPatricia L. Bank Investor
relationsPatti.bank@westwicke.com+1 415 513 1284 |
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Please refer to the Universal Registration
Document for the year ended December 31, 2020 filed with the
Autorité des Marchés Financiers on March 15, 2021, the Annual
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1 For more details, please refer to:
clinicaltrial.gov/NCT04849728.
2 Site qualification is the process by which the study sponsor,
in this case Inventiva, and/or clinical research organization
determine whether the investigator and the clinical site have the
resources and capabilities necessary to conduct the study.
- Inventiva - PR - Initiation NATiV3 - EN - 08092021
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