GENFIT: Results from Ipsen’s ELATIVE® pivotal Phase III trial of
elafibranor in PBC presented as late breaking data at AASLD
congress and published in New England Journal of Medicine
- ELATIVE® Phase III trial
confirms potential for investigational elafibranor as a novel,
first-in-class, dual PPAR α,δ agonist for patients with Primary
Biliary Cholangitis.
- Elafibranor demonstrates
significant improvements in biomarkers of disease progression
versus placebo, including significant treatment benefit with
improvement in biochemical response and alkaline phosphatase (ALP)
normalization, along with patient-reported outcomes data suggesting
a possible improvement in pruritus.
- Elafibranor was generally
well-tolerated with a well-documented safety profile consistent
with previous trials.
Paris (France), November 13,
2023 – Ipsen (Euronext: IPN; ADR: IPSEY) and
GENFIT (Nasdaq and Euronext: GNFT) today announced full
results from the pivotal Phase III ELATIVE® trial, which are being
presented in a late-breaking oral session (Abstract #484, Monday,
13 November at 16.45 EST) at the American Association for the Study
of Liver Diseases (AASLD) and simultaneously published in New
England Journal of Medicine (NEJM). This trial evaluated the
efficacy and safety of investigational elafibranor, an oral, dual
PPAR α,δ agonist, as a potential novel class of treatment for
patients with the rare, autoimmune cholestatic liver disease,
Primary Biliary Cholangitis (PBC).
Results show statistically significant
improvements in biomarkers of disease progression across key
endpoints with a significant treatment benefit achieved in the
primary composite endpoint, demonstrating a 47% placebo-adjusted
difference (P<0.001) between patients on elafibranor 80mg (51%)
compared with patients on placebo (4%) achieving a biochemical
response. In the trial, a biochemical response is defined as
alkaline phosphatase (ALP) <1.67 x upper limit of normal (ULN),
an ALP decrease ≥ 15 percent and total bilirubin (TB) ≤ ULN at 52
weeks. ALP and bilirubin are important predictors of PBC disease
progression. Reductions in levels of both can indicate reduced
cholestatic injury and improved liver function.
Only patients receiving elafibranor achieved
normalization of ALP (upper limit of normal 104 U/L in females and
129 U/L in males) at Week 52 (15% vs 0% placebo, P=0.002), a key
secondary endpoint of the trial. The significant biochemical effect
of elafibranor measured by ALP reduction was further supported by
data demonstrating reductions from baseline in ALP levels were
rapid, seen as early as Week 4 in the elafibranor group, and were
sustained through Week 52, with a decrease in ALP of 41% on
elafibranor compared with placebo.
“When managing PBC, our first goal is to
effectively control the disease progression which can lead to liver
failure. The results from ELATIVE® provide compelling evidence that
elafibranor has the potential to achieve this goal, with evidence
of a highly significant treatment benefit that is associated with
improved clinical outcomes,” said Dr Christopher Bowlus,
Professor of Gastroenterology and Hepatology, University of
California Davis, U.S. “In addition, our patients need
relief from the significant symptom burden of PBC, particularly
those with moderate to severe itch. Data from ELATIVE® demonstrated
the possibility of improved pruritus for patients taking
elafibranor compared with those on placebo. Taken together, these
data suggest elafibranor could offer an effective new treatment
opportunity for PBC management.”
ELATIVE® investigated the effect of treatment
with elafibranor on pruritus (severe itch) across three separate
patient-reported outcome measures. On the key secondary endpoint
using the PBC Worst Itch NRS score, the reduction of pruritus
observed for elafibranor versus placebo was not statistically
significant (LS mean, –1.93 versus –1.15; difference, –0.78; 95%
CI, –1.99 to 0.42; P=0.20). Two other secondary patient-reported
outcome measures were used to assess itch, and greater reductions
in pruritus were observed with elafibranor compared with placebo at
Week 52, according to the itch domain of PBC-40 quality of life
questionnaire (LS mean difference -2.3; 95% CI, -4.0 to -0.7) and
5-D Itch total score (LS mean difference, -3.0; 95% CI, -5.5 to
-0.5).
“We believe these data suggest that elafibranor
could be a paradigm-changing treatment meeting the unmet need for
an effective second-line option,” said Christelle Huguet,
EVP and Head of Research and Development, Ipsen. “These
data from ELATIVE® have provided a better understanding of how we
can effectively manage both disease progression and the symptom
burden still experienced by many people living with PBC. It would
not have been possible for us to investigate the potential for new
innovative treatments without the involvement of the patients and
their wider families and caregivers, to whom we are immensely
grateful. We are also enormously grateful to the study
investigators, who have supported us and provided us with the
benefit of their expertise in designing and running this
study.”
PBC is a rare, autoimmune, cholestatic liver disease, affecting
approximately nine women for every one man. A build-up of bile and
toxins (cholestasis) and chronic inflammation causes irreversible
fibrosis (scarring) of the liver and destruction of the bile ducts.
It is a life-long condition that can worsen over time if not
effectively treated, leading to liver transplant and in some cases,
premature death. PBC impacts patients’ daily lives through
debilitating symptoms including, most commonly, pruritus and
fatigue. Currently, there are no approved treatments available that
can effectively manage both disease progression and life-impacting
symptoms.
“Living with PBC can be very challenging for
many people. The fear of the disease progressing hangs over you,
and you have to manage as best you can with the daily symptom
burden, symptoms that can sometimes be so debilitating it takes
every ounce of strength to get through another day,” explained
Mo Christie, Head of Patient Services, PBC Foundation,
UK. “As someone who is living with PBC, I appreciate the
need for clinicians, other patients, and families to understand the
condition and the impact that coming to terms with living with an
incurable condition can have on a person’s life. The impact can be
enormous, so it is vitally important to all aspects of our lives
that we can access knowledge, care and effective medicines, when we
see our clinicians.”
Elafibranor was well tolerated in the trial.
Similar percentages of patients in the treatment group and the
placebo group experienced adverse events, treatment-related adverse
events, severe or serious adverse events or adverse events leading
to discontinuation. Adverse events occurring in >10% of patients
and more frequently on elafibranor versus placebo included
abdominal pain, diarrhea, nausea, and vomiting. Elafibranor has a
well-documented safety profile across a broad patient population
and is consistent with cumulative safety data from past elafibranor
trials in other indications, including NASH.
Data from ELATIVE® are being used to support
submissions for elafibranor as a treatment for PBC with regulatory
authorities worldwide.
ENDS
ABOUT
ELATIVE®
ELATIVE® is a multi-center, randomized,
double-blind, placebo-controlled Phase III clinical trial, with an
open-label long-term extension (NCT03124108). ELATIVE® is
evaluating the efficacy and safety of elafibranor 80mg once daily
versus placebo for the treatment of patients with PBC with an
inadequate response or intolerance to ursodeoxycholic acid (UDCA),
the existing first-line therapy for PBC. The trial enrolled 161
patients who were randomized 2:1 to receive elafibranor 80mg once
daily or placebo. Patients with an inadequate response to UDCA
would continue to receive UDCA in combination with elafibranor or
placebo, while patients unable to tolerate UDCA would receive only
elafibranor or placebo.
ABOUT ELAFIBRANOR
Elafibranor is a novel, oral, once-daily, dual
peroxisome activated receptor (PPAR) alpha/delta (α,δ) agonist,
currently under investigation as a treatment for patients with PBC,
a rare liver disease. Concurrent α,δ activation targets
inflammation, cholestasis and fibrosis in PBC. In 2019, elafibranor
was granted a Breakthrough Therapy Designation by the FDA in adults
with PBC who have an inadequate response to UDCA. Elafibranor has
not received approval by regulatory authorities anywhere in the
world.
ABOUT GENFIT
GENFIT is a late-stage biopharmaceutical company
dedicated to improving the lives of patients with rare and
life-threatening liver diseases characterized by high unmet medical
needs. GENFIT is a pioneer in liver disease research and
development with a rich history and strong scientific heritage
spanning more than two decades. Today, GENFIT has a growing and
diversified pipeline with programs at various development stages.
The Company’s area of focus is Acute on Chronic Liver Failure
(ACLF). Its ACLF franchise consists of five assets in development:
VS-01, NTZ, SRT-015, CLM-022 and VS-02-HE. These are all based on
differentiated mechanisms of action leveraging complementary
pathways. Other assets target other life-threatening disease
indications such as cholangiocarcinoma (CCA) and Urea Cycle
Disorders (UCD)/Organic Acidemias (OA). GENFIT’s track record in
bringing early-stage assets with high potential to late development
and pre-commercialization stages is highlighted in the successful
52-week Phase 3 ELATIVE® trial evaluating elafibranor in PBC.
Beyond therapeutics, GENFIT’s pipeline also includes a diagnostic
franchise focused on Metabolic dysfunction-associated
steatohepatitis (MASH) previously known as nonalcoholic
steatohepatitis (NASH) and ammonia. GENFIT has facilities in Lille
and Paris (France), Zurich (Switzerland) and Cambridge, MA (USA).
GENFIT is a publicly traded company listed on the Nasdaq Global
Select Market and on compartment B of Euronext’s regulated market
in Paris (Nasdaq and Euronext: GNFT). In 2021, IPSEN became one of
GENFIT’s largest shareholders and holds 8% of the company’s share
capital. For more information, visit www.genfit.com
ABOUT IPSEN
Ipsen is a global, mid-sized biopharmaceutical
company focused on transformative medicines in Oncology, Rare
Disease and Neuroscience. With total sales of €3.0bn in FY 2022,
Ipsen sells medicines in over 100 countries. Alongside its
external-innovation strategy, the Company’s research and
development efforts are focused on its innovative and
differentiated technological platforms located in the heart of
leading biotechnological and life-science hubs: Paris-Saclay,
France; Oxford, U.K.; Cambridge, U.S.; Shanghai, China. Ipsen has
around 5,300 colleagues worldwide and is listed in Paris (Euronext:
IPN) and in the U.S. through a Sponsored Level I American
Depositary Receipt program (ADR: IPSEY). For more information,
visit ipsen.com
GENFIT – FORWARD LOOKING
STATEMENTS
This press release contains certain
forward-looking statements, including those within the meaning of
the Private Securities Litigation Reform Act of 1995 with respect
to GENFIT, including, but not limited to statements about the
potential of elafibranor as a safe and effective second-line
treatment for PBC, the opportunity to manage the disease
progression and the potential of elafibranor to improve pruritus,
reduce cholestatic injury and improve liver function. The use of
certain words, including “believe”, “potential,” “expect”,
“target”, “may” and “will” and similar expressions, is intended to
identify forward-looking statements. Although the Company believes
its expectations are based on the current expectations and
reasonable assumptions of the Company’s management, these
forward-looking statements are subject to numerous known and
unknown risks and uncertainties, which could cause actual results
to differ materially from those expressed in, or implied or
projected by, the forward-looking statements. These risks and
uncertainties include, among other things, the uncertainties
inherent in research and development, including in relation to
safety of drug candidates, cost of, progression of, and results
from, our ongoing and planned clinical trials, review and approvals
by regulatory authorities in the United States, Europe and
worldwide, of our drug and diagnostic candidates, potential
commercial success of elafibranor if approved, exchange rate
fluctuations, our continued ability to raise capital to fund our
development, as well as those risks and uncertainties discussed or
identified in the Company’s public filings with the AMF, including
those listed in Chapter 2 “Main Risks and Uncertainties” of the
Company’s 2022 Universal Registration Document filed with the AMF
on April 18, 2023, which is available on the Company’s website
(www.genfit.com) and on the website of the AMF (www.amf-france.org)
and public filings and reports filed with the U.S. Securities and
Exchange Commission (“SEC”) including the Company’s 2022 Annual
Report on Form 20-F filed with the SEC on April 18, 2023 and
subsequent filings and reports filed with the AMF or SEC, including
the Half-Year Business and Financial Report at June 30, 2023 or
otherwise made public, by the Company. In addition, even if the
Company’s results, performance, financial condition and liquidity,
and the development of the industry in which it operates are
consistent with such forward-looking statements, they may not be
predictive of results or developments in future periods. These
forward-looking statements speak only as of the date of publication
of this document. Other than as required by applicable law, the
Company does not undertake any obligation to update or revise any
forward-looking information or statements, whether as a result of
new information, future events or otherwise.
IPSEN – FORWARD LOOKING
STATEMENTS
The forward-looking statements, objectives and
targets contained herein are based on Ipsen’s management strategy,
current views and assumptions. Such statements involve known and
unknown risks and uncertainties that may cause actual results,
performance or events to differ materially from those anticipated
herein. All of the above risks could affect Ipsen’s future ability
to achieve its financial targets, which were set assuming
reasonable macroeconomic conditions based on the information
available today. Use of the words ‘believes’, ‘anticipates’ and
‘expects’ and similar expressions are intended to identify
forward-looking statements, including Ipsen’s expectations
regarding future events, including regulatory filings and
determinations. Moreover, the targets described in this document
were prepared without taking into account external-growth
assumptions and potential future acquisitions, which may alter
these parameters. These objectives are based on data and
assumptions regarded as reasonable by Ipsen. These targets depend
on conditions or facts likely to happen in the future, and not
exclusively on historical data. Actual results may depart
significantly from these targets given the occurrence of certain
risks and uncertainties, notably the fact that a promising medicine
in early development phase or clinical trial may end up never being
launched on the market or reaching its commercial targets, notably
for regulatory or competition reasons. Ipsen must face or might
face competition from generic medicine that might translate into a
loss of market share. Furthermore, the research and development
process involves several stages each of which involves the
substantial risk that Ipsen may fail to achieve its objectives and
be forced to abandon its efforts with regards to a medicine in
which it has invested significant sums. Therefore, Ipsen cannot be
certain that favorable results obtained during preclinical trials
will be confirmed subsequently during clinical trials, or that the
results of clinical trials will be sufficient to demonstrate the
safe and effective nature of the medicine concerned. There can be
no guarantees a medicine will receive the necessary regulatory
approvals or that the medicine will prove to be commercially
successful. If underlying assumptions prove inaccurate or risks or
uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements. Other risks
and uncertainties include but are not limited to, general industry
conditions and competition; general economic factors, including
interest rate and currency exchange rate fluctuations; the impact
of pharmaceutical industry regulation and healthcare legislation;
global trends toward healthcare cost containment; technological
advances, new medicine and patents attained by competitors;
challenges inherent in new-medicine development, including
obtaining regulatory approval; Ipsen's ability to accurately
predict future market conditions; manufacturing difficulties or
delays; financial instability of international economies and
sovereign risk; dependence on the effectiveness of Ipsen’s patents
and other protections for innovative medicines; and the exposure to
litigation, including patent litigation, and/or regulatory actions.
Ipsen also depends on third parties to develop and market some of
its medicines which could potentially generate substantial
royalties; these partners could behave in such ways which could
cause damage to Ipsen’s activities and financial results. Ipsen
cannot be certain that its partners will fulfil their obligations.
It might be unable to obtain any benefit from those agreements. A
default by any of Ipsen’s partners could generate lower revenues
than expected. Such situations could have a negative impact on
Ipsen’s business, financial position or performance. Ipsen
expressly disclaims any obligation or undertaking to update or
revise any forward-looking statements, targets or estimates
contained in this press release to reflect any change in events,
conditions, assumptions or circumstances on which any such
statements are based, unless so required by applicable law. Ipsen’s
business is subject to the risk factors outlined in its
registration documents filed with the French Autorité des Marchés
Financiers. The risks and uncertainties set out are not exhaustive
and the reader is advised to refer to Ipsen’s latest Universal
Registration Document, available on ipsen.com.
GENFIT CONTACTS
INVESTORS
Jean-Christophe Marcoux – Chief Corporate
Affairs Officer | Tel: +33 3 2016 4000 |
jean-christophe.marcoux@genfit.com
MEDIA
Stephanie Boyer – Press relations | Tel: +333
2016 4000 | stephanie.boyer@genfit.com
IPSEN CONTACTS
INVESTORS
Craig Marks – Vice President, Investor Relations
| Tel: +44 (0)7584 349 193
Nicolas Bogler – Investor Relations Manager |
Tel: +33 6 52 19 98 92
MEDIA
Anna Gibbins – Global Head of Franchise
Communications, Rare Disease | Tel: +44 (0)7717801900
Ioana Piscociu – Senior Manager Global Media
Relations | Tel: +33 6 69 09 12 96
Amy Wolf – VP, Head of Corporate Brand Strategy
& Communications | Tel: +41 79 576 07 23
GENFIT | 885 Avenue Eugène Avinée, 59120 Loos -
FRANCE | +333 2016 4000 | www.genfit.com
- GENFIT: Results from Ipsen’s ELATIVE® pivotal Phase III trial
of elafibranor in PBC presented as late breaking data at AASLD
congress and published in New England Journal of Medicine
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