Iqirvo® (elafibranor) data shows efficacy and safety for up to 3
years in patients with PBC with improvements in fatigue and
pruritus
- Ipsen
presents 3 late-breaking presentations and 8 abstracts across rare
cholestatic liver disease portfolio at AASLD
2024
- Iqirvo
approved for use in the U.S. in June 2024, in the E.U. in September
2024 and in the U.K. in October 2024
PARIS, FRANCE, 15 November 2024
Ipsen (Euronext: IPN; ADR: IPSEY) announced today late-breaking
data for Iqirvo® (elafibranor 80 mg tablets) from an
interim analysis of the ongoing open-label extension of the Phase
III ELATIVE® study at the American Association for the
Study of Liver Disease (AASLD) congress. The late-breaking
presentations (Abstract #5041 and Abstract #5042) report on
biomarkers of cholestasis, stabilization of surrogate markers of
liver fibrosis and moderate-to-severe pruritus data for up to three
years in Iqirvo-treated patients. Additionally, exploratory
endpoints in fatigue and sleep were evaluated using
patient-reported outcomes tools.
“Over three years, Iqirvo data suggest sustained
efficacy and support the safety profile of the medicine.
Importantly, when patients tell me they are less impacted by itch
and fatigue—that matters to me as a physician,” said Dr. Kris
Kowdley, Director at The Liver Institute Northwest, Washington and
a primary investigator on the ELATIVE study. “Treatment with Iqirvo
had an impact on symptoms of pruritus and surrogate markers of
fibrosis, which are important findings for people living with
PBC.”
“Fatigue is a symptom often reported by people
living with PBC and is also very challenging to manage,” said Dr.
Mark Swain, Department of Medicine, Cumming School of Medicine,
University of Calgary, Canada. “Patients treated with Iqirvo
reported improvement in fatigue and sleep, across several
patient-reported outcome measures.”
The open-label extension (OLE) included 138
patients who completed the double-blind period of the Phase III
ELATIVE® study1. This interim analysis was
performed after at least one year of treatment with Iqirvo in the
OLE (up to three years total). In patients receiving three years of
continuous treatment with Iqirvo across the double-blind period and
OLE (n=13), 85 percent had a biochemical response (n=11/13; ALP
<1.67 x ULN, with ≥ 15% reduction from baseline and total
bilirubin ≤ ULN) and 39 percent achieved ALP normalization (n=5/13)
at week 156. Surrogate markers of liver fibrosis, liver stiffness
measurements (n=23) and enhanced liver fibrosis (ELF™) (n=19)
scores, suggest stabilization when measured from baseline to week
130. In patients continuously receiving Iqirvo for up to 156 weeks,
pruritus improvements were sustained for patients with moderate or
severe pruritus at baseline (n=5).
No new safety findings were observed. The most
common treatment-emergent adverse events (>10 percent) occurring
more frequently in patients treated with Iqirvo than placebo in the
double-blind period of the trial (abdominal pain, diarrhea, nausea
and vomiting) were also reported in the OLE.
The impact of Iqirvo on fatigue and sleep were
investigated as an exploratory endpoint in the OLE.2
Changes in fatigue or sleepiness (including normal sleep) were
reviewed from baseline to week 104 looking at the minimal
clinically important differences and categorical changes (n=48).
Fatigue and sleep improvements for patients treated with Iqirvo
were observed at week 104 across three patient-reported outcome
(PRO) tools. In patients with moderate-to-severe fatigue or
excessive sleepiness at baseline, clinically meaningful
improvements were observed after 104 weeks of treatment with Iqirvo
in 56 percent (n=18) of patients according to the PRO Measurement
Information System (PROMIS) Fatigue Short Form 7a, 50 percent
(n=24) of patients according to the fatigue domain of the PBC-40,
and 69 percent (n=16) of patients according to the Epworth
Sleepiness Scale (ESS). These are interim data and have not been
submitted to regulatory agencies. A confirmatory study of Iqirvo is
ongoing (NCT06016842).
“People living with PBC tell us just how
devastating this disease can be for patients and their families,”
said Sandra Silvestri, EVP and Chief Medical Officer, Ipsen. “Data
like these continue to provide prescribers with a clear rationale
for Iqirvo. As the first-in-class PPAR approved for the treatment
of PBC, Iqirvo is on track to be the treatment of choice for
patients living with PBC. Ipsen is committed to being a leader the
rare liver community can count on.”
About PBC
PBC is a rare, autoimmune, cholestatic liver disease where a
build-up of bile and toxins (cholestasis) and chronic inflammation
causes irreversible fibrosis (scarring) of the liver and
destruction of the bile ducts. Impacting approximately 100,000
people in the U.S.,3 the majority being women, PBC is a
lifelong condition that can worsen over time if not effectively
treated, may lead to liver transplant and in some cases, premature
death. The high symptom burden of PBC can also have an impact on
daily life.
Iqirvo (elafibranor) posters presented at
AASLD
Poster or Oral # |
Full Title |
Authors |
Poster, Abstract [5041]
Monday 18 November
13:00–14:00
Poster Session IV |
Long-term efficacy and safety of elafibranor in primary biliary
cholangitis:
Interim results from the open-label extension of the
ELATIVE® trial up to 3 years |
Kris V. Kowdley et al. |
Poster, Abstract [5042]
Monday 18 November
13:00–14:00
Poster Session IV |
Impact of elafibranor on fatigue in patients with primary biliary
cholangitis:
Interim results from the long-term open-label extension of the
ELATIVE® trial |
Mark Swain et al. |
Poster, Abstract [4274]
Monday 18 November
13:00–14:00
Poster Session IV |
Beyond the mean: Exploring the impact of baseline alkaline
phosphatase levels on endpoints in primary biliary
cholangitis |
Cynthia Levy et al. |
Oral, Abstract Parallel, ePoster [43]
Monday 18 November
11:00–11:15
Human Cholestatic, PBC and other Biliary Disorders in Children and
Adults |
One-year treatment with elafibranor in the Phase III
ELATIVE® trial improves GLOBE and UK-PBC prognostic
scores |
Kris V. Kowdley et al. |
Poster, Abstract [4292]
Monday 18 November
13:00–14:00
Poster Session IV |
Use of machine learning (ML) models to stratify response patterns
to first-line treatment of primary biliary cholangitis (PBC) with
ursodeoxycholic acid (UDCA) |
Seema T. Meloni et al. |
Poster, Abstract [4349]
Monday 18 November
13:00–14:00
Poster Session IV |
Elafibranor has no impact on markers of renal function in primary
biliary cholangitis: results from the Phase III ELATIVE®
trial |
Marcelo Kugelmas et al. |
Poster, Abstract [4358]
Monday 18 November
13:00–14:00
Poster Session IV |
Economic burden of patients with primary biliary cholangitis and
experiencing fatigue or pruritus in the United States |
Nisreen Shamseddine et al. |
About Iqirvo®
(elafibranor) 80 mg tablet
Iqirvo is an oral, once-daily, peroxisome proliferator-activated
receptor (PPAR), indicated for the treatment of primary biliary
cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA)
in adults who have an inadequate response to UDCA, or as
monotherapy in patients unable to tolerate UDCA. While the
mechanism is not well understood, pharmacological activity that is
potentially relevant to Iqirvo therapeutic effects includes
inhibition of bile acid synthesis through activation of PPAR-alpha
and PPAR-delta. In 2019, Iqirvo was granted Breakthrough Therapy
Designation by the U.S Food and Drug Administration (FDA) in adults
with PBC who have an inadequate response to ursodeoxycholic acid
(UDCA) the existing first-line therapy for PBC. Iqirvo was granted
U.S. FDA accelerated approval in June 2024, EU conditional approval
by the EMA in September 2024 and UK Medicines and Healthcare
products Regulatory Agency (MHRA) approval in October 2024, for the
treatment of primary biliary cholangitis (PBC) in combination with
ursodeoxycholic acid (UDCA) in adults who have an inadequate
response to UDCA, or as monotherapy in patients unable to tolerate
UDCA. The FDA and EMA approvals are contingent on the further
verification of clinical benefit. Iqirvo is currently in regulatory
processes with other authorities. Iqirvo (elafibranor) was
developed by GENFIT. Ipsen licensed the exclusive worldwide rights
(except China, Hong Kong, Taiwan and Macau) to elafibranor from
GENFIT in 2021.
INDICATION
IQIRVO® is indicated for the treatment of primary biliary
cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA)
in adults with an inadequate response to UDCA, or as monotherapy in
adults unable to tolerate UDCA.
This indication is approved under accelerated
approval based on reduction of alkaline phosphatase (ALP).
Improvement in survival or prevention of liver decompensation
events have not been demonstrated. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in confirmatory trial(s).
Limitations of Use
Use of IQIRVO is not recommended in patients who have or develop
decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic
encephalopathy).
IMPORTANT SAFETY
INFORMATION
Myalgia, Myopathy, and
Rhabdomyolysis: Rhabdomyolysis resulting in acute
kidney injury occurred in one IQIRVO-treated patient who had
cirrhosis at baseline and was also taking a stable dose of an
HMG-CoA reductase inhibitor (statin). Myalgia or myopathy, with or
without CPK elevations, occurred in patients treated with IQIRVO
alone or treated concomitantly with a stable dose of an HMG-CoA
reductase inhibitor. Assess for myalgia and myopathy prior to
IQIRVO initiation. Consider periodic assessment (clinical exam, CPK
measurement) during treatment with IQIRVO, especially in those who
have signs and symptoms of new onset or worsening of muscle pain or
myopathy. Interrupt IQIRVO treatment if there is new onset or
worsening of muscle pain, or myopathy, or rhabdomyolysis.
Fractures: Fractures
occurred in 6% of IQIRVO-treated patients compared to no
placebo-treated patients. Consider the risk of fracture in the care
of patients treated with IQIRVO and monitor bone health according
to current standards of care.
Adverse Effects on Fetal and Newborn
Development: IQIRVO may cause fetal harm when
administered during pregnancy. For females of reproductive
potential, verify that the patient is not pregnant prior to
initiation of therapy. Advise females of reproductive potential to
use effective non-hormonal contraceptives or add a barrier method
when using systemic hormonal contraceptives during treatment with
IQIRVO and for 3 weeks following the last dose of IQIRVO.
Drug-Induced Liver
Injury: Drug-induced liver injury occurred in one
patient who took IQIRVO 80 mg once daily and two patients who took
IQIRVO at 1.5-times the recommended dosage, of which one presented
with autoimmune-like hepatitis. The median time to onset of
elevation in liver tests was 85 days. Obtain baseline clinical and
laboratory assessments at treatment initiation with IQIRVO and
monitor thereafter according to routine patient management.
Interrupt IQIRVO treatment if liver tests (ALT, AST, total
bilirubin [TB], and/or alkaline phosphatase [ALP]) worsen, or the
patient develops signs and symptoms consistent with clinical
hepatitis (e.g., jaundice, right upper quadrant pain,
eosinophilia). Consider permanent discontinuation if liver tests
worsen after restarting IQIRVO.
Hypersensitivity
Reactions: Hypersensitivity reactions have occurred
in a clinical trial with IQIRVO at 1.5-times the recommended
dosage. Three patients (0.2%) had rash or unspecified allergic
reaction that occurred 2 to 30 days after IQIRVO initiation.
Hypersensitivity reactions resolved after discontinuation of IQIRVO
and treatment with steroids and/or antihistamines. If a severe
hypersensitivity reaction occurs, permanently discontinue IQIRVO.
If a mild or moderate hypersensitivity reaction occurs, interrupt
IQIRVO and treat promptly. Monitor the patient until signs and
symptoms resolve. If a hypersensitivity reaction recurs after
IQIRVO rechallenge, then permanently discontinue IQIRVO.
Biliary Obstruction: Avoid
use of IQIRVO in patients with complete biliary obstruction. If
biliary obstruction is suspected, interrupt IQIRVO and treat as
clinically indicated.
Drug-Drug Interactions
IQIRVO may reduce the systemic exposure of
progestin and ethinyl estradiol (CYP3A4 substrates), which may lead
to contraceptive failure and/or an increase in breakthrough
bleeding. Switch to effective non-hormonal contraceptives or add a
barrier method when using hormonal contraceptives during treatment
with IQIRVO and for at least 3 weeks after last dose.
CPK elevation and/or myalgia occurred in
patients on IQIRVO monotherapy. Co-administration of IQIRVO and
HMG-CoA reductase inhibitors can increase the risk of myopathy.
Monitor for signs and symptoms of muscle injury. Consider periodic
assessment (clinical exam, CPK) during treatment. Interrupt IQIRVO
treatment if there is new onset or worsening of muscle pain or
myopathy.
Co-administration of IQIRVO with rifampin, an
inducer of metabolizing enzymes, may reduce the systemic exposure
of elafibranor resulting in delayed or suboptimal biochemical
response. Monitor the biochemical response (e.g., ALP and
bilirubin) when patients initiate rifampin during treatment with
IQIRVO.
Bile acid sequestrants may interfere with IQIRVO
absorption and systemic exposure, which may reduce efficacy.
Administer IQIRVO at least 4 hours before or after a bile acid
sequestrant, or at as great an interval as possible.
Use in Special Populations
Pregnancy: Based on data
from animal reproduction studies, IQIRVO may cause fetal harm when
administered during pregnancy. There are insufficient data from
human pregnancies exposed to IQIRVO to allow an assessment of a
drug-associated risk of major birth defects, miscarriage, or other
adverse maternal or fetal outcomes. Report pregnancies to Ipsen
Biopharmaceuticals, Inc. adverse event reporting line at
1-855-463-5127 or https://www.ipsen.com/contact-us/.
Lactation: There are no data available on the
presence of IQIRVO or its metabolites in human milk, or on effects
of the drug on the breastfed infant or the effects on milk
production. IQIRVO is not recommended during breastfeeding and for
at least 3 weeks following last dose of IQIRVO because the risk to
breastfed child cannot be excluded.
Females and Males of Reproductive
Potential: IQIRVO may cause fetal harm when
administered to pregnant women. Verify the pregnancy status of
females of reproductive potential prior to initiating IQIRVO.
Advise females of reproductive potential to use effective
contraception during treatment with IQIRVO and for 3 weeks after
the final dose.
The most common adverse events occurring in ≥10%
of patients were weight gain (23%), abdominal pain (11%), nausea
(11%), vomiting (11%), and diarrhea (11%).
You are encouraged to report side
effects to FDA at 1-800-FDA-1088
or www.fda.gov/medwatch. You
may also report side effects to Ipsen Biopharmaceuticals, Inc. at
1-855-463-5127.
Please see
full Prescribing
Information for IQIRVO in
the U.S.
Please see full Prescribing
Information for IQIRVO in the
E.U.
ENDS
About Ipsen
We are a global biopharmaceutical company with a focus on bringing
transformative medicines to patients in three therapeutic areas:
Oncology, Rare Disease and Neuroscience.
Our pipeline is fueled by external innovation
and supported by nearly 100 years of development experience and
global hubs in the U.S., France and the U.K. Our teams in more than
40 countries and our partnerships around the world enable us to
bring medicines to patients in more than 80 countries.
Ipsen 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.
Ipsen contacts
Investors
- Nicolas
Bogler | + 33 6 52 19 98 92
Media
- Jennifer
Smith-Parker | + 44 7843 13 77 64 |
jennifer.smith-parker.ext@ipsen.com
- Rachel
Reiff | + 1 908 616 1680 | rachel.reiff@ipsen.com
- Anna
Gibbins | + 44 7717 80 19 00| anna.gibbins@ipsen.com
Disclaimers and/or 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.
References
1.Kowdley. K,. et al. Long term efficacy
and safety of elafibranor in primary biliary cholangitis: Interim
results from the open-label extension of the ELATIVE®
trial up to 3 years . Poster, Abstract 5041. American Association
for the Study of Liver Disease (AASLD).2024
2.Swain. M, et al. Impact of elafibranor on fatigue in
patients with primary biliary cholangitis: Interim results from the
long-term open-label extension of the ELATIVE® trial .
Poster, Abstract 5042. American Association for the Study of Liver
Disease (AASLD).2024
3Lu M, Zhou, et al. Fibrotic Liver Disease Consortium
Investigators. Increasing Prevalence of Primary Biliary Cholangitis
and Reduced Mortality With Treatment. Clin Gastroenterol Hepatol.
2018 Aug;16(8):1342-1350.e1. DOI: 10.1016/j.cgh.2017.12.033.
- Ipsen PR_Iqirvo® (elafibranor) data shows efficacy and safety
for up to 3 years_15112024
Ipsen (EU:IPN)
Gráfico Histórico do Ativo
De Nov 2024 até Dez 2024
Ipsen (EU:IPN)
Gráfico Histórico do Ativo
De Dez 2023 até Dez 2024