Ipsen’s Iqirvo® receives U.S. FDA accelerated approval as a
first-in-class PPAR treatment for primary biliary cholangitis
-
Iqirvo® (elafibranor) 80
mg tablets is the first new medicine approved in nearly a decade
for the treatment of the rare liver disease called primary biliary
cholangitis
- Approval
based on positive Phase III ELATIVE trial data
- Primary
biliary cholangitis impacts approximately 100,000 people in the US
and is growing in global prevalence. If inadequately treated, it
can cause liver failure
- U.S.
approval of Iqirvo establishes Ipsen as a leader in the treatment
of rare cholestatic liver diseases
PARIS, FRANCE, 10 June 2024
Ipsen (Euronext: IPN; ADR: IPSEY) today announced that the U.S.
Food and Drug Administration (FDA) has granted accelerated approval
for Iqirvo® (elafibranor) 80 mg tablets 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. Iqirvo may be prescribed immediately in the U.S. for eligible
patients.
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). Iqirvo is not
recommended for people who have or develop decompensated cirrhosis
(e.g., ascites, variceal bleeding, hepatic encephalopathy).
“For a significant number of people living with
PBC, available treatments do not control the condition and may
exacerbate symptoms of PBC. Left unmanaged, PBC can progress,
leading to liver failure and in some cases, the need for a liver
transplant,” said Christelle Huguet, Executive Vice President, Head
of Research and Development at Ipsen. “Iqirvo demonstrated
statistically significant improvements in biochemical response
compared to UDCA alone. Iqirvo is therefore a much-needed treatment
option and the first new medicine for PBC in nearly a decade.”
Iqirvo is a first-in-class oral, once-daily
peroxisome proliferator-activated receptor (PPAR) agonist. Iqirvo
was in-licensed from GENFIT in 2021. The accelerated approval of
Iqirvo is based on data from the Phase III ELATIVE trial published
in the New England Journal of Medicine1. The ELATIVE trial
demonstrated that 13 times more patients achieved the composite
primary endpoint of biochemical response when treated with Iqirvo
plus UDCA (n=108) versus placebo plus UDCA (=53) (respectively 51%
versus 4% for a 47% treatment difference). ALP is a biochemical
marker and is used as a surrogate endpoint in PBC trials. Secondary
endpoints showed normalization in ALP levels in only Iqirvo-treated
patients (15% for Iqirvo plus UDCA (n=108) versus 0% for placebo
plus UDCA (n=53)). Most patients (95%) received study treatment
(Iqirvo or placebo) in combination with UDCA.
The most common adverse reactions with Iqirvo
reported in ≥10% of study participants were weight gain, abdominal
pain, diarrhea, nausea and vomiting. Some study participants
treated with Iqirvo experienced myalgia, myopathy and
rhabdomyolysis; fractures; adverse effects on fetal and newborn
development; drug-induced liver injury; hypersensitivity reactions;
or biliary obstruction. See full Important Safety Information
below.
“Data from the pivotal Phase III ELATIVE
clinical trial demonstrated that Iqirvo is an effective second-line
treatment for patients with PBC with favorable benefit and risk
data,” said Dr. Kris Kowdley, Director at Liver Institute
Northwest, Washington and a primary investigator on the ELATIVE
study. “The approval of Iqirvo will allow healthcare providers in
the U.S. to address an unmet need with the potential to
significantly reduce ALP levels for our patients with 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.2, the majority being women, PBC is a
lifelong condition that can worsen over time if not effectively
treated, leading to liver transplant and in some cases, premature
death. PBC also affects day-to-day life, with people most commonly
experiencing severe fatigue symptoms and debilitating itch
(pruritus).
“People living with PBC can feel like the
symptoms they experience are dismissed by family members, friends
or even their doctors, because they have not experienced something
similarly disruptive in their lives. People with PBC may also feel
uncertainty around the disease progression and if, or when, their
liver health may deteriorate,” said Carol Roberts, Executive
President of PBCers, a patient advocacy organization in the U.S.
providing support to people living with PBC. “Earlier diagnosis and
education about PBC, along with new treatment options are important
to meet the current needs of people living with PBC.”
Iqirvo has been submitted to the European
Medicines Agency (EMA) and the UK Medicines and Healthcare products
Regulatory Agency (MHRA), seeking authorization for PBC, with final
EMA and MHRA regulatory decisions anticipated in the second half of
2024. The FDA approval of Iqirvo further strengthens Ipsen’s
portfolio of treatments for rare cholestatic liver diseases
available to patients in the U.S. This includes our FDA approved
medicine for the treatment of pruritus in patients three months and
older with progressive familial intrahepatic cholestasis (PFIC) and
for the treatment of cholestatic pruritus in patients from 12
months of age with Alagille syndrome (ALGS).
IMPORTANT SAFETY
INFORMATIONMyalgia, 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 7% 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:
Suspected 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, laboratory and
imaging 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 InteractionsIQIRVO
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
PopulationsPregnancy: 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
Pharmaceuticals, 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 (800) FDA-1088 or
www.fda.gov/medwatch. You may also report side effects to
Ipsen Pharmaceuticals at 1-855-463-5127.
Please see full
Prescribing Information for IQIRVO.
About Iqirvo
Iqirvo (pronounced EYE-KER-VO) is an oral,
once-daily, peroxisome proliferator-activated receptor (PPAR)
agonist 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 has not received approval by
regulatory authorities outside of the U.S. Iqirvo is currently
under regulatory review with the European Medicines Agency (EMA)
and the UK Medicines and Healthcare products Regulatory Agency
(MHRA). Iqirvo was discovered and developed by GENFIT and Ipsen
licensed the exclusive worldwide rights (except China, Hong Kong,
Taiwan and Macau) to elafibranor from GENFIT in 2021.
Iqirvo has been granted approval under the FDA
accelerated approval program, which allows for approval of
medicines that treat serious conditions and fill an unmet medical
need based on a surrogate endpoint. Under the program, Ipsen is
required to conduct a trial to confirm anticipated clinical
benefit. The confirmatory trial for Iqirvo, ELFIDENCE, is
ongoing.
Iqirvo is an 80 mg tablet administered orally
once daily. To ensure access to Iqirvo for eligible individuals in
the U.S., the IPSEN CARES® patient support program is available as
a resource to people living with PBC and their caregivers to
provide educational support and address coverage, access and
reimbursement questions (1-866-435-5677).
About the Phase III ELATIVE
trial
ELATIVE is a multi-center, randomized
double-blind, placebo-controlled Phase III clinical trial (n=161)
that evaluated the efficacy and safety of Iqirvo 80mg once daily
plus UDCA (n=108) versus placebo plus UDCA (n=53). Iqirvo or
placebo was administered in combination with UDCA in 95% of
patients and as monotherapy in 5% of patients who were unable to
tolerate UDCA. The 52-week study was completed by 92% of
participants with 97% of those who completed the study continuing
in an extension study. The results were published in the New
England Journal of Medicine1.
- The ELATIVE trial demonstrated that
Iqirvo had a statistically significant treatment benefit with 51%
of patients on Iqirvo achieving a biochemical response compared
with 4% on the placebo arm, a treatment benefit of 47% (95% CI 32,
57; p<0.0001). Biochemical response was defined as ALP less than
1.67 Upper Limit of Normal (ULN), an ALP decrease of greater than
or equal to 15% from baseline and total bilirubin (TB) ≤ ULN at
week 52.
- ALP normalization at week 52 was a
key secondary endpoint with 15% of Iqirvo-treated patients
demonstrating normalization versus 0% placebo (p=0.002).
- The significant biochemical
response to Iqirvo was further supported by data demonstrating
reductions from baseline in ALP levels were sustained through week
52 and response was rapid, seen as early as Week 4 in the Iqirvo
group.
- The most common adverse reactions
with Iqirvo reported in ≥10% of study participants were weight
gain, abdominal pain, diarrhea, nausea and vomiting.
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
- Craig
Marks | + 44 (0)7584 34 91 93
- Nicolas
Bogler | + 33 6 52 19 98 92
Media
- Amy Wolf
| + 41 79 576 07 23 | amy.wolf@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
IpsenThe 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
- Kowdley. K.V, et al. Efficacy and
Safety of Elafibranor in Primary Biliary Cholangitis. NEJM. 2023.
DOI: 10.1056/NEJMoa2306185
- Lu 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 FDA approval _10062024
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