- The positive CHMP opinion for upadacitinib is based on
results from two induction studies and one maintenance
study1-4
- Crohn's disease is a chronic, systemic disease that
manifests as inflammation within the gastrointestinal tract,
causing persistent diarrhea and abdominal
pain5,6
- If approved by the European Commission (EC), this will be
the seventh indication for upadacitinib in the European Union (EU),
and the first JAK inhibitor for Crohn's disease, adding to AbbVie's
gastroenterology portfolio
NORTH
CHICAGO, Ill., Feb. 27,
2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced the European Medicines Agency's (EMA) Committee for
Medicinal Products for Human Use (CHMP) recommended the approval of
upadacitinib (RINVOQ®, 45 mg [induction dose] and 15 mg
and 30 mg [maintenance doses]) for the treatment of adult patients
with moderately to severely active Crohn's disease who have had an
inadequate response, lost response or were intolerant to either
conventional therapy or a biologic agent.1-4
"The recent CHMP recommendation to approve upadacitinib for use
in Crohn's disease is a momentous step, bringing us closer to
offering a first-of-its-kind, once-daily oral treatment that can
make a difference for people living with this disease,"
said Roopal Thakkar, M.D., senior vice president, development,
regulatory affairs and chief medical officer, AbbVie. "We remain
steadfast in our commitment to researching and developing treatment
options as part of a diverse portfolio of therapies for those
living with inflammatory bowel diseases."
AbbVie's application for the approval of upadacitinib in Crohn's
disease is supported by data from two induction studies, U-EXCEED
and U-EXCEL, and one maintenance study, U-ENDURE.1
Patients receiving upadacitinib were treated with 45 mg once daily
for the induction studies, and were randomized to receive either 15
mg or 30 mg once-daily doses for the maintenance
study.1-4 Across all three Phase 3 studies, a
significantly greater proportion of patients treated with
upadacitinib achieved the co-primary endpoints of clinical
remission per SF/AP (defined as average daily stool frequency [SF]
≤2.8 and abdominal pain [AP] score ≤1.0 and neither greater than
baseline) and endoscopic response (defined as decrease in simple
endoscopic score for Crohn's disease [SES-CD] >50% from
baseline of the induction) compared to placebo.1-4
In all three studies, a statistically significant greater
proportion of patients treated with upadacitinib achieved the key
secondary endpoint of endoscopic remission (defined as SES-CD
≤4 and at least a 2-point reduction vs. baseline and no subscore
>1). Additionally, more upadacitinib-treated patients achieved
SES-CD ulcerated surface subscore of 0 at weeks 12 and
52 (nominal p-value<0.001) in patients with SES-CD
ulcerated surface subscore ≥1 at baseline.1-4,* Absence
or disappearance of ulceration coupled with improvements seen by
endoscopy are associated with mucosal healing.7-10
The safety profile of upadacitinib in Crohn's disease was
generally consistent with the known safety profile of
upadacitinib.1-4 Similar rates of serious adverse events
including serious infections were observed between patients
receiving upadacitinib and placebo. Reports of malignancy, major
cardiovascular events, venous thromboembolic events and
gastrointestinal perforation were infrequently observed (<1.0
Events/100 Patient-Years).
"The impact of Crohn's disease extends beyond the gut to include
systemic symptoms such as fatigue, bowel symptoms and social and
emotional functioning. Treatment options that achieve critical
endpoints such as clinical remission and endoscopic response can
make a difference in managing the challenging symptoms of this
condition and health-related outcomes related to quality of life,"
said Jean-Frédéric Colombel, M.D., professor of medicine
and director of Inflammatory Bowel Disease Center, Icahn School of
Medicine, Mount Sinai and study investigator. "Upadacitinib
could be a promising treatment option for patients who live with
uncontrolled moderate to severe Crohn's disease. I look forward to
the European Commission's final decision."
RINVOQ is approved in the EU for the treatment of adults with
radiographic axial spondylarthritis, non-radiographic axial
spondylarthritis, psoriatic arthritis, rheumatoid arthritis,
moderately to severely active ulcerative colitis and adults and
adolescents with atopic dermatitis.1,11-15
Use of upadacitinib in Crohn's disease is approved in
Great Britain as of January 2023. Its safety and efficacy remain
under evaluation in the European Union.
About Crohn's Disease
Crohn's disease is a chronic,
systemic disease that manifests as inflammation within the
gastrointestinal tract, causing persistent diarrhea and abdominal
pain.5,6 It is a progressive disease, meaning it gets
worse over time in a substantial proportion of patients or may
develop complications that require urgent medical care, including
surgery.5,6 Because the signs and symptoms of
Crohn's disease are unpredictable, it causes a significant burden
on people living with the disease—not only physically, but also
emotionally and economically.5,6
About the U-EXCEED and U-EXCEL Inductions Studies, and the
U-ENDURE Maintenance Study 1-4
The three Phase 3
studies are multicenter, randomized, double-blind,
placebo-controlled studies to evaluate the efficacy and safety of
upadacitinib 45 mg as induction therapy and upadacitinib 15 mg and
30 mg as maintenance therapy in patients with moderately to
severely active Crohn's disease. Topline results of the U-EXCEED
and U-EXCEL induction studies were announced in December
2021 and February 2022. Topline
results of the U-ENDURE maintenance study were announced in
May 2022. More information can be
found
on www.clinicaltrials.gov (U-EXCEED: NCT03345836,
U-EXCEL: NCT03345849, U-ENDURE: NCT03345823).
About Upadacitinib (RINVOQ®)
Discovered and developed by AbbVie scientists, upadacitinib
(RINVOQ) is a selective and reversible Janus Kinase (JAK)
inhibitor.1 In human cellular assays, upadacitinib
preferentially inhibits signaling by JAK1 or JAK1/3 with functional
selectivity over cytokine receptors that signal via pairs of
JAK2.1
Phase 3 trials of RINVOQ in Crohn's disease, giant cell
arteritis and Takayasu arteritis are ongoing.1,16-18
EU Indications and Important Safety Information about
Upadacitinib (RINVOQ®)1
Indications
Rheumatoid arthritis
RINVOQ is indicated for the treatment of moderate to severe
active rheumatoid arthritis (RA) in adult patients who have
responded inadequately to, or who are intolerant to one or more
disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used
as monotherapy or in combination with methotrexate.
Psoriatic arthritis
RINVOQ is indicated for the treatment of active psoriatic
arthritis (PsA) in adult patients who have responded inadequately
to, or who are intolerant to one or more DMARDs. RINVOQ may be used
as monotherapy or in combination with methotrexate.
Axial spondyloarthritis
Non-radiographic axial spondyloarthritis
(nr-axSpA)
RINVOQ is indicated for the treatment of active non-radiographic
axial spondyloarthritis in adult patients with objective signs of
inflammation as indicated by elevated C-reactive protein (CRP)
and/or magnetic resonance imaging (MRI), who have responded
inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs).
Ankylosing spondylitis (AS, radiographic axial
spondyloarthritis)
RINVOQ is indicated for the treatment of active ankylosing
spondylitis in adult patients who have responded inadequately to
conventional therapy.
Atopic dermatitis
RINVOQ is indicated for the treatment of moderate to severe
atopic dermatitis (AD) in adults and adolescents 12 years and older
who are candidates for systemic therapy.
Ulcerative colitis
RINVOQ is indicated for the treatment of adult patients with
moderately to severely active ulcerative colitis (UC) who have had
an inadequate response, lost response or were intolerant to either
conventional therapy or a biologic agent.
Important Safety
Information
Contraindications
RINVOQ is contraindicated in
patients hypersensitive to the active substance or to any of the
excipients, in patients with active tuberculosis (TB) or active
serious infections, in patients with severe hepatic impairment, and
during pregnancy.
Special warnings and precautions
for use
Immunosuppressive medicinal products
Use in combination with other potent immunosuppressants is not
recommended.
Serious infections
Serious and sometimes fatal
infections have been reported in patients receiving upadacitinib.
The most frequent serious infections reported included pneumonia
and cellulitis. Cases of bacterial meningitis have been reported.
Among opportunistic infections, TB, multidermatomal herpes zoster,
oral/esophageal candidiasis, and cryptococcosis have been reported
with upadacitinib. As there is a higher incidence of infections in
patients ≥65 years of age, caution should be used when treating
this population. Upadacitinib should be interrupted if a patient
develops a serious or opportunistic infection.
Tuberculosis
Patients should be screened for TB before
starting upadacitinib. Upadacitinib should not be given to patients
with active TB. Anti-TB therapy may be appropriate for select
patients in consultation with a physician with expertise in the
treatment of TB. Patients should be monitored for the development
of signs and symptoms of TB.
Viral reactivation
Viral reactivation, including cases
of herpes zoster, was reported in clinical studies. The risk of
herpes zoster appears to be higher in Japanese patients treated
with upadacitinib. Consider interruption of upadacitinib if the
patient develops herpes zoster.
Vaccinations
The use of live, attenuated vaccines
during or immediately prior to therapy is not recommended. It is
recommended that patients be brought up to date with all
immunizations, including prophylactic zoster vaccinations, prior to
initiating upadacitinib, in agreement with current immunization
guidelines.
Malignancy
The risk of malignancies, including
lymphoma is increased in patients with rheumatoid arthritis (RA).
Malignancies, including nonmelanoma skin cancer (NMSC), have been
reported in patients treated with upadacitinib. Consider the risks
and benefits of upadacitinib treatment prior to initiating therapy
in patients with a known malignancy other than a successfully
treated NMSC or when considering continuing upadacitinib therapy in
patients who develop a malignancy. Periodic skin examination is
recommended for patients who are at increased risk for skin
cancer.
Hematological abnormalities
Treatment should not be
initiated, or should be temporarily interrupted, in patients with
hematological abnormalities observed during routine patient
management.
Diverticulitis
Upadacitinib should be used with
caution in patients with diverticular disease and especially in
patients chronically treated with concomitant medications
associated with an increased risk of diverticulitis.
Cardiovascular risk
RA patients have an increased risk
for cardiovascular disorders. Patients treated with upadacitinib
should have risk factors (e.g., hypertension, hyperlipidemia)
managed as part of usual standard of care.
Lipids
Upadacitinib treatment was associated with
dose-dependent increases in lipid parameters, including total
cholesterol, low-density lipoprotein cholesterol, and high-density
lipoprotein cholesterol.
Hepatic transaminase elevations
Treatment with
upadacitinib was associated with an increased incidence of liver
enzyme elevation. If alanine transaminase (ALT) or aspartate
transaminase (AST) increases are observed and drug-induced liver
injury is suspected, upadacitinib should be interrupted until this
diagnosis is excluded.
Venous thromboembolisms
Events of deep vein thrombosis
(DVT) and pulmonary embolism (PE) have been reported in patients
receiving JAK inhibitors, including upadacitinib. Upadacitinib
should be used with caution in patients at high risk for DVT/PE. If
clinical features of DVT/PE occur, upadacitinib should be
discontinued and patients should be evaluated and treated
appropriately.
Elderly
There is an increased risk of adverse
reactions with the upadacitinib dose of 30 mg once daily in
patients aged 65 years and older. The recommended dose for
long-term use is 15 mg once daily for this patient population.
Hypersensitivity reactions
Serious hypersensitivity
reactions such as anaphylaxis and angioedema have been reported in
patients receiving upadacitinib. If a clinically significant
hypersensitivity reaction occurs, discontinue upadacitinib and
institute appropriate therapy.
Adverse reactions
The most commonly reported adverse
reactions in RA, PsA, and axSpA clinical trials (≥2% of patients in
at least one of the indications) with upadacitinib 15 mg were upper
respiratory tract infections, blood creatine phosphokinase (CPK)
increased, ALT increased, bronchitis, nausea, neutropenia, cough,
AST increased, and hypercholesterolemia. Overall, the safety
profile observed in patients with psoriatic arthritis or active
axial spondyloarthritis treated with RINVOQ 15 mg was consistent
with the safety profile observed in patients with RA.
The most commonly reported adverse reactions in atopic
dermatitis trials (≥2% of patients) with RINVOQ 15 mg or 30 mg were
upper respiratory tract infection, acne, herpes simplex, headache,
CPK increased, cough, folliculitis, abdominal pain, nausea,
neutropenia, pyrexia, and influenza. Dose-dependent increased risks
of infection and herpes zoster were observed with upadacitinib. The
safety profile for upadacitinib 15 mg in adolescents was similar to
that in adults. The safety and efficacy of the 30 mg dose in
adolescents are still being investigated.
The most commonly reported adverse reactions in UC trials (≥3%
of patients) with upadacitinib 45 mg, 30 mg or 15 mg were upper
respiratory tract infection, blood CPK increased, acne,
neutropenia, rash, herpes zoster, hypercholesterolemia,
folliculitis, herpes simplex, and influenza. The overall safety
profile observed in patients with ulcerative colitis was generally
consistent with that observed in patients with RA.
The most common serious adverse reactions were serious
infections.
The safety profile of upadacitinib with long-term treatment was
generally similar to the safety profile during the
placebo-controlled period across indications.
This is not a complete summary of all safety
information.
See RINVOQ full Summary of Product Characteristics (SmPC)
at www.ema.europa.eu
Globally, prescribing information varies; refer to the
individual country product label for complete information.
About AbbVie in Gastroenterology
With a robust
clinical trial program, AbbVie is committed to cutting-edge
research to drive exciting developments in inflammatory bowel
diseases (IBD), like ulcerative colitis and Crohn's disease. By
innovating, learning and adapting, AbbVie aspires to eliminate the
burden of IBD and make a positive long-term impact on the lives of
people with IBD. For more information on AbbVie in
gastroenterology,
visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/gastroenterology.html.
About AbbVie
AbbVie's mission is to discover and
deliver innovative medicines that solve serious health issues today
and address the medical challenges of tomorrow. We strive to have a
remarkable impact on people's lives across several key therapeutic
areas: immunology, oncology, neuroscience, eye care, virology,
women's health and gastroenterology, in addition to products and
services across our Allergan Aesthetics portfolio. For more
information about AbbVie, please visit us at www.abbvie.com.
Follow @abbvie
on Twitter, Facebook, LinkedIn or Instagram.
Forward-Looking Statements
Some statements in this
news release are, or may be considered, forward-looking statements
for purposes of the Private Securities Litigation Reform Act of
1995. The words "believe," "expect," "anticipate," "project" and
similar expressions, among others, generally identify
forward-looking statements. AbbVie cautions that these
forward-looking statements are subject to risks and uncertainties
that may cause actual results to differ materially from those
indicated in the forward-looking statements. Such risks and
uncertainties include, but are not limited to, failure to realize
the expected benefits from AbbVie's acquisition of Allergan plc
("Allergan"), failure to promptly and effectively integrate
Allergan's businesses, competition from other products, challenges
to intellectual property, difficulties inherent in the research and
development process, adverse litigation or government action,
changes to laws and regulations applicable to our industry and the
impact of public health outbreaks, epidemics or pandemics, such as
COVID-19. Additional information about the economic, competitive,
governmental, technological and other factors that may affect
AbbVie's operations is set forth in Item 1A, "Risk Factors," of
AbbVie's 2021 Annual Report on Form 10-K, which has been filed with
the Securities and Exchange Commission, as updated by its
subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no
obligation to release publicly any revisions to forward-looking
statements as a result of subsequent events or developments, except
as required by law.
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* Mucosal healing was a prespecified endpoint, not controlled
for multiplicity.
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