NORTH CHICAGO, Ill.,
Dec. 11, 2020 /PRNewswire/
-- AbbVie (NYSE: ABBV) today announced that the European
Medicines Agency's (EMA) Committee for Medicinal Products for Human
Use (CHMP) recommended the approval of RINVOQ™
(upadacitinib, 15 mg), an oral, once daily selective and reversible
JAK inhibitor, for the expanded use in two additional rheumatic
indications: the treatment of adult patients with active psoriatic
arthritis and adult patients with active ankylosing
spondylitis.5 The CHMP positive opinions are based on
results from three pivotal clinical studies in which RINVOQ
demonstrated efficacy across multiple measures of disease
activity.1-3
"The CHMP's recommendations to approve RINVOQ in both psoriatic
arthritis and ankylosing spondylitis mark an important milestone.
AbbVie is committed to continued research to advance treatment
standards for patients living with these debilitating diseases,"
said Thomas Hudson, senior vice
president, research and development, AbbVie. "If approved, RINVOQ
will become an oral, once daily targeted treatment option across
three rheumatic indications in the European Union. These
recommendations pave the path towards helping more people living
with psoriatic arthritis and ankylosing spondylitis find relief
from their symptoms across multiple manifestations of the
diseases."
In both the Phase 3 SELECT-PsA 1 and SELECT-PsA 2 clinical
trials, RINVOQ met the primary endpoint of ACR20 response at week
12 versus placebo in adult patients with active psoriatic arthritis
who had an inadequate response to non-biologic disease-modifying
antirheumatic drugs (DMARDs) or biologic DMARDs,
respectively.1,2
RINVOQ also met the primary endpoint of Assessment of
Spondyloarthritis International Society (ASAS) 40 response at week
14 versus placebo in SELECT-AXIS 1, a Phase 2/3 study in patients
who were naïve to biologic DMARDs and had an inadequate response or
intolerance to nonsteroidal anti-inflammatory drugs
(NSAIDs).3
Safety results from SELECT-PsA 1, SELECT-PsA 2 and SELECT-AXIS 1
have been previously reported and were consistent with those
observed in rheumatoid arthritis, with no new significant safety
risks identified.1-4
The CHMP positive opinion is a scientific recommendation for
marketing authorization to the European Commission, which
authorizes marketing approval in the European Union. The Marketing
Authorization would be valid in all member states of the European
Union, as well as Iceland,
Liechtenstein and Norway.
About Psoriatic Arthritis
Psoriatic arthritis is a heterogeneous, systemic inflammatory
disease with hallmark manifestations across multiple domains
including joints and skin.6,7 In psoriatic arthritis,
the immune system creates inflammation that can lead to skin
lesions associated with psoriasis, pain, fatigue and stiffness in
the joints.6,7
About Ankylosing Spondylitis
Ankylosing spondylitis is a chronic, inflammatory
musculoskeletal disease primarily affecting the spine and
characterized by debilitating symptoms of pain, limited mobility,
structural damage and vertebral fractures.8,9
About SELECT-PsA 11,10
SELECT-PsA 1 is a Phase 3, multicenter, randomized,
double-blind, parallel-group, active and placebo-controlled study
designed to evaluate the safety and efficacy of RINVOQ compared to
placebo and adalimumab in adult patients with active psoriatic
arthritis who have a history of inadequate response to at least one
non-biologic DMARD. Patients were randomized to RINVOQ 15 mg,
RINVOQ 30 mg, adalimumab 40 mg EOW or placebo at baseline. At week
24, placebo patients were switched to either RINVOQ 15 mg or RINVOQ
30 mg.
The primary endpoint was the percentage of subjects receiving
RINVOQ 15 mg or RINVOQ 30 mg who achieved an ACR20 response at 12
weeks of treatment versus placebo. Key secondary endpoints included
change from baseline in HAQ-DI, proportion of patients achieving
ACR50 and ACR70 at week 12, proportion of patients achieving PASI
75 at week 16 and proportion of patients achieving minimal disease
activity (MDA) at week 24. These are not all of the secondary
endpoints. The trial is ongoing, and the long-term extension will
provide data on the long-term safety, tolerability and efficacy of
RINVOQ in patients who have completed the placebo-controlled
period.
Top-line results from SELECT-PsA 1 were previously
announced in February 2020. More
information on this trial can be found
at www.clinicaltrials.gov (NCT03104400).
About SELECT-PsA 22,11
SELECT-PsA 2 is a Phase 3, multicenter, randomized,
double-blind, parallel-group, placebo-controlled study designed to
evaluate the safety and efficacy of RINVOQ in adult patients with
active psoriatic arthritis who have a history of inadequate
response to at least one biologic (bDMARD). Patients were
randomized to RINVOQ 15 mg, RINVOQ 30 mg or placebo followed by
either RINVOQ 15 mg or RINVOQ 30 mg at week 24.
The primary endpoint was the percentage of subjects achieving an
ACR20 response after 12 weeks of treatment. Key secondary endpoints
included change from baseline in HAQ-DI, proportion of patients
achieving ACR50 and ACR70 at week 12, proportion of patients
achieving PASI 75 at week 16, as well as proportion of patients
achieving MDA at week 24. These are not all of the secondary
endpoints. The trial is ongoing, and the long-term extension will
provide data on the long-term safety, tolerability and efficacy of
RINVOQ in patients who have completed the placebo-controlled
period.
Top-line results from SELECT-PsA 2 were previously
announced in October 2019. More
information on this trial can be found
at www.clinicaltrials.gov (NCT03104374).
About SELECT-AXIS 13,12
SELECT-AXIS 1 is a Phase 2/3, multicenter, randomized,
double-blind, parallel-group, placebo-controlled study designed to
evaluate the safety and efficacy of RINVOQ in adult patients with
active ankylosing spondylitis who are bDMARD-naïve and had
inadequate response to at least two NSAIDs or intolerance
to/contraindication for NSAIDs.
Key ranked secondary endpoints included proportion of subjects
achieving Bath Ankylosing Spondylitis Disease Activity Index
(BASDAI) 50 and ASAS partial remission (PR) at week 14, as well as
change from baseline in Ankylosing Spondylitis Disease Activity
Scores (ASDAS), MRI Spondyloarthritis Research Consortium
of Canada (SPARCC) score (spine) and Bath Ankylosing
Spondylitis Functional Index (BASFI) at week 14. Period 2 is an
open-label extension period to evaluate the long-term safety,
tolerability and efficacy of RINVOQ in subjects who completed
Period 1.
Results from SELECT-AXIS 1 were previously announced in
November 2019. More information on
this trial can be found
at www.clinicaltrials.gov (NCT03178487).
About RINVOQ™ (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a
JAK inhibitor that is being studied in several immune-mediated
inflammatory diseases.10-20 In August 2019, RINVOQ
received U.S. FDA approval for adult patients with moderately to
severely active rheumatoid arthritis who have had an inadequate
response or intolerance to methotrexate. In December 2019,
RINVOQ was approved by the European Commission for the treatment of
adult patients with moderate to severe active rheumatoid arthritis
who have responded inadequately to, or who are intolerant to one or
more disease-modifying anti-rheumatic drugs. The approved dose for
RINVOQ in rheumatoid arthritis is 15 mg. Phase 3 trials of RINVOQ
in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis,
axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant
cell arteritis and Takayasu arteritis are
ongoing.10-12,14-20
Important Safety Information about RINVOQ™
(upadacitinib)5
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.
Use in combination with other potent immunosuppressants is not
recommended.
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/oesophageal
candidiasis, and cryptococcosis have been reported with
upadacitinib. Prior to initiating upadacitinib, consider the risks
and benefits of treatment in patients with chronic or recurrent
infection or with a history of a serious or opportunistic
infection, in patients who have been exposed to TB or have resided
or travelled in areas of endemic TB or endemic mycoses, and in
patients with underlying conditions that may predispose them to
infection. Upadacitinib therapy should be interrupted if a patient
develops a serious or opportunistic infection. As there is a higher
incidence of infections in patients ≥75 years of age, caution
should be used when treating this population.
Patients should be screened for TB before starting upadacitinib
therapy. Anti-TB therapy should be considered prior to initiation
of upadacitinib in patients with previously untreated latent TB or
in patients with risk factors for TB infection.
Viral reactivation, including cases of herpes zoster, were
reported in clinical studies. Consider interruption of therapy if a
patient develops herpes zoster until the episode resolves.
Screening for viral hepatitis and monitoring for reactivation
should be performed before starting and during therapy with
upadacitinib.
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.
The risk of malignancies, including lymphoma is increased in
patients with rheumatoid arthritis (RA). Immunomodulatory medicinal
products may increase the risk of malignancies, including lymphoma.
The clinical data are currently limited and long-term studies are
ongoing. Malignancies, including non-melanoma 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.
Absolute neutrophil count <1000 cells/mm3,
absolute lymphocyte count <500 cells/mm3, or
haemoglobin levels <8 g/dL were reported in <1% of
patients in clinical trials. Treatment should not be initiated, or
should be temporarily interrupted, in patients with these
haematological abnormalities observed during routine patient
management.
RA patients have an increased risk for cardiovascular disorders.
Patients treated with upadacitinib should have risk factors (e.g.,
hypertension, hyperlipidaemia) managed as part of usual standard of
care.
Upadacitinib treatment was associated with increases in lipid
parameters, including total cholesterol, low-density lipoprotein
cholesterol, and high-density lipoprotein cholesterol. The effect
of these lipid parameter elevations on cardiovascular morbidity and
mortality has not been determined.
Treatment with upadacitinib was associated with an increased
incidence of liver enzyme elevation compared to placebo. If
increases in ALT or AST are observed during routine patient
management and drug-induced liver injury is suspected, upadacitinib
therapy should be interrupted until this diagnosis is excluded.
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. Risk factors that should be considered in
determining the patient's risk for DVT/PE include older age,
obesity, a medical history of DVT/PE, patients undergoing major
surgery, and prolonged immobilisation. If clinical features of
DVT/PE occur, upadacitinib treatment should be discontinued and
patients should be evaluated promptly, followed by appropriate
treatment.
The most commonly reported adverse drug reactions are upper
respiratory tract infections (13.5%), nausea (3.5%), increased
blood creatine phosphokinase (2.5%), and cough (2.2%). The most
common serious adverse reactions were serious infections.
Please see the full SmPC for complete prescribing information
at www.EMA.europa.eu.
Globally, prescribing information varies; refer to the
individual country product label for complete information.
About AbbVie in Rheumatology
For more than 20 years, AbbVie has been dedicated to improving
care for people living with rheumatic diseases. Our longstanding
commitment to discovering and delivering transformative therapies
is underscored by our pursuit of cutting-edge science that improves
our understanding of promising new pathways and targets in order to
help more people living with rheumatic diseases reach their
treatment goals. For more information on AbbVie in rheumatology,
visit
https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/rheumatology.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 its
Allergan Aesthetics portfolio. For more information about AbbVie,
please visit us at www.abbvie.com. Follow @abbvie on Twitter,
Facebook, Instagram, YouTube and LinkedIn.
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, including the impact of the COVID-19 pandemic on
AbbVie's operations, results and financial results, 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 of
the Allergan acquisition, failure to promptly and effectively
integrate Allergan's businesses, significant transaction costs
and/or unknown or inestimable liabilities, potential litigation
associated with the Allergan acquisition, challenges to
intellectual property, competition from other products,
difficulties inherent in the research and development process,
adverse litigation or government action, and changes to laws and
regulations applicable to our industry. 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 2019 Annual Report on Form
10-K, which has been filed with the Securities and Exchange
Commission (SEC). 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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10.1136/annrheumdis-2020-218870
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