- With this approval, RINVOQ® (upadacitinib 15 mg,
once daily) is the first and only Janus Kinase (JAK) inhibitor
approved to treat patients across the spectrum of axial
spondyloarthritis (nr-axSpA and ankylosing spondylitis) in the
European Union (EU)1
- Approval is supported by data from the Phase 3 SELECT-AXIS 2
pivotal clinical trial in which RINVOQ delivered meaningful disease
control with nearly half of nr-axSpA patients achieving ASAS40 at
week 14 (45 percent versus 23 percent; p<0.0001) compared to
placebo2
NORTH
CHICAGO, Ill., July 29,
2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced
that the European Commission (EC) has approved RINVOQ®
(upadacitinib 15 mg, once daily), an oral therapy, for the
treatment of active non-radiographic axial spondyloarthritis
(nr-axSpA) 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).*1
"For years, healthcare providers and patients have had limited
treatment options to manage axial spondyloarthritis, which can
cause back pain, stiffness, and irreversible damage to the spine,"
said Thomas Hudson, M.D., senior
vice president of research and development, chief scientific
officer, AbbVie. "AbbVie is proud to offer RINVOQ as a
first-in-class treatment option now approved in the European Union
for adults living with nr-axSpA with objective signs of
inflammation and inadequate response to NSAIDs. RINVOQ is the first
and only JAK inhibitor approved to treat patients across the
spectrum of axial spondyloarthritis, which includes nr-axSpA and
ankylosing spondylitis."
Axial spondyloarthritis (axSpA) is a chronic, progressive and
disabling inflammatory rheumatic disease that causes joint
inflammation, leading to back pain and stiffness.3,4,5
AxSpA consists of two subsets that have been clinically defined as
ankylosing spondylitis (AS), also known as radiographic axial
spondyloarthritis (r-axSpA), and non-radiographic axial
spondyloarthritis (nr-axSpA).6 Approximately 10-40
percent of patients eventually progress from nr-axSpA to r-axSpA
over a 2- to 10-year period.7
"The European Commission's approval of RINVOQ for the treatment
of nr-axSpA offers physicians in the European Union an important
new therapeutic option with proven efficacy in both nr-axSpA and AS
patient populations," said Filip Van den
Bosch, M.D.,** SELECT-AXIS 2 investigator and professor in
the Department of Rheumatology at the University Hospital of Ghent
University. "Living with nr-axSpA can pose many challenges and
significantly impact a patient's quality of life. Early and
effective disease management of patients with active nr-axSpA is
key to improving health outcomes."
AbbVie previously disclosed topline results from the Phase
3 SELECT-AXIS 2 nr-axSpA clinical trial and the full results have
been published in The Lancet. Study results show a
significantly greater proportion of patients receiving RINVOQ 15 mg
achieved an Assessment of SpondyloArthritis international Society
40 percent (ASAS40) response at week 14 (45 percent versus 23
percent; p<0.0001) compared to
placebo.2 Statistical significance was also
achieved in 12 of the 14 multiplicity-controlled secondary
endpoints compared to placebo at week 14.2 Safety
data were previously reported with no new risks identified compared
to the known safety profile of RINVOQ.2 Through
week 14, the proportion of patients who experienced an adverse
event (AE) was similar between treatment groups (RINVOQ at 48
percent and placebo at 46 percent).2
The EC Marketing Authorization for nr-axSpA means that RINVOQ is
approved in all member states of the European Union, as well as
Iceland, Liechtenstein, Northern Ireland and Norway.
RINVOQ also recently received a label enhancement in the EU for
the already approved indication of AS to include data on patients
with active AS who had an inadequate response to biologic
disease-modifying anti-rheumatic drugs (bDMARDs) based on the
results of the Phase 3 SELECT-AXIS 2 clinical trial in this
population, as well as two-year results of the Phase 2/3
SELECT-AXIS 1 clinical trial that evaluated AS bDMARD-naïve
patients.8,9
AbbVie previously disclosed topline results from the Phase
3 SELECT-AXIS 2 AS bDMARD-IR study, in which a significantly
greater proportion of patients receiving RINVOQ 15 mg achieved an
ASAS40 response at week 14 (45 percent versus 18 percent) compared
to placebo.8 All 14 ranked secondary endpoints were
met including those evaluating improvements from baseline in
disease activity, pain (total and nocturnal back pain), function,
MRI SPARCC score (spine), spinal mobility, enthesitis, and
health-related quality of life.8 Safety data
were previously reported with no new risks identified compared to
the known safety profile of RINVOQ.8 Through week
14, the proportion of patients who experienced an AE was similar
between treatment groups (RINVOQ at 41 percent and placebo at 37
percent).8
About the SELECT-AXIS 1 and SELECT-AXIS 2 trial
programs2,8,9
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 AS who are bDMARD-naïve and had inadequate response to
at least two NSAIDs or intolerance to/contraindication for NSAIDs.
Period 2 is an open-label extension period to evaluate the
long-term safety and efficacy of RINVOQ in subjects who completed
Period 1. More information on this trial can be found at
www.clinicaltrialsregister.eu/ (2017-000431-14) in the EU, and at
www.clinicaltrials.gov (NCT03178487) in the U.S.
SELECT-AXIS 2 (NCT04169373) was conducted under a master
protocol and includes two separate studies (SELECT-AXIS 2 AS
(bDMARD-IR) study, or Study 1 and SELECT-AXIS 2 nr-axSpA study, or
Study 2).
Study 1: SELECT-AXIS 2 AS (bDMARD-IR) study8
A randomized, double-blind, placebo-controlled Phase 3 trial,
which evaluated the efficacy and safety of RINVOQ compared with
placebo, in 420 patients with a clinical diagnosis of AS who
fulfilled the modified New York
criteria, had BASDAI score ≥4 and total back pain score ≥4 (based
on a numerical scale of 0-10), and had an inadequate response to
bDMARD therapy.
Study 2: SELECT-AXIS 2 nr-axSpA study2
A randomized, double-blind, placebo-controlled, Phase 3 trial
which evaluated the efficacy and safety of RINVOQ compared with
placebo, in 314 patients with a clinical diagnosis of nr-axSpA.
Patients enrolled in the study had active signs of inflammation as
indicated by MRI + sacroiliac joint inflammation, and/or high
sensitivity C-reactive protein (hs-CRP) >upper limit of normal
(2.87 mg/L) at screening, and who had BASDAI score ≥4 and a total
back pain score ≥4 (based on a numerical scale of 0-10).
More information on the SELECT-AXIS 2 program is
available at
https://www.clinicaltrialsregister.eu/ (2019-003229-12) in
the EU, and at www.clinicaltrials.gov (NCT04169373) in
the U.S.
About Axial Spondyloarthritis (axSpA)
Axial spondyloarthritis is a chronic inflammatory disease that
affects the spine, causing back pain, limited mobility, and
structural damage.6 It consists of two subsets that
have been clinically defined as radiographic axial SpA (ankylosing
spondylitis) and non-radiographic axial spondyloarthritis
(nr-axSpA).6 In ankylosing spondylitis, patients
have definitive structural damage of the sacroiliac joints visible
on X-rays. Non-radiographic axial spondyloarthritis is
clinically defined by the absence of definitive X-ray evidence of
structural damage to the sacroiliac (SI) joint by plain
X-ray.6
About
RINVOQ® (upadacitinib)1
Discovered and developed by AbbVie scientists, RINVOQ is a
selective JAK inhibitor that is being studied in several
immune-mediated inflammatory diseases. In human cellular assays,
RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with
functional selectivity over cytokine receptors that signal via
pairs of JAK2.
In the EU, RINVOQ is approved for the treatment of adults 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; 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; for
the treatment of active non-radiographic axial spondyloarthritis in
adult patients with objective signs of inflammation as indicated by
elevated CRP and/or MRI, who have responded inadequately to NSAIDs;
for the treatment of active ankylosing spondylitis (AS) in adult
patients who have responded inadequately to conventional therapy;
for adults (15 mg and 30 mg) and adolescents (15 mg) with moderate
to severe atopic dermatitis; and 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.1
Phase 3 trials of RINVOQ in atopic dermatitis, axial
spondyloarthritis, Crohn's disease, giant cell arteritis and
Takayasu arteritis are ongoing.10,11,12,13,14,15
EU Indications and Important Safety Information about
RINVOQ® (upadacitinib)1
Indications
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.
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.
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 RINVOQ.
RINVOQ 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 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.
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, cough, AST increased, and
hypercholesterolemia. Overall, the safety profile observed in
patients with psoriatic arthritis or active axial spondyloarthritis
treated with upadacitinib 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 upadacitinib 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,
neutropaenia, 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/en.
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
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.
*This recommendation is without prejudice to the final
conclusions of the ongoing referral procedure under Article 20 of
Regulation (EC) No 726/2004 resulting from pharmacovigilance
data.
**Dr. Van den Bosch is a
consultant and advisor for AbbVie.
References:
1 AbbVie, Ltd. RINVOQ (upadacitinib)
[summary of product characteristics].
https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
Accessed July 28, 2022.
2 Deodhar, A, et al. Efficacy and Safety of
Upadacitinib in Patients with Active Non-Radiographic Axial
Spondyloarthritis: a Double-Blind, Randomized, Placebo-Controlled
Phase 3 Trial. EULAR 2022 Congress; 2534.
3 Crossfield SSR, Marzo-Ortega H, Kingsbury SR, et
al. Changes in ankylosing spondylitis incidence, prevalence and
time to diagnosis over two decades. RMD Open 2021;7:e001888.
doi: 10.1136/rmdopen-2021-001888.
4 Mayo Clinic. Ankylosing Spondylitis. 2019.
Available at:
https://www.mayoclinic.org/diseases-conditions/ankylosing-spondylitis/symptoms-causes/syc-20354808.
Accessed June 2022.
5 Dean, LE, et al. Global prevalence of ankylosing
spondylitis. Rheumatology (Oxford). 2014 Apr;53(4):650-7. doi:
10.1093/rheumatology/ket387. Epub 2013
6 Deodhar AA, Understanding Axial Spondyloarthritis:
A Primer for Managed Care. Am J Manag Care. 2019;25:S319-S330.
7 Protopopov M, Poddubnyy D. Radiographic progression
in non-radiographic axial spondyloarthritis. Expert Rev
Clin Immunol.
2018;14(6):525-533.
8 Van der Heijde, D,
et al. Efficacy and Safety of Upadacitinib in Patients With Active
Ankylosing Spondylitis Refractory to Biologic Therapy: a
Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial. EULAR
2022 Congress; 2518.
9 Van der Heijde D, et al. Efficacy and Safety of
Upadacitinib in Patients with Active Ankylosing Spondylitis: 2-Year
Results from a Randomized, Double-Blind, Placebo-Controlled Study
with Open-Label Extension [abstract]. Arthritis Rheumatol. 2021; 73
(suppl 10).
10 Evaluation of Upadacitinib in Adolescent and Adult
Patients With Moderate to Severe Atopic Dermatitis (Eczema)
(Measure Up 1). ClinicalTrials.gov. 2021. Available at:
https://clinicaltrials.gov/ct2/show/NCT03569293. Accessed
June 2022.
11 A Study to Evaluate Efficacy and Safety of
Upadacitinib in Adult Participants With Axial Spondyloarthritis
(SELECT-AXIS 2). ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed
June 2022.
12 A Study of the Efficacy and Safety of Upadacitinib
(ABT-494) in Participants With Moderately to Severely Active
Crohn's Disease Who Have Inadequately Responded to or Are
Intolerant to Biologic Therapy. ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT03345836. Accessed
June 2022.
13 A Study to Evaluate the Safety and Efficacy of
Upadacitinib (ABT-494) for Induction and Maintenance Therapy in
Participants With Moderately to Severely Active Ulcerative Colitis
(UC). ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed
June 2022.
14 A Study to Evaluate the Safety and Efficacy of
Upadacitinib in Participants With Giant Cell Arteritis
(SELECT-GCA). ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed
June 2022.
15 A Study to Evaluate the Efficacy and Safety of
Upadacitinib in Subjects With Takayasu Arteritis (TAK)
(SELECT-TAK). ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT04161898. Accessed
June 2022.
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