- CHMP positive opinion is based on results from the Phase 3
SELECT-AXIS 2 study showing upadacitinib
(RINVOQ®) met the primary endpoint of ASAS40
response at week 14 versus placebo1
- Non-radiographic axial spondyloarthritis (nr-axSpA) is part
of the axial spondyloarthritis (axSpA) spectrum and causes
inflammation in the spine, leading to back pain and
stiffness2,3,4
- The EC decision is expected in the third quarter of
2022
NORTH
CHICAGO, Ill., June 27,
2022 /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® 15 mg, once daily) 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).*
"Patients with axSpA often experience delayed diagnosis and once
they do receive a diagnosis, there are limited therapies available
to help control disease symptoms, such as inflammation, back pain
and stiffness," said Neil Gallagher,
M.D., Ph.D., vice president, development, chief medical officer,
AbbVie. "The CHMP's recommendation to approve upadacitinib for
patients with nr-axSpA is an important milestone in providing a new
treatment option to patients in need."
The CHMP positive opinion is a scientific recommendation for
marketing authorization to the European Commission (EC), which will
review it and issue a Commission decision that will be valid in all
member states of the European Union (EU), as well
as Iceland, Liechtenstein, Northern Ireland and Norway.
AbbVie's application for the approval of upadacitinib in
nr-axSpA is supported by results from the Phase 3 SELECT-AXIS 2
study, for which AbbVie disclosed topline results in 2021. In the
Phase 3 clinical study, the SELECT-AXIS 2 nr-axSpA study met the
primary endpoint of Assessment of SpondyloArthritis international
Society 40 percent response criteria (ASAS40), and the first 12 of
14 ranked secondary endpoints.1 Safety data were
previously reported with no new risks identified compared to the
known safety profile of upadacitinib.1
Upadacitinib is currently approved for use in the EU in patients
with moderate to severe active rheumatoid arthritis, active
psoriatic arthritis, active ankylosing spondylitis, and moderate to
severe atopic dermatitis.5
The use of upadacitinib in nr-axSpA is not approved in the U.S.
or EU. Its efficacy and safety remain under review.
About the SELECT-AXIS 2 program
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).
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.
Study 1: SELECT-AXIS 2 AS (bDMARD-IR) study6
A randomized, double-blind, placebo-controlled Phase 3 trial,
which evaluated the efficacy and safety of upadacitinib 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 study1
A randomized, double-blind, placebo-controlled, Phase 3 trial
which evaluated the efficacy and safety of upadacitinib 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).
About Axial Spondyloarthritis (axSpA)
Axial spondyloarthritis is a chronic inflammatory disease that
affects the spine, causing back pain, limited mobility, and
structural damage.4 It consists of two subsets that
have been clinically defined as radiographic axial SpA (ankylosing
spondylitis) and non-radiographic axial spondyloarthritis
(nr-axSpA).4 In ankylosing spondylitis, patients
have definitive structural damage of the sacroiliac joints visible
on X-rays.4 Non-radiographic axial
spondyloarthritis is clinically defined by the absence of
definitive X-ray evidence of structural damage to the sacroiliac
joint by plain X-ray.4
About
RINVOQ® (upadacitinib)5
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 JAK2.5
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 ankylosing spondylitis (AS) in adult
patients who have responded inadequately to conventional therapy;
and for adults (15 mg and 30 mg) and adolescents (15 mg) with
moderate to severe atopic dermatitis.5
Phase 3 trials of RINVOQ in axial spondyloarthritis, Crohn's
disease, giant cell arteritis and Takayasu arteritis are
ongoing.7,8,9,10 Use of RINVOQ in nr-axSpA is not
approved and remains under review by regulatory authorities.
EU Indications and Important Safety Information about
RINVOQ® (upadacitinib)5
Indications
Rheumatoid arthritis
RINVOQ is indicated for the treatment of moderate to severe
active rheumatoid arthritis 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 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.
Ankylosing spondylitis
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 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.
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.
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.
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 compared to placebo.
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.
Adverse reactions
The most commonly reported adverse
reactions in rheumatoid arthritis, psoriatic arthritis, and
ankylosing spondylitis 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, alanine transaminase (ALT) increased, bronchitis,
nausea, cough, aspartate transaminase (AST) increased, and
hypercholesterolemia.
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. 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.
Overall, the safety profile observed in patients with psoriatic
arthritis or active ankylosing spondylitis treated with
upadacitinib 15 mg was consistent with the safety profile observed
in patients with RA. In atopic dermatitis, dose-dependent increased
risks of infection and herpes zoster were observed with
upadacitinib. Based on limited data, there was a higher rate of
overall adverse reactions with the upadacitinib 30 mg dose compared
to the 15 mg dose in patients aged 65 years and older.
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. Dose-dependent
changes in ALT increased and/or AST increased (≥ 3 x ULN), lipid
parameters, CPK values (> 5 x ULN), and neutropenia (ANC < 1
x 109 cells/L) associated with upadacitinib treatment
were similar to what was observed in the rheumatologic disease
clinical studies.
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.
References
1 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.
2 Crossfield SSR, Marzo-Ortega H, Kingbury 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.
3 Mayo Clinic. Ankylosing Spondylitis 2019. Available
at:
https://www.mayoclinic.org/diseases-conditions/ankylosing-spondylitis/symptomscauses/syc-20354808.
Accessed April 2022.
4 Deodhar AA, Understanding Axial
Spondyloarthritis: A Primer for Managed Care. Am J Managed Care.
2019;25:S319-S330.
5 RINVOQ [Summary of Product Characteristics]. AbbVie
Deutschland GmbH & Co. KG; May
2022. Available at:
https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
Accessed June 14, 2022.
6 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.
7 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
on April 1, 2022.
8 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
on April 1, 2022.
9 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
on April 1, 2022.
10 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
on April 1, 2022.
*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
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content:https://www.prnewswire.com/news-releases/chmp-recommends-approval-of-upadacitinib-rinvoq-for-the-treatment-of-adults-with-active-non-radiographic-axial-spondyloarthritis-301574375.html
SOURCE AbbVie