- Results from the SELECT-AXIS 2 non-radiographic axial
spondyloarthritis (nr-axSpA) study demonstrated significantly
greater improvements in signs and symptoms, pain, function, disease
activity, health-related quality of life, and MRI-detected SI joint
inflammation with upadacitinib
(RINVOQ®) compared to placebo at
week 141
- Results from the SELECT-AXIS 2 ankylosing spondylitis (AS)
bDMARD-IR study demonstrated significantly greater improvements in
signs and symptoms, pain, function, disease activity,
health-related quality of life, and MRI-detected spine inflammation
with upadacitinib compared to placebo at week
142
- Safety data were consistent with the known safety profile of
upadacitinib, with no new risks
observed1,2,3,4,5
NORTH
CHICAGO, Ill., June 1, 2022
/PRNewswire/ -- AbbVie (NYSE: ABBV) today announced the
presentation of full results from two studies from the Phase 3
SELECT-AXIS 2 program evaluating upadacitinib
(RINVOQ®), an oral therapy, in adult patients
with active non-radiographic axial spondyloarthritis (nr-axSpA) and
patients with treatment-refractory active ankylosing spondylitis
(AS) with an inadequate response (IR) to biologic disease-modifying
antirheumatic drugs (bDMARDs). Both studies met the primary
endpoint of Assessment of SpondyloArthritis international Society
40 percent response criteria (ASAS40) at week 14 versus
placebo.1,2
In the SELECT-AXIS 2 nr-axSpA study, significantly more nr-axSpA
patients achieved the primary endpoint of ASAS40 at week 14 with
upadacitinib versus placebo (45 percent versus 23 percent;
p<0.0001).1 Statistical significance was also
achieved in the first 12 of 14 multiplicity-controlled secondary
endpoints compared to placebo at week 14 including change from
baseline in patient's assessment of total back pain, Bath
Ankylosing Spondylitis Functional Index (BASFI), Ankylosing
Spondylitis Disease Activity Score (ASDAS) Low Disease Activity,
Ankylosing Spondylitis Quality of Life (ASQoL), and MRI
Spondyloarthritis Research Consortium of Canada (SPARCC) score for SI
joints.1
"The new data observed from SELECT-AXIS 2 reinforce the
potential of upadacitinib for patients across the spectrum of axial
spondyloarthritis disease," said Neil
Gallagher, M.D., Ph.D., vice president, development, chief
medical officer, AbbVie. "At AbbVie, the needs of patients drive us
to continue to innovate new ways to change the treatment landscape.
We are encouraged by these positive data, which we hope will lead
to the availability of a new treatment option for patients with
nr-axSpA."
These findings, for which AbbVie disclosed topline results in
2021, were submitted as part of the regulatory applications to the
U.S. Food and Drug Administration (FDA) and the European Medicines
Agency (EMA) to treat adults with active nr-axSpA with objective
signs of inflammation who have responded inadequately to
nonsteroidal anti-inflammatory drugs (NSAIDs).
"Non-radiographic axial spondyloarthritis is a progressive and
disabling inflammatory disease, with limited treatment options.
It often affects young adults, causing spinal inflammation
that leads to back pain and stiffness and can significantly
decrease quality of life," 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.* "These data suggest the potential of
upadacitinib to help counter inflammation, relieve pain and improve
function, helping patients living with nr-axSpA take control of
their disease."
In the SELECT-AXIS 2 AS bDMARD-IR study, significantly more
patients achieved the primary endpoint of ASAS40 at week 14 with
upadacitinib versus placebo (45 percent versus 18 percent;
p<0.0001).2 Statistical significance was also
achieved in all multiplicity-controlled secondary endpoints
compared to placebo at week 14, including change from baseline in
patient's assessment of total back pain, BASFI, ASDAS low disease
activity, ASQoL, and MRI SPARCC score for
spine.2
No new safety risks were identified with upadacitinib when
compared with its known safety
profile.1,2,3,4,5 Through
week 14 in the nr-axSpA study, the proportion of patients who
experienced an adverse event (AE) was similar between both
treatment groups (upadacitinib at 48 percent and placebo at 46
percent).1 Serious AEs were reported in four
patients on upadacitinib and in two patients on
placebo.1 Through week 14 in the AS bDMARD-IR
study, the proportion of patients who experienced an adverse event
was also similar (upadacitinib at 41 percent and placebo at 37
percent).2 In both the nr-axSpA study and the AS
bDMARD-IR study, there were no reports of malignancy, major adverse
cardiovascular events, venous thromboembolic events or death in
patients receiving
upadacitinib.1,2
The full results for both studies will be presented at the EULAR
2022 Congress. The SELECT-AXIS 2 nr-axSpA study results will be
presented in an oral presentation on 1 June, 4:35 – 4:45pm (CEST)
(OP0016) and the SELECT-AXIS 2 AS bDMARD-IR study results will be
presented in a poster tour on 4 June, 11:37 – 11:45am (CEST)
(POS0306).
Use of upadacitinib in nr-axSpA is not approved in the U.S. or
EU, and its efficacy and safety are currently under review by the
respective regulatory authorities.
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). AbbVie previously announced topline data showing
that upadacitinib 15 mg met the primary endpoint vs placebo at week
14 in Study 1 and Study 2.
More information on the SELECT-AXIS 2 program is available
at www.clinicaltrials.gov (NCT04169373).
Study 1: SELECT-AXIS 2 bDMARD-IR AS study1
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 study2
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 consistent with axSpA on MRI of the sacroiliac (SI)
joints, 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).
*Dr. Van den Bosch is a
consultant and advisor for AbbVie.
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.6 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)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.
Phase 3 trials of RINVOQ in atopic dermatitis, axial
spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell
arteritis and Takayasu arteritis are
ongoing.7,8,9,10,11,12 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 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.
3 Cohen et al. Ann Rheum Dis. 2020 Oct
28;80(3):304-11.
4 Burmester et al. Rheumatol Ther.
2022;9(2):521-39.
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 May 2022.
6 Deodhar AA, Understanding Axial
Spondyloarthritis: A Primer for Managed Care. Am J Managed Care.
2019;25:S319-S330.
7 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 on
April 1, 2022.
8 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.
9 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.
10 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 on
April 1, 2022.
11 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.
12 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.
View original
content:https://www.prnewswire.com/news-releases/abbvie-presents-positive-results-from-phase-3-select-axis-2-trials-of-upadacitinib-rinvoq-in-patients-with-axial-spondyloarthritis-at-eular-2022-301558026.html
SOURCE AbbVie