NORTH CHICAGO, Ill.,
Oct. 7, 2021 /PRNewswire/
-- AbbVie (NYSE: ABBV) today announced positive top-line
results from the first of two studies of the Phase 3 SELECT-AXIS 2
clinical trial evaluating the efficacy and safety of
RINVOQ® (upadacitinib; 15 mg, once daily) in patients
with active ankylosing spondylitis (AS) who had an inadequate
response to biologic DMARD therapy. In this study, RINVOQ met
its primary endpoint of Assessment in SpondyloArthritis
International Society (ASAS) 40 response and all ranked secondary
endpoints at week 14.1 Significantly more RINVOQ-treated
patients achieved ASAS40 response at week 14 compared to
placebo (45 percent versus 18 percent;
p<0.0001).1
The results of SELECT-AXIS 1, a Phase 2/3 study in adult
patients with ankylosing spondylitis who were naïve to bDMARDs and
had an inadequate response or intolerance to nonsteroidal
anti-inflammatory drugs (NSAIDs), were used to support
the European Commission approval of RINVOQ for the treatment
of active ankylosing spondylitis in January 2021.6
AbbVie will also announce the positive results of the second
study of SELECT-AXIS 2 in adults with non-radiographic axial
spondyloarthritis (nr-axSpA) later today.1
"Ankylosing spondylitis is a debilitating disease that can cause
severe pain, stiffness, restricted mobility and lasting structural
damage impacting patients' everyday life," said Michael Severino, M.D., vice chairman and
president, AbbVie. "AbbVie is committed to improving standards of
care for patients with rheumatic diseases. We are encouraged by
these results that show RINVOQ was able to provide significant
improvements in signs and symptoms, as well as other measures of
disease activity, for patients living with ankylosing
spondylitis who have already failed treatment with a
biologic."
Treatment with RINVOQ resulted in statistically significant
reductions in signs and symptoms of AS, including back pain and
inflammation, as well as improvements in physical function and
disease activity at week 14.1 Significantly more
patients treated with RINVOQ achieved Ankylosing
Spondylitis Disease Activity Score (ASDAS) Low
Disease Activity compared to those treated with placebo (44 percent
versus 10 percent).1 A statistically significantly
greater improvement in Magnetic Resonance Imaging (MRI)
Spondyloarthritis Research Consortium of Canada (SPARCC) Score (Spine) as measured by
mean change from baseline was reported in the RINVOQ group versus
the placebo group (-3.95 versus -0.04).1 Patients on
RINVOQ experienced a significantly greater mean decrease from
baseline in Patient's Assessment of Total Back Pain at week 14 than
those on placebo (-3.00 versus -1.47).1 Additionally,
patients treated with RINVOQ experienced significantly greater
improvement in physical function as assessed by mean change from
baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
compared to patients on placebo (-2.26 versus
-1.09).1 All ranked secondary endpoints achieved
p-values of <0.0001 versus placebo.1
SELECT-AXIS 2
(Study 1) Efficacy Results at Week 14*,1
|
|
RINVOQ 15 mg, once
daily
(n=211)
|
Placebo
(n=209)
|
Percent of Patients
achieving ASAS40a
|
45%
|
18%
|
Percent of Patients
achieving ASDAS Low Disease Activityb
|
44%
|
10%
|
Mean Change from
Baseline in Magnetic Resonance Imaging (MRI) SPARCC Score
(Spine)c
|
-3.95
|
-0.04
|
Mean Change from
Baseline in Patient's Assessment of Total Back
Paind
|
-3.00
|
-1.47
|
Mean Change from
Baseline in BASFIe
|
-2.26
|
-1.09
|
*Primary and ranked
secondary endpoints at Week 14. Not all ranked secondary endpoints
are shown. All primary and ranked secondary endpoints achieved
p-values of <0.0001 versus placebo.
|
a ASAS 40
is defined as a ≥40 percent improvement and an absolute improvement
of ≥2 units (on a scale of 0 to 10) from Baseline in at least 3 of
the 4 domains (patient's global assessment, back pain, function,
and inflammation) with no worsening at all in the remaining
domain.
|
b ASDAS Low Disease Activity is
defined as ASDAS score <2.1.
|
c SPARCC
scores for spine are calculated by adding up the dichotomous
outcomes from evaluations of the presence, depth, and intensity of
bone marrow edema lesions of the spine.
|
d Back
Pain is measured using 0 - 10 numerical rating scale (NRS) for
Total Back Pain (0 = no pain and 10 = severe pain).
|
e BASFI is a validated
patient-reported outcome (PRO) instrument for use in the AS patient
population. It consists of 10 items measured on a 0 to 10 NRS,
which assesses the ability to perform activities known to be
problematic to AS patients such as dressing, bending, reaching,
turning, and climbing steps. The total scores range from 0 to
10.
|
"Ankylosing spondylitis can have a profound impact on patients
and severely limit their ability to perform daily tasks," said
Filip Van den Bosch, SELECT-AXIS 2
investigator and professor in the Department of Rheumatology at the
University Hospital of Ghent University. "There is a great need for
effective treatment options for patients with an inadequate
response to biologic DMARDs. These encouraging study results
further demonstrate RINVOQ has the potential to impact the existing
treatment paradigm for patients with ankylosing spondylitis."
Safety data were consistent with SELECT-AXIS 1, previous Phase 3
studies in other indications, and the known safety profile of
RINVOQ, with no new risks identified.1-6 Through week
14, the most common adverse events (≥3 percent of patients)
for RINVOQ were COVID-19 and headache.1 The
proportion of patients with adverse events leading to
discontinuation, serious adverse events and serious infections were
0 percent/2.8 percent/2.4 percent for RINVOQ and 1.4 percent/0.5
percent/0 percent for placebo, respectively.1 Serious
infections included four events of COVID-19 and one of uveitis with
RINVOQ; two patients on RINVOQ developed non-serious, mild or
moderate herpes zoster limited to one dermatome.1 One
patient treated with placebo developed a malignancy (tonsil
cancer).1 No adjudicated major adverse cardiovascular
events, venous thromboembolic events or deaths were reported in
either group through week 14.1
Full results from the SELECT-AXIS-2 trial will be presented at a
future medical meeting and submitted for publication in a
peer-reviewed journal.
About SELECT-AXIS 2 – Study 11,7
SELECT-AXIS 2 was conducted as a master study protocol that
contains two standalone studies with randomization, data
collection, analysis and reporting conducted independently. The
Phase 3, randomized, placebo-controlled, double-blind studies are
evaluating the efficacy and safety of RINVOQ compared with placebo
on reduction of signs and symptoms in adult participants with
active axSpA including bDMARD-IR AS (Study 1) and nr-axSpA (Study
2). Study 1 enrolled 420 who were randomized to receive RINVOQ for
104 weeks or placebo for 14 weeks followed by RINVOQ for 90 weeks.
More information on this trial can be found
at www.clinicaltrials.gov (NCT04169373).
About Axial Spondyloarthritis
(axSpA)
Axial spondyloarthritis is a chronic
inflammatory disease that affects the spine, causing back pain,
limited mobility, and structural damage.8 It consists of
two subsets that have been clinically defined as ankylosing
spondylitis (AS) and non-radiographic axial spondyloarthritis
(nr-axSpA).8 In ankylosing spondylitis, patients have
definitive structural damage of the sacroiliac joints visible on
x-rays.8 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.8
About
RINVOQ® (upadacitinib)
Discovered
and developed by AbbVie scientists, RINVOQ is a selective and
reversible JAK inhibitor that is being studied in several
immune-mediated inflammatory diseases.1,6,7,9-15 In
human cellular assays, RINVOQ preferentially inhibits signaling by
JAK1 or JAK1/3 with functional selectivity over cytokine receptors
that signal via pairs of JAK2.6 RINVOQ is approved by
the European Commission for adults (15 mg and 30 mg) and
adolescents (15 mg) with moderate to severe atopic dermatitis.
RINVOQ 15 mg is approved by the European Commission for adults with
moderate to severe active rheumatoid arthritis, adults with active
psoriatic arthritis and adults with active ankylosing spondylitis.
RINVOQ 15 mg is also approved by the U.S. Food and Drug
Administration (FDA) for adults with moderately to severely active
rheumatoid arthritis. 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.9-15 Use of
RINVOQ in non-radiographic axial spondyloarthritis is not approved
and its safety and efficacy have not been established by regulatory
authorities.
EU Indications and Important Safety Information About
RINVOQ® (upadacitinib)6
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.
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, multi-dermatomal 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.
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. Globally, prescribing
information varies; refer to the individual country product label
for complete information.
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, 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 2020 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:
- AbbVie. Data on File: ABVRRTI73012
- Cohen S., et al. Safety profile of upadacitinib in rheumatoid
arthritis: integrated analysis from the SELECT phase III clinical
programme. Ann Rheum Dis. 2020 Oct 28;80(3):304-11.
- Mease, P.J., et al. Upadacitinib in Patients with Psoriatic
Arthritis and Inadequate Response to Biologics: 56-Week Data from
the Randomized Controlled Phase 3 SELECT-PsA 2 Study. Rheumatol
Ther. 2021 Apr 28. doi: 10.1007/s40744-021-00305-z. Online ahead of
print.
- Guttman-Yassky E., et al.
Once-daily upadacitinib versus placebo in adolescents and adults
with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure
Up 2): results from two replicate, double-blind, randomized
controlled phase 3 studies. Lancet.
doi:10.1016/s0140-6736(21)00588-2.
- Van der Heijde, D., et al.
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double-blind, placebo-controlled, phase 2/3 trial. Lancet. 2019
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GmbH & Co. KG; September 2021.
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https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
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- A Study to Compare Safety and Efficacy of Upadacitinib to
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https://clinicaltrials.gov/ct2/show/NCT03738397. Accessed on
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(U-ACCOMPLISH). ClinicalTrials.gov. 2021. Available at:
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- A Multicenter, Randomized, Double-Blind, Placebo-Controlled
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