NORTH CHICAGO, Ill.,
June 6, 2020 /PRNewswire/
-- AbbVie (NYSE: ABBV), a research-based global
biopharmaceutical company, today announced new Phase 3 data from
the SELECT-CHOICE clinical trial, showing that RINVOQ™
(upadacitinib, 15 mg, once daily) met the primary endpoint of
non-inferiority versus ORENCIA® (abatacept) on change
from baseline in Disease Activity Score 28 C-Reactive Protein
(DAS28-CRP) at week 12.1 In addition, RINVOQ met the key
secondary endpoints of superiority versus ORENCIA on change
from baseline in DAS28-CRP at week 12 and proportion of patients
achieving clinical remission at week 12 as measured by
DAS28-CRP<2.6.1 The study evaluated RINVOQ in adult
patients with moderate to severe active rheumatoid arthritis and
prior inadequate response or intolerance to biologic
disease-modifying anti-rheumatic drugs (DMARDs). Full results were
presented today at the 2020 Annual European E-Congress of
Rheumatology (EULAR).
SELECT-CHOICE is the sixth and final Phase 3 study from the
robust SELECT rheumatoid arthritis clinical trial
program.1,2 RINVOQ, a selective and reversible JAK
inhibitor discovered and developed by AbbVie, is approved 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 DMARDs.2
"Despite tremendous progress in the treatment of rheumatoid
arthritis, about 70 percent of patients are still not achieving
clinical remission with established therapies," said
Michael Severino, M.D., vice
chairman and president, AbbVie. "We are pleased with the results as
they add to our growing body of evidence that RINVOQ may offer more
adult patients with rheumatoid arthritis a better chance at
achieving clinical remission, including those who have already
failed a prior biologic."
"These data show that upadacitinib was superior to abatacept
with regard to the proportion of patients achieving remission,"
said Professor Andrea Rubbert-Roth,
M.D., deputy director, Division of Rheumatology, Cantonal Hospital
St. Gallen, Switzerland.
"SELECT-CHOICE represents the first head-to-head study in
rheumatoid arthritis patients who have failed biologic DMARDs and
compares upadacitinib to a different biologic DMARD. Studies like
this are important for daily decision-making in practice."
In this study, RINVOQ met both the primary (non-inferiority) and
secondary (superiority) endpoints, with a change from baseline in
DAS28-CRP at week 12 of -2.52 compared to -2.00 in patients treated
with ORENCIA.1 In addition, 30 percent of patients
receiving RINVOQ achieved clinical remission at week 12
(DAS28-CRP<2.6) compared to 13 percent of patients receiving
ORENCIA (p<0.001).1
ACR20/50/70 responses were also higher in the RINVOQ group
compared to the ORENCIA group (76/46/22 percent versus 66/34/14
percent, respectively, nominal p<0.05) at week 12.1
Improvements in disease activity and remission rates were
maintained through 24 weeks.1
SELECT-CHOICE
Efficacy Results1,†
|
|
Week 12
|
Week 24
|
|
RINVOQ 15
mg
(n=303)
|
ORENCIA
(n=309)
|
RINVOQ 15
mg
(n=303)
|
ORENCIA
(n=309)
|
Δ DAS28-CRP, (Δ 95%
CI)
|
-2.52***###
(-2.66,
-2.37)
|
-2.00
(-2.14,
-1.85)
|
-2.91***
(-3.06,-2.76)
|
-2.57
(-2.72,-2.42)
|
Clinical
Remission
(DAS28-CRP)a
|
30%***###
|
13.3%
|
45.9%***
|
31.4%
|
ACR20b,‡
|
75.6%*
|
66.3%
|
78.9%
|
73.8%
|
ACR50b,‡
|
46.2%**
|
34.3%
|
59.4%*
|
49.5%
|
ACR70b,‡
|
21.5%**
|
13.6%
|
37.3%**
|
26.5%
|
|
† Primary
endpoint was non-inferiority versus ORENCIA as measured by change
from baseline in DAS28-CRP at week 12 against a margin of 0.6.
Ranked secondary endpoints were superiority as measured by change
from baseline in DAS28-CRP versus ORENCIA and proportion of
patients achieving clinical remission, as measured by
DAS28-CRP<2.6 at week 12. Not all additional endpoints
shown.
|
*, **, *** p≤0.05,
0.01 and 0.001, respectively for RINVOQ vs. ORENCIA.
|
###
p<0.001 for RINVOQ vs. ORENCIA,
non-inferiority/superiority.
|
‡ ACR20/50/70 were prespecified,
unranked endpoints, P values are nominal. ACR20 response was not
statistically significant between RINVOQ and ORENCIA at 24
weeks.
|
a Clinical
remission is defined as Disease Activity Score with 28 joint counts
(C-reactive protein) (DAS28-CRP) less than 2.6.
|
b
ACR20/50/70 is defined as at least a 20 percent/50 percent/70
percent reduction from baseline in the number of both tender and
swollen joint counts and equivalent improvement in three or more of
the five remaining American College of Rheumatology core set
measures: patient assessments of pain, global disease activity,
physical function, physician global assessment of disease activity
and acute phase reactant.
|
The safety profile of RINVOQ (15 mg) was consistent with that
observed in previously reported studies in rheumatoid
arthritis, with no new safety risks detected.1 Through
week 24, serious adverse events occurred in 3.3 percent of patients
in the RINVOQ group, compared to 1.6 percent of patients in the
ORENCIA group.1 There were three cases of
serious infection reported in the RINVOQ group and one in the
ORENCIA group.1 There were also 23 cases of hepatic
disorder (primarily liver enzyme elevations) in the RINVOQ group
compared to five cases of hepatic disorder in the
ORENCIA group.1 All hepatic disorder events were
non-serious.3 Most of the events were transient ALT/AST
elevations and considered mild to moderate in severity.3
None led to study drug interruption.3 Four cases of
herpes zoster were reported in the RINVOQ group and four cases in
the ORENCIA group.1 Across both groups,
there were no malignancies reported.1 One major adverse
cardiovascular event (MACE) and two adjudicated cases of venous
thromboembolic events (VTE) were reported in the RINVOQ group, and
both patients had at least one risk factor for VTE.1
There were no MACE and VTE reported in the ORENCIA
group.1 There were two deaths in the RINVOQ group, one
of which was non-treatment emergent, as well as one non-treatment
emergent death in the ORENCIA group.1
About SELECT-CHOICE1
SELECT-CHOICE is a Phase 3, multicenter, randomized,
double-blind, active-controlled study designed to evaluate the
safety and efficacy of RINVOQ in combination with conventional
synthetic disease-modifying anti-rheumatic drugs (csDMARDs)
compared to ORENCIA (abatacept) in combination with csDMARDs
in adult patients with moderate to severe active rheumatoid
arthritis who have an inadequate response to or intolerance to
biologic DMARDs. Patients were randomized to once daily RINVOQ (15
mg) or intravenous ORENCIA (at day 1, weeks 2, 4, 8, 12, 16
and 20 [<60 kg: 500 mg; 60-100 kg: 750 mg; >100 kg: 1,000
mg]), with all patients continuing background stable csDMARDs.
The primary endpoint was change from baseline in DAS28-CRP at
week 12 showing non-inferiority in patients receiving RINVOQ
(15 mg) compared to those receiving ORENCIA. Ranked secondary
endpoints included superiority to ORENCIA in terms of change from
baseline in DAS28-CRP at week 12 and proportion of patients
achieving clinical remission, as defined by DAS28-CRP<2.6 at
week 12. More information on this trial can be found at
www.clinicaltrials.gov (NCT03086343).
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, 2,
4-12 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, psoriatic arthritis, axial
spondyloarthritis, Crohn's disease, atopic dermatitis, ulcerative
colitis and giant cell arteritis are ongoing.1,
4-12
Important EU Safety Information about RINVOQ™
(upadacitinib)2
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 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, competition from
other products, challenges to intellectual property, 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. 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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- Efficacy and Safety of Upadacitinib Versus Abatacept in
Patients With Active Rheumatoid Arthritis and Prior Inadequate
Response or Intolerance to Biologic Disease-modifying
Anti-rheumatic Drugs (SELECT-CHOICE): A Double-Blind, Randomized
Controlled Phase 3 Trial. 2020 EULAR E-Congress; SAT0151.
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland
GmbH & Co. KG; March 2020.
Available at:
https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
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at: https://www.abbvie.com/our-science/pipeline.html. Accessed
on May 18, 2020.
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Adalimumab in Participants With Psoriatic Arthritis Who Have an
Inadequate Response to at Least One Non-Biologic Disease Modifying
Anti-Rheumatic Drug (SELECT - PsA 1). ClinicalTrials.gov. 2020.
Available at: https://clinicaltrials.gov/ct2/show/NCT03104400.
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Remission in Subjects With Moderately to Severely Active Crohn's
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ClinicalTrials.gov. 2020. Available
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Participants With Active Psoriatic Arthritis Who Have a History of
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