- Results of the M19-130 (SLEek) Phase 2 trial of upadacitinib
given alone or as a combination therapy (ABBV-599) met the primary
endpoint of systemic lupus erythematosus (SLE) Responder Index
(SRI-4) and steroid dose less than or equal to 10 mg prednisone
equivalent once per day at week 24 in patients with moderately to
severely active SLE1,2
- No new safety signals were identified with upadacitinib, and
a similar safety profile was observed for the combination therapy
(ABBV-599) as for treatment with upadacitinib
alone2,3,4,5,6,7
- SLE is a complex autoimmune disorder in which the body's
immune system attacks healthy tissue of the musculoskeletal system,
skin, kidneys, lungs and other critical organs, leading to symptoms
such as fatigue, joint pain and impaired
function.8,9
NORTH
CHICAGO, Ill., March 23,
2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced topline results from a Phase 2 study of upadacitinib
(RINVOQ®, 30 mg) given alone or as combination therapy
(ABBV-599) with a Bruton's Tyrosine Kinase inhibitor (elsubrutinib,
60 mg), once daily in patients with moderately to severely active
systemic lupus erythematosus (SLE).1 The
SLEek study met the primary endpoint of SLE Responder Index
(SRI-4) and steroid dose less than or equal to 10 mg prednisone
equivalent once per day at week 24 in the upadacitinib 30 mg
group.1,2 Based on the results, AbbVie is advancing
its clinical program of upadacitinib in SLE to Phase 3.
"Systemic lupus erythematosus is a very unpredictable life-long
condition and the way it affects a patient can change over time.
Therefore, there is a critical need for additional treatment
options," said Roopal Thakkar, M.D.,
senior vice president, development and regulatory affairs and chief
medical officer, AbbVie. "With a quarter-century of experience and
commitment to the treatment of rheumatic diseases, our focus
remains on areas of high unmet need like systemic lupus
erythematosus, and we look forward to further evaluation of the
potential benefits that upadacitinib could bring to patients."
A total of 341 participants enrolled in the Phase 2 study and
were subsequently divided into five experimental groups according
to treatment regimen (upadacitinib in combination with placebo;
upadacitinib, at two different doses, combined with elsubrutinib;
elsubrutinib in combination with placebo; placebo
only).1 The primary outcome measure was achievement of
the SRI-4 with a steroid dose less than or equal to 10 mg
prednisone equivalent once daily at week 24.1 SRI-4 is
defined as a greater or equal to 4-point reduction in SLE Disease
Activity Index 2000 score without worsening of the overall
condition or the development of significant disease activity in new
organ systems.1
The safety results for the upadacitinib 30 mg arm of the study
were generally consistent with the known safety profile of
upadacitinib, with no new safety signals identified.2-7
Types of adverse events reported with upadacitinib combined with
elsubrutinib were similar to those reported for patients treated
with upadacitinib alone.2 Full results from the study
will be presented at a future medical congress. Use of
upadacitinib and elsubrutinib in SLE are not approved and their
safety and efficacy have not been evaluated by regulatory
authorities.
Additional information about the study can be found at
www.clinicaltrials.gov under the identifier NCT03978520.
About Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a complex, multi-organ,
autoimmune disorder characterized by the production of pathogenic
autoantibodies and tissue deposition of immune
complexes.8,9 In SLE, the body's immune system attacks
healthy tissue of the musculoskeletal system, skin, kidneys, and
other critical organs, leading to symptoms such as fatigue, joint
pain and impaired function.8,9 The prevalence of SLE is
higher in women compared to men, and SLE occurs more frequently in
people of color.10,11
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.3-7,12,13,14,15,16,17,18,19 Based on enzymatic
and cellular assays, RINVOQ demonstrated greater inhibitory potency
for JAK-1 vs JAK-2, JAK-3 and TYK-2.3 The relevance of
inhibition of specific JAK enzymes to therapeutic effectiveness and
safety is not currently known.3
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.3-7,12-19 The use of upadacitinib in systemic
lupus erythematosus is not approved and its safety and efficacy
have not been evaluated by regulatory authorities.
US Indications and Important Safety Information about
RINVOQ® (upadacitinib)3
USES
RINVOQ is a prescription medicine used to treat:
- Adults with moderate to severe rheumatoid arthritis (RA)
when 1 or more medicines called tumor necrosis factor (TNF)
blockers have been used and did not work well or could not be
tolerated.
- Adults with active psoriatic arthritis (PsA) when 1 or
more medicines called TNF blockers have been used and did not work
well or could not be tolerated.
- Adults with moderate to severe ulcerative colitis (UC)
when 1 or more medicines called TNF blockers have been used and did
not work well or could not be tolerated.
- Adults with active ankylosing spondylitis (AS) when 1 or
more medicines called TNF blockers have been used and did not work
well or could not be tolerated.
- Adults with active non-radiographic axial spondyloarthritis
(nr-axSpA) with objective signs of inflammation when a TNF
blocker medicine has been used and did not work well or could not
be tolerated.
It is not known if RINVOQ is safe and effective in children with
juvenile idiopathic arthritis, psoriatic arthritis, ulcerative
colitis, ankylosing spondylitis, or non-radiographic axial
spondyloarthritis.
- Adults and children 12 years of age and older with moderate
to severe eczema (atopic dermatitis [AD]) that did not respond
to previous treatment and their eczema is not well controlled with
other pills or injections, including biologic medicines, or the use
of other pills or injections is not recommended.
RINVOQ is safe and effective in children 12 years of age and
older weighing at least 88 pounds (40 kg) with atopic
dermatitis.
It is not known if RINVOQ is safe and effective in children
under 12 years of age with atopic dermatitis.
IMPORTANT SAFETY INFORMATION
What is the most important information I should know about
RINVOQ?
RINVOQ may cause serious side effects, including:
- Serious infections. RINVOQ can lower your ability to
fight infections. Serious infections have happened while taking
RINVOQ, including tuberculosis (TB) and infections caused by
bacteria, fungi, or viruses that can spread throughout the body.
Some people have died from these infections. Your healthcare
provider (HCP) should test you for TB before starting RINVOQ and
check you closely for signs and symptoms of TB during treatment
with RINVOQ. You should not start taking RINVOQ if you have any
kind of infection unless your HCP tells you it is okay. If you get
a serious infection, your HCP may stop your treatment until your
infection is controlled. You may be at higher risk of developing
shingles (herpes zoster).
- Increased risk of death in people 50 years and older who
have at least 1 heart disease (cardiovascular) risk
factor.
- Cancer and immune system problems. RINVOQ may increase
your risk of certain cancers. Lymphoma and other cancers, including
skin cancers, can happen. Current or past smokers are at higher
risk of certain cancers, including lymphoma and lung cancer. Follow
your HCP's advice about having your skin checked for skin cancer
during treatment with RINVOQ. Limit the amount of time you spend in
sunlight. Wear protective clothing when you are in the sun and use
sunscreen.
- Increased risk of major cardiovascular (CV) events, such as
heart attack, stroke, or death, in people 50 years and older who
have at least 1 heart disease (CV) risk factor, especially if you
are a current or past smoker.
- Blood clots. Blood clots in the veins of the legs or
lungs and arteries can happen with RINVOQ. This may be
life-threatening and cause death. Blood clots in the veins of the
legs and lungs have happened more often in people who are 50 years
and older and with at least 1 heart disease (CV) risk factor.
- Allergic reactions. Symptoms such as rash (hives),
trouble breathing, feeling faint or dizzy, or swelling of your
lips, tongue, or throat, that may mean you are having an allergic
reaction have been seen in people taking RINVOQ. Some of these
reactions were serious. If any of these symptoms occur during
treatment with RINVOQ, stop taking RINVOQ and get emergency medical
help right away.
- Tears in the stomach or intestines and changes in certain
laboratory tests. Your HCP should do blood tests before you
start taking RINVOQ and while you take it. Your HCP may stop your
RINVOQ treatment for a period of time if needed because of changes
in these blood test results.
Do not take RINVOQ if:
- You are allergic to upadacitinib or any of the ingredients
in RINVOQ.
What should I tell my HCP BEFORE starting RINVOQ?
Tell your HCP if you:
- Are being treated for an infection, have an infection that
won't go away or keeps coming back, or have symptoms of an
infection, such as:
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Fever, sweating, or chills
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Shortness of breath
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Warm, red, or painful skin or sores on
your body
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Muscle aches
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Feeling tired
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Blood in phlegm
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Diarrhea or stomach pain
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Cough
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Weight loss
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Burning when urinating or urinating more
often than normal
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- Have TB or have been in close contact with someone with
TB.
- Are a current or past smoker.
- Have had a heart attack, other heart problems, or stroke.
- Have or have had any type of cancer, hepatitis B or C, shingles
(herpes zoster), blood clots in the veins of your legs or lungs,
diverticulitis (inflammation in parts of the large intestine), or
ulcers in your stomach or intestines.
- Have other medical conditions, including liver problems, low
blood cell counts, diabetes, chronic lung disease, HIV, or a weak
immune system.
- Live, have lived, or have traveled to parts of the country,
such as the Ohio and Mississippi
River valleys and the Southwest, that increase your risk of getting
certain kinds of fungal infections. If you are unsure if you've
been to these types of areas, ask your HCP.
- Have recently received or are scheduled to receive a vaccine.
People who take RINVOQ should not receive live vaccines.
- Are pregnant or plan to become pregnant. Based on animal
studies, RINVOQ may harm your unborn baby. Your HCP will check
whether or not you are pregnant before you start RINVOQ. You should
use effective birth control (contraception) to avoid becoming
pregnant during treatment with RINVOQ and for 4 weeks after your
last dose.
- Are breastfeeding or plan to breastfeed. RINVOQ may pass into
your breast milk. Do not breastfeed during treatment with RINVOQ
and for 6 days after your last dose.
Tell your HCP about all the medicines you take, including
prescription and over-the-counter medicines, vitamins, and herbal
supplements. RINVOQ and other medicines may affect each other,
causing side effects.
Especially tell your HCP if you take:
- Medicines for fungal or bacterial infections
- Rifampicin or phenytoin
- Medicines that affect your immune system
If you are not sure if you are taking any of these medicines,
ask your HCP or pharmacist.
What should I avoid while taking RINVOQ?
Avoid food or drink containing grapefruit during treatment with
RINVOQ as it may increase the risk of side effects.
What should I do or tell my HCP AFTER starting
RINVOQ?
- Tell your HCP right away if you have any symptoms of an
infection. RINVOQ can make you more likely to get infections or
make any infections you have worse.
- Get emergency help right away if you have any symptoms of a
heart attack or stroke while taking RINVOQ, including:
-
- Discomfort in the center of your chest that lasts for more than
a few minutes or that goes away and comes back
- Severe tightness, pain, pressure, or heaviness in your chest,
throat, neck, or jaw
- Pain or discomfort in your arms, back, neck, jaw, or
stomach
- Shortness of breath with or without chest discomfort
- Breaking out in a cold sweat
- Nausea or vomiting
- Feeling lightheaded
- Weakness in one part or on one side of your body
- Slurred speech
- Tell your HCP right away if you have any signs or symptoms of
blood clots during treatment with RINVOQ, including:
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Swelling
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Pain or tenderness in one or both
legs
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Sudden unexplained chest or upper back
pain
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Shortness of breath or difficulty
breathing
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- Tell your HCP right away if you have a fever or stomach-area
pain that does not go away, and a change in your bowel habits.
What are other possible side effects of RINVOQ?
Common side effects include upper respiratory tract infections
(common cold, sinus infections), shingles (herpes zoster), herpes
simplex virus infections (including cold sores), bronchitis,
nausea, cough, fever, acne, headache, increased blood levels of
creatine phosphokinase, allergic reactions, inflammation of hair
follicles, stomach-area (abdominal) pain, increased weight, flu,
tiredness, lower number of certain types of white blood cells
(neutropenia, lymphopenia), muscle pain, flu-like illness, rash,
increased blood cholesterol levels, and increased liver enzyme
levels.
A separation or tear to the lining of the back part of the eye
(retinal detachment) has happened in people with atopic dermatitis
treated with RINVOQ. Call your HCP right away if you have
any sudden changes in your vision during treatment with
RINVOQ.
These are not all the possible side effects of RINVOQ.
How should I take RINVOQ?
RINVOQ is taken once a day with or without food. Do not split,
crush, or chew the tablet. Take RINVOQ exactly as your HCP tells
you to use it. RINVOQ is available in 15 mg, 30 mg, and 45 mg
extended-release tablets.
This is the most important information to know about RINVOQ.
For more information, talk to your HCP.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit www.fda.gov/medwatch or call
1-800-FDA-1088.
If you are having difficulty paying for your medicine, AbbVie
may be able to help. Visit AbbVie.com/myAbbVieAssist to learn
more.
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. Anchored by a
longstanding commitment to discovering and delivering
transformative therapies, we pursue cutting-edge science that
improves our understanding of promising new pathways and targets,
ultimately helping more people living with rheumatic diseases reach
their treatment goals. For more information, visit AbbVie in
rheumatology.
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 our
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 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.
- A Study to Investigate the Safety and Efficacy of Elsubrutinib
and Upadacitinib Given Alone or in Combination in Participants With
Moderately to Severely Active Systemic Lupus Erythematosus (SLE)
(SLEek). ClinicalTrials.gov. 2022. Available at:
https://www.clinicaltrials.gov/ct2/show/NCT03978520?term=M19-130&draw=2&rank=2.
Accessed March 2023.
- AbbVie. Data on File: ABVRRTI75671
- Abbvie, Ltd. RINVOQ (upadacitinib) [highlights of prescribing
information]. Accessed March 20,
2023. https://www.rxabbvie.com/pdf/rinvoq_pi.pdf.
- Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction
and maintenance therapy for moderately to severely active
ulcerative colitis: results from three phase 3, multicentre,
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doi:10.1016/S0140-6736(22)00581-5.
- Mease PJ, Lertratanakul A, Anderson JK, et al. Upadacitinib for
psoriatic arthritis refractory to biologics: SELECT-PsA 2.
Annals of the Rheumatic Diseases. 2021;80(3):312-320.
doi:10.1136/annrheumdis-2020-218870.
- Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Once-daily
upadacitinib versus placebo in adolescents and adults with
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2): results from two replicate double-blind, randomised controlled
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doi:10.1016/S0140-6736(21)00588-2.
- Van der Heijde D, Song IH, Pangan AL, et al. Efficacy and
safety of upadacitinib in patients with active ankylosing
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double-blind, placebo-controlled, phase 2/3 trial. Lancet.
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- Catalina MD, Owen KA, Labonte AC, et al. The pathogenesis of
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10.1016/j.jaut.2019.102359. Epub 2019 Dec
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Accessed on August 26, 2022.
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GS, Winkelmayer WC, Costenbader KH. Epidemiology and
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- A Study of the Efficacy and Safety of Upadacitinib (ABT-494)
in Participants with Moderately to Severely Active Ulcerative
Colitis. clinicaltrials.gov; 2022. Available at:
https://clinicaltrials.gov/ct2/show/NCT03653026. Accessed
August 26, 2022.
- A Study to Evaluate the Safety and Efficacy of Upadacitinib
(ABT-494) for Induction and Maintenance Therapy in Participants
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- 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
August 26, 2022.
- A Study to Evaluate Efficacy and Safety of Upadacitinib in
Adult Participants with Axial Spondyloarthritis.
clinicaltrials.gov; 2021. Available at:
https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed
August 26, 2022.
- Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and
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inadequate response to conventional synthetic disease-modifying
anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind,
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- Cohen SB, van Vollenhoven RF, Winthrop KL, et al. Safety
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