- In patients with moderate to severe Crohn's disease who
achieved clinical response to upadacitinib induction
treatment, a significantly greater proportion treated with either
15 mg or 30 mg of upadacitinib achieved clinical
remission,a,b endoscopic responsec and
endoscopic remissiond at week 52 compared to
placebo
- The safety results in this study were generally consistent
with the known profile of upadacitinib, with no new safety risks
observed
- Upadacitinib, a JAK inhibitor discovered and developed by
AbbVie, is being studied as an oral therapy for moderate to severe
Crohn's disease and several other immune-mediated diseases
NORTH
CHICAGO, Ill., May 11, 2022
/PRNewswire/ -- AbbVie today announced positive topline results
from U-ENDURE, its Phase 3 maintenance study evaluating
upadacitinib in adult patients with moderate to severe Crohn's
disease who had an inadequate response or were intolerant to a
conventional or biologic therapy. The results showed that more
patients treated with either dose of upadacitinib (15 mg or 30 mg
once daily) achieved the co-primary endpoints of endoscopic
response and clinical remission, as well as the secondary endpoint
of endoscopic remission, at one year (week 52) compared to
placebo.1 Use of upadacitinib in Crohn's disease has not
been evaluated by health authorities. Results from the U-ENDURE
maintenance study, in addition to results from the U-EXCEED and
U-EXCEL induction studies, will be included in future regulatory
submissions.
In the U-ENDURE maintenance study, patients from U-EXCEED and
U-EXCEL who responded to 12 weeks of upadacitinib 45 mg oral
induction treatment were re-randomized to receive upadacitinib 15
mg, upadacitinib 30 mg, or placebo. Clinical remission was defined
by the Crohn's Disease Activity Index (CDAI) or by stool frequency
and abdominal pain score (SF/AP).
A significantly higher proportion of patients who received
upadacitinib 15 mg or 30 mg achieved clinical remission per the
CDAI at week 52: 37 and 48 percent, respectively, versus
15 percent in the placebo group
(p<0.0001).1 Results also showed that 36 and 46
percent of patients who received upadacitinib 15 mg and 30 mg,
respectively, achieved clinical remission at week 52 per SF/AP
compared to 14 percent in the placebo group
(p<0.0001).1 At week 52, 28 and 40 percent of
patients who received upadacitinib 15 mg and 30 mg, respectively,
achieved endoscopic response compared to 7 percent of patients who
received placebo (p<0.0001).1 In addition, 19
and 29 percent of patients who received upadacitinib 15 mg and 30
mg achieved endoscopic remission, respectively, compared to 5
percent of patients in the placebo group
(p<0.0001).1 A significantly higher proportion
of patients who received upadacitinib 15 mg or 30 mg achieved
corticosteroid-free clinical remission per CDAI and per SF/AP
compared to placebo at week 52 among patients taking
corticosteroids at baseline.1
"We are deeply committed to supporting Crohn's disease patients
who continue to live with challenging symptoms that impact their
daily lives," said Thomas Hudson,
M.D., senior vice president, research and development, chief
scientific officer, AbbVie. "These results represent important
progress as we work to bring new treatment options to patients with
inflammatory bowel disease."
"Symptomatic relief as well as healing of the intestinal mucosa
in Crohn's disease are important long-term treatment targets which
may be associated with slowing disease progression and better
quality of life for patients," said Julian
Panes, Emeritus Professor of Medicine and the Chief of the
IBD Unit at Hospital Clínic de Barcelona and lead study investigator.
"These results are encouraging and would be particularly important
for patients who have not found relief with other conventional or
biologic treatment options."
Efficacy Results at
Week 52ꝉ
|
|
Placebo
(n = 165)
|
Upadacitinib 15
mg
(n = 169)
|
Upadacitinib 30
mg
(n = 168)
|
Clinical
Remission
(per
CDAI)a
|
15%
|
37%*
|
48%*
|
Clinical
Remission
(per
SF/AP)b
|
14%
|
36%*
|
46%*
|
Endoscopic
Responsec
|
7%
|
28%*
|
40%*
|
Endoscopic
Remissiond
|
5%
|
19%*
|
29%*
|
Co-primary endpoints were clinical remission (per CDAI
for the U.S. FDA and per SF/AP for the EU EMA) and endoscopic
response at week 52.
ꝉ Efficacy was assessed
after the first 502 patients reached week 52.
* Statistically significant with p-values of
<0.0001 versus placebo.
|
a Clinical remission per CDAI is defined as CDAI
<150.
|
b
Clinical remission per SF/AP is
defined as average daily very soft or
liquid stool frequency ≤2.8 AND average daily abdominal pain score
≤1.0, and both not greater than baseline.
|
c Endoscopic response is defined as a decrease in
Simplified Endoscopic Score for Crohn's disease (SES-CD)
of >50 percent from baseline (or at least a 2-point
reduction from baseline for patients with a baseline SES-CD of 4),
as scored by central reviewer.
d
Endoscopic remission is defined as SES-CD
≤ 4 and at least a 2-point reduction from baseline and no subscore
> 1 in any individual variable, as scored by central
reviewer.
|
The safety results of upadacitinib (15 mg or 30 mg) were
generally consistent with the safety profile observed in the Phase
3 induction studies in Crohn's disease, as well as the known safety
profile of upadacitinib. No deaths were reported throughout the
study and no new safety risks were identified.
A total of 673 patients completed the 12-week upadacitinib
induction treatment with clinical response and received at least
one dose of the study drug in the placebo-controlled maintenance
period. The most common adverse events in the upadacitinib groups
were exacerbation of Crohn's disease, arthralgia and
pyrexia.1 Serious adverse event and serious
infection event rates per 100 patient years were the following for
placebo, upadacitinib 15 mg, and upadacitinib 30 mg groups,
respectively: 37.4/8.4, 25.0/6.1, 21.0/7.8. Malignancies (excluding
non-melanoma skin cancer [NMSC]) reported in the study included one
event in the upadacitinib 15 mg group, two events in the
upadacitinib 30 mg group and no events in the placebo
group.1 No adjudicated thrombotic events were
reported in the upadacitinib 15 mg and placebo groups; one
adjudicated hepatic vein thrombosis was reported in the
upadacitinib 30 mg group.1 No adjudicated major
adverse cardiovascular event (MACE) was reported in any treatment
group.1 One patient each in the upadacitinib 15 mg,
30 mg and placebo groups experienced an event of adjudicated
gastrointestinal perforation.1
The U-ENDURE Phase 3 study was designed to evaluate the efficacy
and safety of upadacitinib as maintenance therapy versus placebo in
patients with moderate to severe Crohn's disease who responded to
upadacitinib induction treatment in the U-EXCEED or
U-EXCEL induction studies. Full results from the U-ENDURE
study maintenance period will be presented at upcoming medical
conferences and published in a peer-reviewed medical journal. Use
of upadacitinib in Crohn's disease is not approved and its safety
and efficacy have not been evaluated by regulatory authorities.
About Crohn's Disease
Crohn's disease is a chronic, systemic disease that manifests as
inflammation within the gastrointestinal (or digestive) tract,
causing persistent diarrhea and abdominal pain.2,3 It is
a progressive disease, meaning it gets worse over time in a
substantial proportion of patients or may develop complications
that require urgent medical care including surgery.2,3
Because the signs and symptoms of Crohn's disease are
unpredictable, it causes a significant burden on people living with
the disease—not only physically, but also emotionally and
economically.2
About U-ENDURE
The U-ENDURE study is a Phase 3, multicenter, randomized,
double-blind, placebo-controlled maintenance and long-term study
designed to evaluate the efficacy and safety of upadacitinib 15 mg
and 30 mg in adults with moderate to severe Crohn's disease.
U-ENDURE enrolled patients who responded to 12 weeks of induction
treatment from the U-EXCEED and U-EXCEL studies. In addition to the
double-blind, placebo-controlled component, the U-ENDURE study also
included patients from the induction studies who either responded
to placebo or to extended treatment (an additional 12 weeks with 30
mg upadacitinib). During the study, patients who lost response were
eligible to receive 30 mg upadacitinib as rescue therapy.
The study included slightly different sets of primary and
secondary endpoints for the U.S. Food and Drug Administration
(FDA) and the EU European Medicines Agency (EMA). The primary
endpoints were achievement of clinical remission (per CDAI for the
U.S. FDA, and per SF/AP for the EU EMA, which was measured by
average daily very soft or liquid stool frequency and abdominal
pain score) and endoscopic response (per SES-CD) at week
52. More information can be found
on www.clinicaltrials.gov (NCT03345823).
About the Upadacitinib Phase 3 Crohn's Disease
Program4,5,6
The global upadacitinib Phase 3 program evaluates more than
1,000 patients with moderate to severe Crohn's disease across
two induction studies and a maintenance study. These studies
include assessments of efficacy, safety and tolerability of
upadacitinib. More information on these trials can be found at
www.clinicaltrials.gov (NCT03345836, NCT03345849,
NCT03345823).
About Upadacitinib (RINVOQ®)
Discovered and developed by AbbVie scientists, RINVOQ is a JAK
inhibitor that is being studied in several immune-mediated
inflammatory diseases.7-14 Based on
enzymatic and cellular assays, RINVOQ demonstrated greater
inhibitory potency for JAK1 vs JAK2, JAK3, and TYK2.14
The relevance of inhibition of specific JAK enzymes to therapeutic
effectiveness is not currently known.
Phase 3 trials of RINVOQ in rheumatoid arthritis, psoriatic
arthritis, axial spondyloarthritis, atopic dermatitis, ulcerative
colitis, giant cell arteritis, Takayasu arteritis and vitiligo are
ongoing.7-14 The use of
upadacitinib in Crohn's disease is not approved and its safety and
efficacy have not been evaluated by regulatory authorities.
RINVOQ® (upadacitinib) U.S. Use and
Important Safety Information14
RINVOQ is a prescription medicine used to treat:
- Adults with moderate to severe rheumatoid
arthritis when 1 or more tumor necrosis factor (TNF)
blockers have been used, and did not work well or could not be
tolerated.
- Adults with active psoriatic arthritis when 1 or
more tumor necrosis factor (TNF) blockers have been used, and did
not work well or could not be tolerated.
- Adults with moderate to severe ulcerative
colitis 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 when 1 or more
medicines called TNF blockers have 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, or ankylosing spondylitis.
- Adults and children 12 years of age and older with moderate
to severe eczema (atopic dermatitis) that did not respond
to previous treatment and whose eczema is not well controlled with
other pills or injections, including biologic medicines, or when
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.
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:
-
- Fever, sweating, or chills
- Shortness of breath
- Warm, red, or painful skin or sores on your body
- Muscle aches
- Feeling tired
- Blood in phlegm
- Diarrhea or stomach pain
- Cough
- Weight loss
- Burning when urinating or urinating more often than normal
- 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 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 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:
-
- Swelling
- Pain or tenderness in one or both legs
- Sudden unexplained chest or upper back pain
- Shortness of breath or difficulty breathing
- 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 the 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 http://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.
Please click here for the Full Prescribing
Information and Medication
Guide.
Globally, prescribing information varies; refer to the
individual country product label for complete information.
About AbbVie in Gastroenterology
With a robust clinical trial program, AbbVie is committed to
cutting-edge research to drive exciting developments in
inflammatory bowel diseases (IBD), like ulcerative colitis and
Crohn's disease. By innovating, learning and adapting, AbbVie
aspires to eliminate the burden of IBD and make a positive
long-term impact on the lives of people with IBD. For more
information on AbbVie in gastroenterology, visit
https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/gastroenterology.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, 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.
1 AbbVie.
Data on File: ABVRRTI73939
2 The Facts about Inflammatory Bowel Diseases. Crohn's
& Colitis Foundation of America. 2014. Available at:
https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf.
Accessed on January 11, 2022.
3 Crohn's disease. Symptoms and Causes. Mayo Clinic.
2022. Available at:
https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304.
Accessed on January 11, 2022.
4 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 Conventional and/or Biologic Therapies.
ClinicalTrials.gov. 2022. Available at:
https://clinicaltrials.gov/ct2/show/NCT03345849. Accessed
on January 11, 2022.
5 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. 2022. Available
at: https://clinicaltrials.gov/ct2/show/NCT03345836. Accessed
on January 11, 2022.
6 A Maintenance and Long-Term Extension Study of the
Efficacy and Safety of Upadacitinib (ABT-494) in Participants With
Crohn's Disease Who Completed the Studies M14-431 or M14-433.
ClinicalTrials.gov. 2022. Available at:
https://clinicaltrials.gov/ct2/show/NCT03345823. Accessed
on January 11, 2022.
7 Pipeline – Our Science | AbbVie. AbbVie. 2022.
Available at: https://www.abbvie.com/our-science/pipeline.html.
Accessed on January 11, 2022.
8 A Study to Evaluate Efficacy and Safety of
Upadacitinib in Adult Participants With Axial Spondyloarthritis
(SELECT AXIS 2). ClinicalTrials.gov. 2022. Available at:
https://clinicaltrials.gov/ct2/show/NCT04169373. Accessed
on January 11, 2022.
9 A Study to Evaluate the Safety and Efficacy of ABT-494
for Induction and Maintenance Therapy in Subjects With Moderately
to Severely Active Ulcerative Colitis. ClinicalTrials.gov. 2022.
Available at: https://clinicaltrials.gov/ct2/show/NCT02819635.
Accessed on January 11, 2022.
10 A Study to Compare Safety and Efficacy of
Upadacitinib to Dupilumab in Adult Participants With Moderate to
Severe Atopic Dermatitis (Heads Up). ClinicalTrials.gov. 2022.
Available at: https://clinicaltrials.gov/ct2/show/NCT03738397.
Accessed on January 11, 2022.
11 A Study of the Efficacy and Safety of Upadacitinib
(ABT-494) in Participants With Moderately to Severely Active
Ulcerative Colitis (U-ACCOMPLISH). ClinicalTrials.gov. 2022.
Available at: https://clinicaltrials.gov/ct2/show/NCT03653026.
Accessed on January 11, 2022.
12 A Study to Evaluate the Safety and Efficacy of
Upadacitinib in Participants With Giant Cell Arteritis
(SELECT-GCA). ClinicalTrials.gov. 2022. Available at:
https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed
on January 11, 2022.
13 A Study to Evaluate the Efficacy and Safety of
Upadacitinib in Subjects With Takayasu Arteritis (TAK)
(SELECT-TAK). ClinicalTrials.gov. 2022. Available at:
https://clinicaltrials.gov/ct2/show/NCT04161898. Accessed
on January 11, 2022.
14 RINVOQ® (upadacitinib) [Package
Insert]. North Chicago, Ill.: AbbVie Inc.
|
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