NORTH CHICAGO, Ill.,
June 29, 2021 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced that upadacitinib (15 mg or 30 mg,
once daily) met the primary endpoint of clinical remission (per
Adapted Mayo Score) and all secondary endpoints at one-year (week
52) in the Phase 3 ulcerative colitis maintenance
study.1 Significantly more upadacitinib-treated patients
achieved clinical remission at week 52 compared to placebo (15 mg:
42 percent and 30 mg: 52 percent versus placebo: 12 percent;
p<0.001).1
"Ulcerative colitis is a disease with unpredictable symptoms and
frequent flares, which can make daily life challenging," said
Michael Severino, M.D., vice
chairman and president, AbbVie. "We are encouraged by these results
that demonstrate upadacitinib's potential as a treatment option for
patients with moderate to severe ulcerative colitis."
In this study, adults with moderate to severe ulcerative colitis
who achieved a clinical response (per partial Adapted Mayo Score)
following an 8-week study period of once-daily upadacitinib (45 mg)
induction treatment were re-randomized to receive upadacitinib 15
mg, upadacitinib 30 mg or placebo for an additional 52
weeks.1
All secondary endpoints were met, including the achievement of
endoscopic improvement, histologic-endoscopic mucosal improvement
(HEMI) and corticosteroid-free clinical remission at week
52.1 49 percent of patients treated with
upadacitinib 15 mg and 62 percent of patients treated with
upadacitinib 30 mg achieved endoscopic improvement at 52 weeks
versus 14 percent of patients in the placebo group
(p<0.001).1 In addition, 35 percent of patients
on upadacitinib 15 mg and 49 percent of patients on upadacitinib 30
mg achieved HEMI compared to 12 percent of patients in the placebo
group (p<0.001).1 Of patients who were in
remission at the completion of the 8-week induction studies,
corticosteroid-free remission was achieved in 57 percent of
patients in the upadacitinib 15 mg group and 68 percent of patients
in the upadacitinib 30 mg group compared to 22 percent of patients
in the placebo group (p<0.001).1
Phase 3
Maintenance Efficacy Results at Week
52*,1
|
|
Upadacitinib
15
mg, once daily (n=148)
|
Upadacitinib
30
mg, once daily (n=154)
|
Placebo (n=149)
|
Clinical
remissiona
|
42%
|
52%
|
12%
|
Endoscopic
improvementb
|
49%
|
62%
|
14%
|
HEMIc
|
35%
|
49%
|
12%
|
Corticosteroid-free
clinical remissiond
|
57%
|
68%
|
22%
|
*Primary endpoint was
clinical remission (per Adapted Mayo Score) at week 52. Not all
secondary endpoints are shown. All primary
and secondary endpoints achieved p-values of <0.001 versus
the placebo group.
a Clinical remission (per Adapted Mayo Score) is defined
as stool frequency subscore (SFS) ≤1 and not greater than baseline,
rectal
bleeding subscore (RBS) of 0 and endoscopic subscore ≤1.
b Endoscopic improvement is defined as endoscopic
subscore ≤1.
c HEMI is defined as an endoscopic subscore of ≤1
and Geboes score ≤3.1.
d Corticosteroid-free remission is defined as
clinical remission at week 52 and corticosteroid free for ≥90 days
prior to week 52
among patients with
clinical remission after 8 weeks of induction treatment. N=47, 58
and 54 for the upadacitinib 15 mg,
upadacitinib 30 mg
and placebo groups, respectively.
|
"Ulcerative colitis is a challenging disease to manage, and many
patients do not find relief from their most burdensome symptoms,"
said Remo Panaccione, M.D.,
professor of medicine and director of the IBD unit, University of Calgary. "These positive results
demonstrate upadacitinib's potential to achieve improvements in
clinical, endoscopic and histological outcomes at 52 weeks. This is
promising news for the IBD community."
A total of 746 patients who completed the 8-week upadacitinib
induction treatment with clinical response and received at least
one dose of the study drug in the maintenance period were included
in the safety analysis.1 The safety results of
upadacitinib (15 mg or 30 mg) were consistent with the safety
profile observed in the Phase 3 induction studies in ulcerative
colitis, as well as in previous studies across
indications.1-6 No new safety risks were
identified.1-6 The most common adverse events observed
in the upadacitinib groups during the 52-week study period were
nasopharyngitis, exacerbation of ulcerative colitis and blood
creatine phosphokinase increase.1 The exposure-adjusted
event rates of adverse events per 100 patient years were 16.0
events in the upadacitinib 15 mg group, 13.8 events in the
upadacitinib 30 mg group and 26.1 events in the placebo
group.1 The rates of infections were 6.2, 3.9 and 7.5
events per 100 patient years in the upadacitinib 15 mg,
upadacitinib 30 mg and placebo groups, respectively.1
The rates of adverse events leading to treatment discontinuation
per 100 patient years were 7.6 events and 7.9 events in patients
receiving upadacitinib 15 mg and upadacitinib 30 mg, respectively,
compared with 24.3 events in the placebo
group.1
Malignancies (excluding non-melanoma skin cancer) reported in
the study included one event in the upadacitinib 15 mg group, two
events in the upadacitinib 30 mg group and one event in the placebo
group.1 Adjudicated thrombotic events were reported
in the upadacitinib 15 mg group (two events of pulmonary embolism),
30 mg group (two events of deep vein thrombosis) and the placebo
group (one event of ovarian vein thrombosis).1 One
adjudicated major adverse cardiovascular event (MACE) was reported
in the upadacitinib 30 mg group and one was reported in the
placebo group.1 One patient in the placebo group
experienced events of adjudicated gastrointestinal
perforation.1 No deaths were reported.1
Full results from the Phase 3 maintenance study will be
presented at a future medical meeting and submitted for publication
in a peer-reviewed journal. Top-line results from the Phase 3
induction studies, U-ACHIEVE and U-ACCOMPLISH, were announced in
December 2020 and February 2021, respectively. Use of upadacitinib
in ulcerative colitis is not approved and its safety and efficacy
have not been evaluated by regulatory authorities.
About Ulcerative Colitis
Ulcerative colitis is a chronic, idiopathic, immune-mediated
inflammatory bowel disease (IBD) of the large intestine that causes
continuous mucosal inflammation extending, to a variable extent,
from the rectum to the more proximal colon.15,16 The
hallmark signs and symptoms of ulcerative colitis include
rectal bleeding, abdominal pain, bloody diarrhea, tenesmus (a sense
of pressure), urgency and fecal incontinence.15,17 The
disease course of ulcerative colitis varies between patients
and can range from quiescent disease to chronic refractory disease,
which in some cases can lead to surgery or complications, including
cancer or death.16,18 The severity of symptoms and
unpredictability of disease course can lead to substantial burden
and often disability among those living with the
disease.19
About the Phase 3 Maintenance Study1,9
The Phase 3 maintenance study is an ongoing, Phase 3
multicenter, randomized, double-blind, placebo-controlled study to
evaluate the efficacy and safety of upadacitinib in patients with
moderate to severe ulcerative colitis. Results from the induction
studies, U-ACHIEVE and U-ACCOMPLISH, were announced in December 2020 and February
2021, respectively. The objective of this maintenance study
is to evaluate the efficacy and safety of upadacitinib 15 mg and 30
mg, once daily, as a maintenance therapy compared to the placebo
group.
The primary endpoint was achievement of clinical remission (per
Adapted Mayo Score) at week 52. Secondary endpoints included
achievement of endoscopic improvement, HEMI and
corticosteroid-free clinical remission at one-year. More
information can be found
on www.clinicaltrials.gov (NCT02819635).
About the Upadacitinib Ulcerative Colitis
Program9,20,21
The global upadacitinib ulcerative colitis program evaluates
more than 1,300 patients with moderately to severely active
ulcerative colitis across three pivotal studies. These studies
include assessments of efficacy and safety of upadacitinib. Key
measures of efficacy include clinical remission (per Adapted Mayo
Score), clinical response (per Adapted Mayo Score), endoscopic
improvement and endoscopic response. More information on these
trials can be found
at www.clinicaltrials.gov (NCT02819635, NCT03653026,
NCT03006068).
About Upadacitinib (RINVOQ®)
Discovered and developed by AbbVie scientists, RINVOQ is a
selective and reversible JAK inhibitor that is being studied in
several immune-mediated inflammatory diseases.7-14 In
human cellular assays, RINVOQ preferentially inhibits signaling by
JAK1 or JAK1/3 with functional selectivity over cytokine receptors
that signal via pairs of JAK2.7 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. RINVOQ is
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 (DMARDs); 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; and for the treatment of active ankylosing spondylitis
(AS) in adult patients who have responded inadequately to
conventional therapy. The approved dose for RINVOQ is 15 mg. Phase
3 trials of RINVOQ in atopic dermatitis, axial spondyloarthritis,
Crohn's disease, ulcerative colitis, giant cell arteritis and
Takayasu arteritis are ongoing.9-14 Use of RINVOQ
in ulcerative colitis is not approved and its safety and efficacy
have not been evaluated by regulatory authorities.
Important Safety Information about RINVOQ®
(upadacitinib)7
RINVOQ U.S. Use and Important Safety
Information
RINVOQ is a prescription medicine used to treat
adults with moderate to severe rheumatoid arthritis in whom
methotrexate did not work well or could not be tolerated. It is not
known if RINVOQ is safe and effective in children under 18 years of
age.
What is the most important information I should know about
RINVOQ?
RINVOQ is a medicine that can lower the ability of
your immune system to fight infections. You should not start taking
RINVOQ if you have any kind of infection unless your healthcare
provider (HCP) tells you it is okay.
- Serious infections have happened in some people 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 HCP should
test you for TB before starting RINVOQ and check you closely for
signs and symptoms of TB during treatment with RINVOQ. You may be
at higher risk of developing shingles (herpes zoster).
- Lymphoma and other cancers, including skin cancers, can
happen in people taking RINVOQ.
- Blood clots in the veins of the legs or lungs and arteries
are possible in some people taking RINVOQ. This may be
life-threatening and cause death.
- Tears in the stomach or intestines and changes in certain
laboratory tests can happen. 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.
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.
- Have had any type of cancer, hepatitis B or C, shingles (herpes
zoster), or 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 that
increase your risk of getting certain kinds of fungal infections,
such as the Ohio and Mississippi
River valleys and the Southwest. If you are unsure if you've been
to these 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 while taking RINVOQ and for at least 4 weeks after your
last dose.
- Are breastfeeding or plan to breastfeed. RINVOQ may pass into
your breast milk. You should not breastfeed while taking RINVOQ and
for at least 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
Ask your HCP or pharmacist if you are not sure if you are taking
any of these medicines.
What should I 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.
- Have any signs or symptoms of blood clots during treatment with
RINVOQ, including:
-
- Swelling
- Sudden unexplained chest pain
- Pain or tenderness in the leg
- Shortness of breath
- Have a fever or stomach-area pain that does not go away, and a
change in your bowel habits.
What are the common side effects of RINVOQ?
These
include: upper respiratory tract infections (common cold, sinus
infections), nausea, cough, and fever. These are not all the
possible side effects of RINVOQ.
RINVOQ is taken once a day with or without food. Do not split,
break, crush, or chew the tablet. Take RINVOQ exactly as your HCP
tells you to use it.
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, 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 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: ABVRRTI72381.
- AbbVie. Data on File: ABVRRTI71710.
- AbbVie. Data on File: ABVRRTI71469.
- 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.
- RINVOQ® (upadacitinib) [Package Insert].
North Chicago, Ill.: AbbVie
Inc.
- Pipeline – Our Science | AbbVie. AbbVie. 2021. Available
at: https://www.abbvie.com/our-science/pipeline.html. Accessed
on June 13, 2021.
- 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. 2021.
Available at: https://clinicaltrials.gov/ct2/show/NCT02819635.
Accessed on June 13, 2021.
- A Study to Compare Safety and Efficacy of Upadacitinib to
Dupilumab in Adult Participants With Moderate to Severe Atopic
Dermatitis (Heads Up). ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT03738397. Accessed
on June 13, 2021.
- 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 June 13, 2021.
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled
Study of ABT-494 for the Induction of Symptomatic and Endoscopic
Remission in Subjects With Moderately to Severely Active Crohn's
Disease Who Have Inadequately Responded to or Are Intolerant to
Immunomodulators or Anti-TNF Therapy. ClinicalTrials.gov. 2021.
Available at: https://clinicaltrials.gov/ct2/show/NCT02365649.
Accessed on Accessed on June 13, 2021.
- 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 June 13, 2021.
- 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 June 13, 2021.
- Gajendran M., et al. A comprehensive review and update on
ulcerative colitis. Dis Mon. 2019 Dec;65(12):100851. doi:
10.1016/j.disamonth.2019.02.004. Epub 2019 Mar 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 June 13, 2021.
- Ulcerative colitis. Symptoms and Causes. Mayo Clinic. 2020.
Available at:
https://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/symptoms-causes/syc-20353326.
Accessed on June 13, 2021.
- Monstad, I., et al. Clinical course and prognosis in ulcerative
colitis: results from population-based and observational studies.
Ann Gastroenterol. 2014; 27(2): 95–104.
- Mehta F. Report: economic implications of inflammatory bowel
disease and its management. Am J Manag Care. 2016 Mar;22(3
Suppl):s51-60.
- A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in
Participants With Moderately to Severely Active Ulcerative Colitis
(U-ACCOMPLISH). ClinicalTrials.gov. 2021. Available
at: https://clinicaltrials.gov/ct2/show/NCT03653026. Accessed
on June 13, 2021.
- A Study to Evaluate the Long-Term Safety and Efficacy of
Upadacitinib (ABT-494) in Participants With Ulcerative Colitis
(UC). ClinicalTrials.gov. 2021. Available at:
https://clinicaltrials.gov/ct2/show/NCT03006068. Accessed on
June 13, 2021.
View original
content:https://www.prnewswire.com/news-releases/upadacitinib-rinvoq-met-the-primary-and-all-secondary-endpoints-in-the-52-week-phase-3-maintenance-study-in-ulcerative-colitis-patients-301321480.html
SOURCE AbbVie