- SEQUENCE, a Phase 3 head-to-head study,
compared risankizumab to ustekinumab for the treatment of
adult patients with moderately to severely active Crohn's disease
who have failed one or more anti-TNFs1
- Risankizumab met both primary endpoints of non-inferiority
for clinical remissiona (Crohn's Disease Activity Index
[CDAI]) at week 24 and superiority of endoscopic
remissionb at week 48 versus
ustekinumab1
- Risankizumab showed superiority versus ustekinumab for all
ranked secondary endpoints, including achievement of clinical
remissiona at week 48, achievement of endoscopic
responsec at week 48 and 24, achievement of steroid-free
endoscopic remissiond at week 48 and achievement of
steroid-free clinical remissione at week
481
- Safety results were consistent with the overall safety
profile of risankizumab, with no new safety risks
identified
NORTH
CHICAGO, Ill., Oct. 15,
2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
presented positive results from the head-to-head Phase 3 SEQUENCE
study that evaluated the efficacy and safety of risankizumab
(SKYRIZI®, 600 mg intravenous [IV] at week 0, 4 and 8
and 360 mg subcutaneous [SC] starting at week 12 and every 8 weeks
thereafter) compared to ustekinumab (STELARA®, IV dose
at week 0 and 90 mg SC every 8 weeks thereafter) in patients with
moderately to severely active Crohn's disease who have failed one
or more anti-TNFs.1 The data were presented at the
United European Gastroenterology (UEG) Week 2023, October 14-17.
"At AbbVie, we are committed to developing medicines and
generating evidence that advance care for people living with
immune-mediated conditions, including inflammatory bowel diseases,"
said Roopal Thakkar, M.D., senior
vice president, development and regulatory affairs and chief
medical officer, AbbVie. "Results such as these not only help
differentiate SKYRIZI as an option for managing Crohn's disease,
but also may help to evolve the field by further informing on
therapeutic strategies for patients."
The SEQUENCE study included two sequentially tested primary
endpoints:
- The results of the first primary endpoint, clinical remission
(CDAI <150) at week 24, met non-inferiority of risankizumab
versus ustekinumab (pre-defined non-inferiority margin of 10%);
remission rates were 59% in risankizumab group and 40% in
ustekinumab group.1 This endpoint was also analyzed post
hoc to test for superiority and achieved nominal
p<0.01.1
- The results of the second primary endpoint, endoscopic
remission (Simple Endoscopic Score for Crohn's disease [SES-CD] ≤4
and at least a 2-point reduction versus baseline and no sub-score
greater than 1 in any individual component) at week 48 demonstrated
superiority with risankizumab compared to ustekinumab with
remission rates of 32% in risankizumab group and 16% in ustekinumab
group (p<0.0001).1
Additionally, risankizumab demonstrated superiority
compared to ustekinumab for all ranked secondary endpoints,
including achievement of clinical remission at week 48, achievement
of endoscopic response at week 48 and 24, achievement of
steroid-free endoscopic remission at week 48, and achievement of
steroid-free clinical remission at week 48.1
SEQUENCE
Head-to-Head Study Results1*
|
|
Risankizumab
(n=255)
|
Ustekinumab
(n=265)
|
Primary
Endpoints
|
Clinical
Remissiona (Week 24; non-inferiority)
(Risankizumab,
n=128†)
(Ustekinumab,
n=137†)
|
59 %
|
40 %
|
Endoscopic
Remissionb (Week 48; superiority)
|
32 %
|
16 %
|
Secondary
Endpoints
(superiority)
|
Clinical
Remissiona (Week 48)
|
61 %
|
41 %
|
Endoscopic
Responsec (Week 48)
|
45 %
|
22 %
|
Endoscopic
Responsec (Week 24)
|
45 %
|
26 %
|
Steroid-free Endoscopic
Remissiond (Week 48)
|
31 %
|
15 %
|
Steroid-free Clinical
Remissione (Week 48)
|
61 %
|
40 %
|
*The first primary endpoint was clinical remission
(per CDAI) at week 24, and the second primary endpoint was
endoscopic remission (per SES-CD) at week 48. Non-inferiority was
met for the first primary endpoint. The second primary and all
secondary endpoints achieved statistical significance with a
p-value of <0.0001 vs ustekinumab.
†The first primary endpoint was tested when 50% of
participants completed the week 24 visit or ended the study
participation.
aClinical remission (per CDAI) was defined as CDAI
<150.
bEndoscopic remission (per SES-CD) was defined as SES-CD
≤4 with at least a 2-point reduction from baseline and no sub-score
greater than 1 in any individual component, as scored by central
reviewer.
cEndoscopic response (per SES-CD) was defined as a
decrease in SES-CD >50% from baseline (or for subjects with
isolated ileal disease and a baseline SES-CD of 4, at least a
2-point reduction from baseline), as scored by central
reviewer.
dSteroid-free endoscopic remission (per SES-CD) was
defined as the achievement of endoscopic remission without
receiving steroids at the corresponding visit.
eSteroid-free clinical remission (per CDAI) was defined
as the achievement of clinical remission without receiving steroids
at the corresponding visit.
"The results from the SEQUENCE study provide physicians with
important data to help inform therapy options that can help
patients reach treatment goals," said Laurent Peyrin-Biroulet,
M.D., Ph.D., director of the Infinity Institute, professor of
gastroenterology and head of the inflammatory bowel disease group,
gastroenterology department at the University Hospital of Nancy,
France. "These findings reaffirm
SKYRIZI as an efficacious interleukin-23 inhibitor
that can support the achievement of stringent targets that
contribute to improved care for patients."
The safety profile of risankizumab in the SEQUENCE study was
consistent with the known safety profile of risankizumab, with no
new safety risks observed.1 The most common adverse
events in risankizumab-treated patients were COVID-19, headache and
Crohn's disease. COVID-19, Crohn's disease and arthralgia were most
common among ustekinumab-treated patients.1 Serious
adverse events occurred in 10% of risankizumab-treated patients and
17% of ustekinumab-treated patients, respectively.1
Risankizumab is an IL-23 inhibitor approved for Crohn's disease,
psoriatic arthritis and psoriasis and is being evaluated as a
treatment for adults with moderate to severe ulcerative
colitis.1
Risankizumab (SKYRIZI) is part of a collaboration between
Boehringer Ingelheim and AbbVie, with AbbVie leading development
and commercialization globally.
About Crohn's Disease
Crohn's disease is a chronic, systemic disease that manifests as
inflammation within the gastrointestinal 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 the SEQUENCE Study1
The SEQUENCE study is a Phase 3, multicenter, randomized,
head-to-head (study drug open-label and efficacy assessment
blinded) to evaluate risankizumab versus ustekinumab for the
treatment of adults with moderate to severe Crohn's disease with a
history of one or more failed anti-tumor necrosis factor (TNF)
therapies (intolerance or inadequate response). All participants
had confirmed diagnosis for at least 3 months of moderate to severe
Crohn's disease assessed by CDAI score of 220 to 450 at baseline,
stool frequency, abdominal pain score and SES-CD.
In Part 1 that lasted 48 weeks, participants were randomized to
receive IV doses of 600 mg risankizumab at weeks 0, 4 and 8 and 360
mg SC maintenance doses at week 12 and every 8 weeks thereafter or
weight-based IV doses of ustekinumab as a single dose and 90 mg SC
doses every 8 weeks. In Part 2, participants who received
risankizumab in Part 1 and completed the 48-week visit continued to
receive SC risankizumab for up to an additional 220 weeks for
adverse event reporting. The primary endpoints were the percentage
of participants achieving clinical remission (CDAI <150) at week
24 and endoscopic remission (SES-CD ≤4, at least a 2-point
reduction versus baseline, and no sub score greater than 1 in any
individual variable) at week 48. Secondary endpoints include
percentage of participants achieving at week 48: clinical remission
(CDAI <150), steroid-free endoscopic remission, steroid-free
clinical remission, and at both 24 and 48 weeks endoscopic response
(decrease in SES-CD >50% from baseline or for participants with
isolated ileal disease and a baseline SES-CD of 4, at least a
2-point reduction from baseline). More information on this trial
can be found at
https://www.clinicaltrials.gov/ (NCT04524611).
About Risankizumab (SKYRIZI®)
SKYRIZI is an interleukin-23 (IL-23) inhibitor that selectively
blocks IL-23 by binding to its p19 subunit.4 IL-23, a
cytokine involved in inflammatory processes, is thought to be
linked to a number of chronic immune-mediated diseases.5
SKYRIZI is approved by the U.S. Food and Drug Administration (FDA)
and the European Medicines Agency for the treatment of plaque
psoriasis, psoriatic arthritis and Crohn's disease. The use of
risankizumab in ulcerative colitis is not approved and its safety
and efficacy have not been established by regulatory authorities.
Phase 3 trials of risankizumab in psoriasis, psoriatic arthritis,
Crohn's disease and ulcerative colitis are
ongoing.5-7
U.S. Indications and Important Safety Information about
SKYRIZI® (risankizumab-rzaa)8
SKYRIZI
is a prescription medicine used to treat adults with:
- moderate to severe plaque psoriasis who may benefit from taking
injections or pills (systemic therapy) or treatment using
ultraviolet or UV light (phototherapy).
- active psoriatic arthritis (PsA).
- moderate to severe Crohn's disease.
IMPORTANT SAFETY INFORMATION
What is the most important information I should know about
SKYRIZI® (risankizumab-rzaa)?
SKYRIZI is a prescription medicine that may cause serious
side effects, including:
Serious allergic reactions:
- Stop using SKYRIZI and get emergency medical help right away if
you get any of the following symptoms of a serious allergic
reaction:
- fainting, dizziness, feeling
lightheaded (low blood pressure)
- swelling of your face, eyelids, lips, mouth, tongue,
or throat
- trouble breathing or throat tightness
- chest tightness
- skin rash, hives
- itching
Infections:
SKYRIZI may lower the ability of your immune system to fight
infections and may increase your risk of infections. Your
healthcare provider should check you for infections and
tuberculosis (TB) before starting treatment with SKYRIZI and may
treat you for TB before you begin treatment with SKYRIZI if you
have a history of TB or have active TB. Your healthcare provider
should watch you closely for signs and symptoms of TB during and
after treatment with SKYRIZI.
- Tell your healthcare provider right away if you have an
infection or have symptoms of an infection, including:
– fever, sweats, or chills
– cough
– shortness of breath
– blood in your mucus (phlegm)
– muscle aches
– warm, red, or painful skin or sores on your body different
from your psoriasis
– weight loss
– diarrhea or stomach pain
– burning when you urinate or urinating more often than
normal
Do not use SKYRIZI if you are allergic to
risankizumab-rzaa or any of the ingredients in SKYRIZI. See the
Medication Guide or Consumer Brief Summary for a complete list of
ingredients.
Before using SKYRIZI, tell your healthcare provider about all
of your medical conditions,
including if you:
- have any of the conditions or symptoms listed in the
section "What is the most important information I should
know about SKYRIZI?"
- have an infection that does not go away or that keeps coming
back.
- have TB or have been in close contact with someone with
TB.
- have recently received or are scheduled to receive an
immunization (vaccine). Medicines that interact with the immune
system may increase your risk of getting an infection after
receiving live vaccines. You should avoid receiving live vaccines
right before, during, or right after treatment with SKYRIZI. Tell
your healthcare provider that you are taking SKYRIZI before
receiving a vaccine.
- are pregnant or plan to become pregnant. It is not known if
SKYRIZI can harm your unborn baby.
- are breastfeeding or plan to breastfeed. It is not known if
SKYRIZI passes into your breast milk.
- become pregnant while taking SKYRIZI. You are encouraged to
enroll in the Pregnancy Registry, which is used to collect
information about the health of you and your baby. Talk to your
healthcare provider or call 1-877-302-2161 to enroll in this
registry.
Tell your healthcare provider about all the medicines you
take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements.
What are the possible side effects of SKYRIZI?
SKYRIZI may cause serious side effects. See "What is the most
important information I should know about SKYRIZI?"
Liver problems in Crohn's disease: A person with Crohn's
disease who received SKYRIZI through a vein in the arm developed
changes in liver blood tests with a rash that led to
hospitalization. Your healthcare provider will do blood tests to
check your liver before, during, and up to 12 weeks of treatment
and may stop treatment with SKYRIZI if you develop liver problems.
Tell your healthcare provider right away if you notice any of the
following symptoms: unexplained rash, nausea, vomiting, stomach
(abdominal) pain, tiredness (fatigue), loss of appetite, yellowing
of the skin and eyes (jaundice), and dark urine.
The most common side effects of SKYRIZI in people treated for
Crohn's disease include: upper respiratory infections,
headache, joint pain, stomach (abdominal) pain, injection site
reactions, low red blood cells (anemia), fever, back pain, and
urinary tract infection.
The most common side effects of SKYRIZI in people treated for
plaque psoriasis and psoriatic arthritis include: upper
respiratory infections, headache, feeling tired, injection site
reactions, and fungal skin infections.
These are not all the possible side effects of SKYRIZI. Call
your doctor for medical advice about
side effects.
Use SKYRIZI exactly as your healthcare provider tells you to use
it.
SKYRIZI is available in a 150 mg/mL prefilled syringe and pen, a
600 mg/10 mL vial for intravenous infusion, and a 180 mg/1.2 mL or
360 mg/2.4 mL single-dose prefilled cartridge with on-body
injector.
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 Full Prescribing
Information and Medication
Guide for SKYRIZI.
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
and solutions 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, and eye care – and products and
services in our Allergan Aesthetics portfolio. For more information
about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on
X (formerly 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 and uses
of future or conditional verbs, 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 expressed or implied in the
forward-looking statements. Such risks and uncertainties include,
but are not limited to, challenges to intellectual property,
competition from other products, 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 2022 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, and specifically declines, 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: ABVRRTI76909
- Crohn's disease. Symptoms and Causes. Mayo Clinic. Available
at:
https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304.
- 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.
- SKYRIZI [Summary of Product Characteristics]. AbbVie Ltd.
Available at:
https://www.ema.europa.eu/en/documents/product-information/skyrizi-epar-product-information_en.pdf.
Accessed on August 21, 2023.
- Pipeline. AbbVie. Accessed March 3,
2023. https://www.abbvie.com/our-science/pipeline.html
- A study comparing risankizumab to placebo in participants with
active psoriatic arthritis including those who have a history of
inadequate response or intolerance to biologic therapy(ies)
(KEEPsAKE2). ClinicalTrials.gov. Updated February 28, 2023. Accessed March 3, 2023.
https://clinicaltrials.gov/ct2/show/NCT03671148
- A multicenter, randomized, double-blind, placebo
controlled induction study to evaluate the efficacy and safety of
risankizumab in participants with moderately to severely active
ulcerative colitis. ClinicalTrials.gov. Updated March 10, 2023. Accessed March 12, 2023.
https://clinicaltrials.gov/ct2/show/record/NCT03398148
- SKYRIZI [package insert]. North
Chicago, IL: AbbVie Inc.; 2022.
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