NORTH CHICAGO, Ill.,
Jan. 7, 2021 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced positive results from two Phase 3
induction studies, ADVANCE and MOTIVATE, showing both doses of
risankizumab (600 mg and 1200 mg) met both primary endpoints of
clinical remission and endoscopic response at week 12 in adult
patients with moderate to severe Crohn's disease.1,2 The
ADVANCE study enrolled patients who had an inadequate response or
were intolerant to conventional and/or biologic
therapy.1 The MOTIVATE study evaluated patients who had
responded inadequately or were intolerant to biologic
therapy.2
"The progressive nature of Crohn's disease makes it critical
that treatment options go beyond symptoms to help patients achieve
endoscopic response," said Michael Severino, M.D., vice
chairman and president, AbbVie. "Despite the availability of
current treatments, many patients still do not achieve disease
control. These positive results show how targeting IL-23 can
rapidly induce improvements for people living with this condition.
We look forward to advancing research showing risankizumab's
potential to improve clinical and endoscopic outcomes and minimize
the burden of Crohn's disease for patients."
In both studies, clinical remission was measured by CDAI
(Crohn's Disease Activity Index) and PRO-2 (two-component
patient-reported outcome).1,2 In the ADVANCE study, a
significantly greater proportion of patients treated with
risankizumab 600 mg or 1200 mg achieved clinical remission per CDAI
at week 12 (45 and 42 percent of patients, respectively, compared
to 25 percent of patients receiving placebo;
p<0.001).1 Similar results were seen with clinical
remission per PRO-2 (43 and 41 percent, respectively, compared
to 21 percent of patients receiving placebo;
p<0.001).1 A significantly greater proportion of
patients treated with either dose of risankizumab achieved
endoscopic response at week 12 (40 and 32 percent of patients
receiving risankizumab 600 mg or 1200 mg, respectively, versus
12 percent in the placebo group; p<0.001).1
In the MOTIVATE study, 42 and 41 percent of patients treated
with risankizumab 600 mg or 1200 mg achieved clinical remission
(per CDAI) at week 12, respectively, versus 19 percent of patients
receiving placebo (p<0.001).2 A significantly greater
proportion of patients in MOTIVATE also achieved clinical remission
(per PRO-2) (35 and 39 percent of risankizumab 600 mg or 1200
mg-treated patients, respectively, compared to 19 percent of
patients receiving placebo; p=0.001 for 600 mg; p<0.001 for 1200
mg).2 In addition, 29 and 34 percent of patients
receiving risankizumab 600 mg or 1200 mg achieved endoscopic
response, respectively, versus 11 percent in the placebo group
(p<0.001).2
Additionally, multiplicity-adjusted key secondary endpoints
showed significant clinical and endoscopic outcomes, with
symptom improvement observed as early as week 4.1,2
After 4 weeks of treatment in both studies, a greater proportion of
patients receiving either dose of risankizumab achieved clinical
response (per CDAI) compared to placebo.1,2
Specifically, in ADVANCE, 41 and 37 percent of patients receiving
risankizumab 600 mg or 1200 mg achieved clinical response (per
CDAI) compared to 25 percent in the placebo group (p<0.001 for
600 mg; p=0.008 for 1200 mg).1 In MOTIVATE, 36 and 33
percent of patients receiving risankizumab 600 mg or 1200 mg
achieved clinical response (per CDAI), respectively, compared to 21
percent in the placebo group (p=0.002 for 600 mg; p=0.012 for 1200
mg).2
"Helping patients achieve both clinical remission and endoscopic
response early is paramount when treating Crohn's disease," said
Remo Panaccione, M.D., professor of
medicine and director of the IBD unit, University of Calgary. "It was exciting to see that
a significant proportion of patients treated with risankizumab
achieved both measures after 12 weeks of treatment, as well as
achieving symptom improvement at week 4. These data are
encouraging as we continue to evaluate the potential of
risankizumab in Crohn's disease."
Efficacy Results
at Week 12*
|
|
ADVANCE1
|
MOTIVATE2
|
|
Risankizumab
600 mg
(n=336)
|
Risankizumab
1200 mg
(n=339)
|
Placebo
(n=175)
|
Risankizumab
600 mg
(n=191)
|
Risankizumab
1200 mg
(n=191)
|
Placebo
(n=187)
|
Clinical
Remission
(per CDAI)a
|
45%
|
42%
|
25%
|
42%
|
41%
|
19%
|
Clinical
Remission
(per PRO-2)b
|
43%
|
41%
|
21%
|
35%
|
39%
|
19%
|
Endoscopic
Responsec
|
40%
|
32%
|
12%
|
29%
|
34%
|
11%
|
|
* In both studies,
the primary endpoints were clinical remission (per CDAI for the
U.S. protocol and per PRO-2 for the outside of the U.S. [OUS]
protocol) and endoscopic response (for both protocols) at week 12.
All endpoints shown for both studies achieved p-values of
≤0.001.
|
a Clinical
remission (per CDAI) is defined as a CDAI score of
<150.
|
b Clinical remission (per
PRO-2) is based on average daily stool frequency and average daily
abdominal pain score.
|
c
Endoscopic response is defined as a decrease in simple endoscopic
score for Crohn's disease (SES-CD) of >50 percent from
baseline (or ≥50 percent from baseline for subjects with
isolated ileal disease and a baseline SES-CD of 4), as scored by
central reviewer.
|
During the 12-week induction period, the safety profile of
risankizumab in both studies was generally consistent with the
known safety profile of risankizumab.1-6 No new safety
risks were observed.1-6
In ADVANCE, serious adverse events (SAEs) occurred in 7.2
percent of patients in the risankizumab 600 mg group and 3.8
percent of patients in the risankizumab 1200 mg group compared to
15.1 percent of patients in the placebo group.1 The most
common adverse events (AEs) observed in the risankizumab treatment
groups were headache, nasopharyngitis and fatigue.1
Rates of serious infections were 0.8 and 0.5 percent in those
treated with risankizumab 600 mg or 1200 mg, respectively, and 3.8
percent in patients who received placebo.1 The rates of
AEs leading to discontinuation of the study drug were 2.4 and 1.9
percent of patients treated with risankizumab 600 mg or 1200 mg,
respectively, compared with 7.5 percent on placebo.1 In
ADVANCE, there were two deaths reported in the placebo
group.1 There were no adjudicated major adverse cardiac
events (MACE) or adjudicated anaphylactic reaction events
reported.1
In MOTIVATE, SAEs occurred in 4.9 percent of patients in the
risankizumab 600 mg group and 4.4 percent of patients in the
risankizumab 1200 mg group compared to 12.6 percent of patients in
the placebo group.2 The most common AEs observed in the
risankizumab treatment groups were headache, arthralgia and
nasopharyngitis.2 Rates of serious infections were 0.5
and 1.0 percent in those treated with risankizumab 600 mg or 1200
mg, respectively, and 2.4 percent in patients who received
placebo.2 The rates of AEs leading to discontinuation of
the study drug were 1.0 and 2.4 percent of patients treated with
risankizumab 600 mg or 1200 mg, respectively, compared with 8.2
percent on placebo.2 There was one death in the
risankizumab 1200 mg group due to squamous cell carcinoma of the
lung diagnosed on study day 8, which was assessed as unrelated to
the study drug by the investigator.2 There were no
adjudicated MACE or adjudicated anaphylactic reaction events
reported.2
Full results from the ADVANCE and MOTIVATE studies will be
presented at upcoming medical conferences and published in a
peer-reviewed medical journal. Use of risankizumab in Crohn's
disease is not approved and its safety and efficacy have not been
evaluated by regulatory authorities. The maintenance study for
Crohn's disease is ongoing and once completed will be submitted to
regulatory authorities with the induction studies.
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 (or digestive) tract,
causing persistent diarrhea, abdominal pain and rectal
bleeding.9-11 It is a progressive disease, meaning it
gets worse over time.10,11 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.12
About the ADVANCE and MOTIVATE
Studies1,2,13,14
The ADVANCE and MOTIVATE studies are Phase 3, multicenter,
randomized, double-blind, placebo-controlled induction studies
designed to evaluate the efficacy and safety of risankizumab in
adults with moderate to severe Crohn's disease. The objective of
the two Phase 3 induction studies is to evaluate the efficacy and
safety of two doses of risankizumab, 600 mg and 1200 mg, compared
to placebo. The ADVANCE study included a mixed population of
patients who had responded inadequately or are intolerant to
conventional and/or biologic therapy. The MOTIVATE study evaluated
patients who had responded inadequately or were intolerant to
biologic therapy.
Both studies included slightly different sets of primary and
secondary endpoints for U.S. protocol and OUS protocol. The primary
endpoints were achievement of clinical remission (per CDAI for the
U.S. protocol, which was measured by a CDAI score less than 150,
and per PRO-2 for the OUS protocol, which was measured by daily
stool frequency and abdominal pain score) and endoscopic response
(for both protocols) at week 12. Endoscopic response is defined as
a decrease in SES-CD of greater than 50 percent from baseline
(or at least a greater than or equal to 50 percent decrease from
baseline in patients with isolated ileal disease and a baseline
SES-CD of 4), as scored by a central reviewer.
Multiplicity-adjusted key secondary endpoints included clinical
response (per CDAI) at week 4 defined as a decrease in CDAI score
from baseline of ≥100 points (CDAI100). More information can be
found on www.clinicaltrials.gov (ADVANCE: NCT03105128;
MOTIVATE: NCT03104413).
About risankizumab (SKYRIZI®)
SKYRIZI is an interleukin-23 (IL-23) inhibitor that selectively
blocks IL-23 by binding to its p19 subunit.15,16 IL-23,
a cytokine involved in inflammatory processes, is thought to be
linked to a number of chronic immune-mediated diseases, including
Crohn's disease.15,16 In April
2019, SKYRIZI received U.S. Food and Drug Administration
approval for the treatment of moderate to severe plaque psoriasis
in adults who are candidates for systemic therapy or phototherapy.
The approved dose for SKYRIZI is 150 mg (two 75 mg injections),
administered by subcutaneous injection at week 0 and 4, and every
12 weeks thereafter. SKYRIZI was also approved by the European
Commission in April 2019. Phase 3
trials of SKYRIZI in psoriasis, Crohn's disease and psoriatic
arthritis are ongoing.7,8,13,14 Use of SKYRIZI in
Crohn's disease is not approved and its safety and efficacy have
not been evaluated by regulatory authorities.
About SKYRIZI® (risankizumab-rzaa) in the
United States16
SKYRIZI is indicated for the treatment of moderate to severe
plaque psoriasis in adults who are candidates for systemic therapy
or phototherapy.
Important Safety Information16
Infection
SKYRIZI may increase the risk of infection. Do not initiate
treatment with SKYRIZI in patients with a clinically important
active infection until it resolves or is adequately treated.
In patients with a chronic infection or a history of recurrent
infection, consider the risks and benefits prior to prescribing
SKYRIZI. Instruct patients to seek medical advice if signs or
symptoms of clinically important infection occur. If a patient
develops such an infection or is not responding to standard
therapy, closely monitor and discontinue SKYRIZI until the
infection resolves.
Pre-Treatment Evaluation for Tuberculosis (TB)
Prior to initiating treatment with SKYRIZI, evaluate for TB
infection and consider treatment in patients with latent or active
TB for whom an adequate course of treatment cannot be confirmed.
Monitor patients for signs and symptoms of active TB during and
after SKYRIZI treatment. Do not administer SKYRIZI to patients with
active TB.
Immunizations
Prior to initiating SKYRIZI, consider completion of all age
appropriate immunizations according to current immunization
guidelines. Avoid use of live vaccines in patients treated with
SKYRIZI.
Adverse Reactions
Most common (≥1%) adverse reactions associated with SKYRIZI
include upper respiratory infections, headache, fatigue, injection
site reactions, and tinea infections.
This is not a complete summary of all safety
information.
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
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 2019 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: ABVRRTI71474.
- AbbVie. Data on File: ABBVRRI71526.
- Gordon K., et al. Efficacy and safety of risankizumab in
moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2):
results from two double-blind, randomised, placebo-controlled and
ustekinumab-controlled phase 3 trials. The Lancet. 2018 Aug
25;392(10148):650-661.
- Reich, K., et al. Risankizumab compared with adalimumab in
patients with moderate-to-severe plaque psoriasis (IMMvent): a
randomised, double-blind, active-comparator-controlled phase 3
trial. Lancet. 2019 Aug 17;394(10198):576-586. doi:
10.1016/S0140-6736(19)30952-3.
- Blauvelt, A., et al. Efficacy and Safety of Continuous Q12W
Risankizumab Versus Treatment Withdrawal: 2-Year Double-Blinded
Results from the Phase 3 IMMhance Trial. Poster #478. 24th World
Congress of Dermatology. 2019.
- Feagan, B., et al. Induction therapy with the selective
interleukin-23 inhibitor risankizumab in patients with
moderate-to-severe Crohn's disease: a randomised, double-blind,
placebo-controlled phase 2 study. Lancet. 2017 Apr
29;389(10080):1699-1709. doi: 10.1016/S0140-6736(17)30570-6. Epub
2017 Apr 12.
- A Study to Assess the Safety and Efficacy of Risankizumab for
Maintenance in Moderate to Severe Plaque Type Psoriasis
(LIMMITLESS). ClinicalTrials.gov. 2020. Available at:
https://clinicaltrials.gov/ct2/show/NCT03047395. Accessed on
December 18, 2020.
- 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. 2020. Available at:
https://clinicaltrials.gov/ct2/show/NCT03671148. Accessed on
December 18, 2020.
- Kaplan, G. The global burden of IBD: from 2015 to 2025. Nat Rev
Gastroenterol Hepatol. 2015 Dec;12(12):720-7. doi:
10.1038/nrgastro.2015.150.
- 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 December 18, 2020.
- Crohn's disease. Symptoms and Causes. Mayo Clinic. 2020.
Available at:
https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304.
Accessed on December 18, 2020.
- The Economic Costs of Crohn's Disease and Ulcerative Colitis.
Access Economics Pty Limited. 2007. Available at:
https://www.crohnsandcolitis.com.au/site/wp-content/uploads/Deloitte-Access-Economics-Report.pdf.
Accessed on December 18, 2020.
- A Study of the Efficacy and Safety of Risankizumab in
Participants With Moderately to Severely Active Crohn's Disease.
ClinicalTrials.gov. 2020. Available at:
https://clinicaltrials.gov/ct2/show/record/NCT03105128. Accessed on
December 18, 2020.
- A Study to Assess the Efficacy and Safety of Risankizumab in
Participants With Moderately to Severely Active Crohn's Disease Who
Failed Prior Biologic Treatment. ClinicalTrials.gov. 2020.
Available at:
https://clinicaltrials.gov/ct2/show/record/NCT03104413. Accessed on
December 18, 2020.
- Duvallet, E., Sererano, L., Assier, E., et al. Interleukin-23:
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