NORTH CHICAGO, Ill.,
May 24, 2021 /PRNewswire/ --
Late-breaking data analyses presented by AbbVie (NYSE: ABBV) at
Digestive Disease Week® (DDW) Virtual Conference 2021
showed significantly greater proportions of patients with
moderately to severely active Crohn's disease treated with both
doses of investigational risankizumab (600 mg or 1200 mg) met the
co-primary endpoints of clinical remission and endoscopic response
at week 12 compared to placebo (p<0.001 for each) in two Phase 3
induction studies.1 This is the first presentation of
data from these two studies, ADVANCE and MOTIVATE, following the
announcement of top-line data earlier this year.
The ADVANCE study included patients with past intolerance or
inadequate response to conventional therapy (non-bio-IR) and/or
biologic therapy (bio-IR). The MOTIVATE trial evaluated only bio-IR
patients. In the ADVANCE study, risankizumab showed efficacy
regardless of prior treatment status by subgroup analysis in
patients with moderate to severe Crohn's disease, and non-bio-IR
patients had numerically higher rates of efficacy compared to
bio-IR patients.1*
"Many people with Crohn's disease, an unpredictable condition
that can cause significant physical, emotional and economic burden,
do not achieve disease control with current treatments," said
Remo Panaccione, M.D., professor of
medicine and director of the IBD unit, University of Calgary. "We are pleased to present
data at DDW that demonstrates risankizumab helps significantly more
patients to achieve clinical remission and endoscopic response
at week 12 compared to placebo."
These and additional data were presented at DDW 2021 as part of
the "Clinical Science Late-Breaking Abstract Plenary" session
(Abstract #775a) on Sunday, May 23, 2:32 pm - 2:46 p.m. CT.
ADVANCE Efficacy
Results at Week 121
|
Endpoint
Population
|
Risankizumab
600
mg
%
(n/N)
|
Risankizumab
1200
mg
%
(n/N)
|
Placebo
%
(n/N)
|
Clinical Remission
per CDAI (U.S. protocol)a
|
Overall
|
45.1
(152/336)*
|
41.9
(142/339)*
|
24.6
(43/175)*
|
Non-Bio-IR
|
48.6
(69/142)
|
48.6
(69/142)
|
23.1
(18/78)
|
Bio-IR
|
42.6
(83/194)
|
37.1
(73/197)
|
25.8
(25/97)
|
Clinical Remission
per SF/AP (ex-U.S. protocol)b
|
Overall
|
43.5
(146/336)*
|
41.3
(140/339)*
|
21.1
(37/175)*
|
Non-Bio-IR
|
47.9
(68/142)
|
45.1
(64/142)
|
19.2
(15/78)
|
Bio-IR
|
40.2
(78/194)
|
38.6
(76/197)
|
22.7
(22/97)
|
Endoscopic
Responsec
|
Overall
|
40.3
(135/336)*
|
32.2
(109/339)*
|
12.0
(21/175)*
|
Non-Bio-IR
|
50.2
(71/142)
|
44.0
(62/142)
|
12.8
(10/78)
|
Bio-IR
|
33.0
(64/194)
|
23.7
(47/197)
|
11.4
(11/97)
|
|
|
MOTIVATE Efficacy
Results at Week 121
|
Endpoint
Population
|
Risankizumab
600
mg
%
(n/N)
|
Risankizumab
1200
mg
%
(n/N)
|
Placebo
%
(n/N)
|
Clinical Remission
per CDAI (U.S. protocol)a
|
Bio-IR
|
42.2
(80/191)*
|
40.8
(78/191)*
|
19.3
(36/187)*
|
Clinical Remission
per SF/AP (ex-U.S. protocol)b
|
Bio-IR
|
34.6
(66/191)*
|
39.3
(75/191)*
|
19.3
(36/187)*
|
Endoscopic
Responsec
|
Bio-IR
|
28.8
(55/191)*
|
34.1
(65/191)*
|
11.2
(21/187)*
|
* All differences between the overall risankizumab dose groups
and placebo are statistically significant, with p-values <0.001.
Statistical testing was not performed for the subgroups, non-bio-IR
and bio-IR, in the ADVANCE study.
a Clinical remission per CDAI (Crohn's Disease
Activity Index) is defined as CDAI score of <150.
b Clinical remission per SF (stool frequency)/AP
(abdominal pain) (also referred to as PRO-2) is defined as average
daily SF score of ≤2.8 and daily AP score of ≤1, not worse than
baseline for both.
c Endoscopic response is defined as a decrease in
simple endoscope score for Crohn's disease (SES-CD) >50
percent from baseline (or for patients with isolated ileal
disease and a baseline SES-CD of 4, ≥2-point reduction from
baseline).
During the 12-week induction period, the safety profile of
risankizumab in both studies was generally consistent with the
known safety profile of risankizumab from previous clinical
trials.1 No new safety risks were observed.
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.1 The most common AEs observed in
the risankizumab treatment groups were headache, arthralgia and
nasopharyngitis. 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.1 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.1 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. There were
no adjudicated MACE or adjudicated anaphylactic reaction events
reported.1
Results from these studies are being submitted to journals for
publication. 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.2,4,5 It is a progressive disease, meaning
it gets worse over time.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.4
About the ADVANCE and MOTIVATE
Studies1,6,7
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 outside U.S. (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. 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.8,9 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.
8,9 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, ulcerative colitis
and psoriatic arthritis are ongoing.6,7,10,11 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 States9
SKYRIZI is indicated for the treatment of moderate to severe
plaque psoriasis in adults who are candidates for systemic therapy
or phototherapy.
Important Safety Information9
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 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:
- D'Haens G, Panaccione R, Colombel JF, et al. Risankizumab
induction therapy in patients with moderate-to-severe Crohn's
disease: results from the ADVANCE and MOTIVATE phase 3 studies.
Presented at Digestive Disease Week® (DDW) Virtual
Conference 2021, May 21–23.
- 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 April 9, 2021.
- 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 April 9, 2021.
- The Economic Cost 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 April 9, 2021.
- 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.
- A Study of the Efficacy and Safety of Risankizumab in
Participants With Moderately to Severely Active Crohn's Disease.
ClinicalTrials.gov 2021. Available at
https://www.clinicaltrials.gov/ct2/show/NCT03105128. Accessed on
April 9, 2021.
- 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. Available at
https://www.clinicaltrials.gov/ct2/show/NCT03104413. Accessed on
April 9, 2021.
- Duvallet E, Sererano L, Assier E, et al. Interleukin-23: a key
cytokine in inflammatory diseases. Ann Med. 2011. Nov
43(7):503-11.
- SYRIZI (risankizumab) [Package Insert]. North Chicago, Ill.: AbbVie Inc.
- A Study to Assess the Safety and Efficacy of Risankizumab for
Maintenance in Moderate to Severe Plaque Type Psoriasis
(LIMMITLESS). ClinicalTrials.gov 2021. Available at:
https://www.clinicaltrials.gov/ct2/show/NCT03047395. Accessed on
April 9, 2021.
- 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 2021. Available at:
https://www.clinicaltrials.gov/ct2/show/NCT03671148. Accessed on
April 9, 2021.
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