NORTH CHICAGO, Ill.,
June 2, 2021 /PRNewswire/
-- AbbVie (NYSE: ABBV) today announced positive top-line
results from the Phase 3 maintenance study, FORTIFY, showing
risankizumab 360 mg (subcutaneous [SC]; administered every eight
weeks) achieved the co-primary endpoints of endoscopic response and
clinical remission at one year in adult patients with moderate to
severe Crohn's disease.1
In this study, patients who responded to 12 weeks of
risankizumab intravenous (IV) induction treatment (in a prior
study) were re-randomized to receive risankizumab 180 mg,
risankizumab 360 mg or withdrawal from risankizumab treatment
(risankizumab IV induction-only control group).1 This
study included different sets of primary and secondary endpoints
for the U.S. analysis plan and the outside of the U.S. (OUS)
analysis plan due to regulatory requirements in the different
regions.1 The co-primary endpoints were endoscopic
response and clinical remission at week 52.1 Clinical
remission was defined by Crohn's Disease Activity Index (CDAI) in
the U.S. analysis plan and by stool frequency and abdominal pain
(SF/AP) in the OUS analysis plan.1
After one year, 47 percent of patients receiving risankizumab
360 mg achieved endoscopic response compared with 22 percent of
patients in the induction-only control group
(p<0.001).1 Significantly more patients receiving
risankizumab 360 mg achieved clinical remission (CDAI; U.S.
analysis plan), with 52 percent on risankizumab 360 mg achieving
clinical remission versus 41 percent in the induction-only
control group (p<0.01).1 Results also showed that 52
percent of patients receiving risankizumab 360 mg achieved clinical
remission (SF/AP; per OUS analysis plan) compared to 40 percent in
the induction-only control group (p=0.004).1 In
addition, 39 percent of patients receiving risankizumab 360 mg
achieved endoscopic remission compared to 13 percent of patients in
the induction-only control group (nominal p<0.001).1
Furthermore, 29 percent of risankizumab 360 mg-treated patients
achieved deep remission compared to 10 percent in the
induction-only control group (nominal p<0.001).1 Deep
remission is a stringent endpoint defined by clinical remission
(CDAI) and endoscopic remission, both measured in the same
patient.1
"In our global clinical trial program to-date, risankizumab has
shown clinically meaningful rates of endoscopic response and
clinical remission among patients living with moderate to severe
Crohn's disease," said Michael Severino, M.D., vice chairman
and president, AbbVie. "These results represent another step
towards the development of risankizumab for these patients, many of
whom do not find sufficient disease control with current
treatments."
Risankizumab 180 mg (SC; administered every eight weeks) met the
co-primary endpoints in the U.S. analysis plan, but not in the OUS
analysis plan.1 In this study, 47 percent of patients
receiving risankizumab 180 mg achieved endoscopic response compared
with 22 percent of patients in the induction-only control group
(p<0.001 per U.S. analysis plan; nominal p<0.001 per OUS
analysis plan).1 Furthermore, 55 percent of patients
receiving risankizumab 180 mg achieved clinical remission (CDAI;
U.S. analysis plan) compared to 41 percent of patients in the
induction-only control group (p<0.01).1 Additionally,
46 percent of patients receiving risankizumab 180 mg achieved
clinical remission (SF/AP; per OUS analysis plan) compared to 40
percent in the induction-only control group (nominal
p=0.124).1 At one year, 30 percent of patients receiving
risankizumab 180 mg achieved endoscopic remission compared to 13
percent of patients in the induction-only control group (nominal
p<0.001).1 Results also showed that 25 percent of
risankizumab 180 mg-treated patients achieved deep remission
compared to 10 percent in the induction-only control group (nominal
p<0.001).1
"Nearly half of patients were able to achieve endoscopic
response after one year of maintenance treatment with
risankizumab," said Marc Ferrante,
M.D., Ph.D., Department of Gastroenterology and Hepatology,
University Hospitals Leuven, Belgium. "In a progressive, chronic disease
where many people struggle to ever achieve endoscopic response, the
rates achieved in this study are encouraging for patients."
FORTIFY Efficacy
Results at Week 52a,1
|
|
Risankizumab 360
mg
(n=141)
|
Risankizumab 180
mg
(n=157)
|
Risankizumab IV
induction-only
(control
group)
(n=164)
|
Endoscopic
Responseb
|
47%g
|
47%k
|
22%
|
Clinical Remission
(CDAI)c
|
52%h
|
55%h
|
41%
|
Clinical Remission
(SF/AP)d
|
52%i
|
46%l
|
40%
|
Endoscopic
Remissione
|
39%j
|
30%j
|
13%
|
Deep
Remissionf
|
29%j
|
25%j
|
10%
|
a The
primary endpoints were 52-week endoscopic response (for both the
U.S. and OUS analysis plans) and clinical remission (CDAI) for the
U.S. analysis plan and clinical remission (SF/AP) for the OUS
analysis plan.
|
b
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 a central
reviewer.
|
c Clinical
remission (CDAI) is defined as a CDAI score of <150. This
is a co-primary endpoint for the U.S. analysis plan
and a secondary endpoint for the OUS analysis plan.
|
d Clinical
remission (SF/AP) is based on average daily stool frequency and
average daily abdominal pain score. This is a co-primary
endpoint for the OUS analysis plan and a secondary endpoint for the
U.S. analysis plan.
|
e
Endoscopic remission is defined as SES-CD ≤4 and at least a 2-point
reduction versus baseline and no subscore greater than 1 in any
individual component, as scored by a central reviewer. This is a
secondary endpoint in both the U.S. and OUS analysis
plans.
|
f Deep
remission is defined by clinical remission (CDAI) and endoscopic
remission, both measured in the same patient. This is a secondary
endpoint in both the U.S. and OUS analysis plans.
|
g
p<0.001 comparing to risankizumab induction-only control
group. Statistically significant for both U.S. and OUS
analysis plans.
|
h
p<0.01 comparing to risankizumab induction-only control
group. Statistically significant for the U.S. analysis plan.
Nominal p-value for the OUS analysis plan.
|
i
p<0.01 comparing to risankizumab induction-only control
group. Statistically significant for both U.S. and OUS
analysis plans.
|
j
p<0.001 comparing to risankizumab induction-only control group.
Nominal p-value for both U.S. and OUS analysis plans.
|
k
p<0.001 comparing to risankizumab induction-only control group.
Statistically significant for the U.S. analysis plan. Nominal
p-value for the OUS analysis plan.
|
l Not
statistically significant.
|
In FORTIFY, during the pivotal 52-week maintenance period, the
safety profile of both doses of risankizumab was generally
consistent with the known safety profile of
risankizumab.1-7 No new safety risks were
observed.1-7 Serious adverse events (SAEs) occurred in
12.3 percent of patients in the risankizumab 180 mg group and 13.4
percent of patients in the risankizumab 360 mg group compared to
12.5 percent of patients in the induction-only control
group.1 The most common adverse events (AEs) observed in
the risankizumab treatment groups were exacerbation of Crohn's
disease, nasopharyngitis and arthralgia.1 Rates of
serious infections were 2.8 percent and 4.5 percent in those
treated with risankizumab 180 mg or 360 mg, respectively, and 3.8
percent in the induction-only control group.1 The rates
of AEs leading to discontinuation of the study drug were 1.7
percent and 3.4 percent of patients treated with risankizumab 180
mg and 360 mg, respectively, compared with 3.3 percent in the
induction-only control group.1 There were two
adjudicated major adverse cardiovascular events (MACE) reported at
the time of database lock.1 One event occurred in the
induction-only control arm and the other occurred in the
risankizumab 360 mg arm.1 Both events were assessed by
study investigators to be unrelated to the study drug and both
patients had pre-existing risk factors.1 Both patients
continued in the trial.1 There were no anaphylactic
reaction events or deaths reported.1
These top-line results are from the 52-week pivotal portion of
the FORTIFY Phase 3 study, which was designed to evaluate the
efficacy and safety of risankizumab as maintenance therapy versus
risankizumab induction-only in patients with moderate to severe
Crohn's disease who responded to risankizumab induction treatment
in the ADVANCE or MOTIVATE induction studies.1 Top-line
results from both of these studies were announced in
January 2021. Full results from the
FORTIFY study 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.
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.11-13 It is a progressive disease, meaning it
gets worse over time.12,13 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.14
About the FORTIFY Study1,8
The FORTIFY study is a Phase 3, multicenter, randomized,
double-blind, control group, 52-week maintenance and an open-label
extension study designed to evaluate the efficacy and safety of
risankizumab in adults with moderate to severe Crohn's disease.
This study had a re-randomized withdrawal design in which all
patients received risankizumab IV induction and those who responded
to risankizumab were re-randomized to receive risankizumab 180 mg
SC, risankizumab 360 mg SC or withdrawal from risankizumab
treatment (induction-only control group). For those randomized to
the withdrawal from risankizumab treatment (induction-only control
group), the rest of the study duration was a risankizumab washout.
The objective of this Phase 3 study is to evaluate the efficacy and
safety of risankizumab 180 mg and 360 mg as maintenance therapy
versus withdrawal from risankizumab treatment (control) in patients
with moderate to severe Crohn's disease who responded to
risankizumab IV induction treatment in the ADVANCE and MOTIVATE
studies.
This study included different sets of primary and secondary
endpoints for the U.S. analysis plan and OUS analysis plan due to
regulatory requirements in the different regions. The co-primary
endpoints were achievement of endoscopic response and clinical
remission at week 52. Clinical remission was defined by CDAI, which
was measured by a CDAI score less than 150, in the U.S. analysis
plan and defined by SF/AP, which was measured by daily stool
frequency and abdominal pain score, in the OUS analysis plan.
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. Endoscopic remission is defined as SES-CD ≤4 and at
least a two-point reduction versus baseline and no sub-score
greater than one in any individual variable, as scored by a central
reviewer. Deep remission is defined by clinical remission (CDAI)
and endoscopic remission, both measured in the same patient.
More information can be found on
www.clinicaltrials.gov (NCT03105102).
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 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, administered by prefilled
pen or prefilled syringe at week 0 and 4, and every 12 weeks
thereafter. SKYRIZI was also approved in psoriasis by the European
Commission in April 2019. Phase 3
trials of SKYRIZI in psoriatic arthritis, Crohn's disease and
ulcerative colitis are ongoing.8-10 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 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: ABVRRTI722293.
- 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. 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.
- AbbVie. Data on File: ABVRRTI71474.
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- A Study of the Efficacy and Safety of Risankizumab in
Participants With Crohn's Disease. ClinicalTrials.gov. 2021.
Available at:
https://clinicaltrials.gov/ct2/show/NCT03105102. Accessed
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- 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://clinicaltrials.gov/ct2/show/NCT03671148. Accessed on
May 21, 2021.
- 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. 2021. Available at:
https://clinicaltrials.gov/ct2/show/record/NCT03398148. Accessed on
May 21, 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.
- 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 May 21, 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 May 21, 2021.
- 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 May 21, 2021.
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