- The submission is based on two pivotal Phase 3 studies
evaluating atogepant in adult patients with episodic and chronic
migraine
- If approved, atogepant would be the first daily oral
calcitonin gene-related peptide (CGRP) receptor antagonist (gepant)
for the prophylaxis of migraine in Europe
- AbbVie would become the only company with a portfolio of
medicines to offer two treatments for those with chronic migraine,
one oral and one injectable
NORTH CHICAGO, Ill.,
July 18, 2022 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced it has submitted a marketing
authorization application (MAA) to the European Medicines Agency
(EMA) for atogepant for the prophylaxis of migraine in adult
patients who have at least four migraine days per month. The
application is supported by the pivotal Phase 3 ADVANCE and
PROGRESS studies evaluating the safety, efficacy, and tolerability
of atogepant in adult patients with episodic migraine and chronic
migraine, respectively.1,2
Migraine is a complex neurological disease and one of the
leading causes of disability worldwide.3 It is highly
prevalent, affecting more than 1 billion people
worldwide,3 including an estimated 11.4 percent of
the population in Europe.4 If approved, atogepant
would be the first daily oral CGRP receptor antagonist for the
prophylaxis of migraine for adult patients in Europe.
"Far too many people around the world are impacted from the
debilitating challenges of migraine, which places a significant
social and work-life burden for patients and care partners," said
Michael Gold, M.D., therapeutic area
head, neuroscience development, AbbVie. "At AbbVie, we are
committed to advancing science to provide patients impacted by
migraine with effective treatment options. If approved, atogepant
will provide a prophylactic treatment option for adult migraine
patients suffering for more than four days a month."
The pivotal, Phase 3, multicenter, randomized, double-blind,
placebo-controlled, parallel-group ADVANCE trial evaluated the
efficacy, safety, and tolerability of once daily (QD) oral
atogepant for the prophylaxis of episodic migraine. The study met
its primary endpoint of a statistically significant reduction in
mean monthly migraine days across the 12-week treatment period
compared to placebo. This was found across all active treatment
arms of atogepant – 10 mg, 30 mg, and 60 mg QD doses. The adult
patients enrolled met the International Classification of Headache
Disorders (ICHD) criteria for a diagnosis of migraine with or
without aura. The study also found that a greater proportion of
atogepant-treated participants achieved at least a 50% reduction in
mean monthly migraine days for all doses compared to placebo and
met other key secondary endpoints.
The pivotal, Phase 3, global, randomized, double-blind,
placebo-controlled, parallel-group PROGRESS study, evaluating the
safety, efficacy, and tolerability of oral atogepant in adult
patients for the prophylaxis of chronic migraine, met its primary
endpoint of statistically significant reduction from baseline in
mean monthly migraine days compared to placebo across the 12-week
treatment period. The trial also demonstrated that treatment with
atogepant 60 mg once daily (QD) and 30 mg daily (BID), resulted in
statistically significant improvements in all secondary endpoints.
This includes a key secondary endpoint that measured the proportion
of patients that achieved at least a 50 percent reduction in mean
monthly migraine days across the 12-week treatment period.
In both, the Phase 3 PROGRESS and Phase 3 ADVANCE studies, all
doses were well tolerated, and the overall safety profiles were
consistent with safety findings observed in previous studies for
the prophylaxis of episodic migraine and chronic migraine
populations. The most common adverse events were constipation and
nausea.
The atogepant MAA will be reviewed by the Committee for
Medicinal Products for Human Use, which will issue an opinion that
will be valid for all member states of the European Union, as well
as Iceland, Lichtenstein,
Northern Ireland and Norway.
About Atogepant
Atogepant is an orally administered, CGRP receptor antagonist
(gepant) specifically developed for the prophylaxis treatment of
migraine. CGRP and its receptors are expressed in regions of the
nervous system associated with migraine pathophysiology. Studies
have shown that CGRP levels are elevated during migraine attacks
and selective CGRP receptor antagonists confer clinical benefit in
migraine.
About the Phase 3 ADVANCE Clinical
Trial1
The pivotal Phase 3, multicenter, randomized, double-blind,
placebo-controlled, parallel-group trial was designed to evaluate
the efficacy, safety, and tolerability of oral atogepant for the
prevention of migraine in those with 4 to 14 migraine days per
month. A total of 910 patients were randomized to one of four
treatment groups evaluating 10 mg, 30 mg, or 60 mg of atogepant
once daily, or placebo. Efficacy analyses were based on the
modified intent-to-treat (mITT) population of 873 patients.
The primary endpoint was change from baseline in mean monthly
migraine days across the 12-week treatment period. All atogepant
dose groups met the primary endpoint and demonstrated statistically
significantly greater decreases in mean monthly migraine days
compared to placebo. Patients treated in the 10 mg/30 mg/60 mg
atogepant arms experienced a decrease of 3.69/3.86/4.2 days,
respectively, all compared to patients in the placebo arm, who
experienced a decrease of 2.48 days (all dose groups vs. placebo,
p=<.0001).
A key secondary endpoint measured the proportion of patients
that achieved at least a 50% reduction in mean monthly migraine
days across the 12-week treatment period. The trial demonstrated
that 55.6%/58.7%/60.8% of patients in the 10 mg/30 mg/60 mg
atogepant arms, respectively, achieved at least a 50%
reduction, compared to 29.0% of patients in the placebo arm (all
dose groups vs. placebo, p=<.0001).
Additional secondary endpoints measured across the 12-week
treatment period included change from baseline in mean monthly
headache days, mean monthly acute-medication use days, and mean
monthly performance of daily activities and physical impairment
domain scores of the Activity Impairment in Migraine-Diary
(AIM-D), and change from baseline in the Migraine-Specific Quality
of Life Questionnaire (MSQ) Role Function-Restrictive domain score
at week 12. The trial demonstrated that treatment with 30 mg and 60
mg doses resulted in statistically significant improvements in all
secondary endpoints, while treatment with the 10 mg dose resulted
in statistically significant improvements in four out of the six
secondary endpoints.
No new safety risks were observed compared to the safety profile
observed in the previous trial evaluating atogepant. Serious
adverse events occurred in 0.9% of patients treated in the
atogepant 10 mg arm and 0.9% of patients in the placebo arm. No
patients in the atogepant 30 mg or 60 mg treatment arms experienced
a serious adverse event. The most common adverse events reported
with a frequency ≥ 5% in at least one atogepant treatment arm, and
greater than placebo, were constipation (7.7%, 7.0% and 6.9% in the
10 mg/30 mg/60 mg atogepant arms, respectively vs. 0.5% for
placebo), nausea (5.0%, 4.4% and 6.1% in the 10 mg/30 mg/60 mg
atogepant arms, respectively vs. 1.8% for placebo), and upper
respiratory tract infection (4.1%, 5.7% and 3.9% in the 10 mg/30
mg/60 mg atogepant arms, respectively vs. 4.5% for
placebo). The majority of cases of constipation, nausea and
upper respiratory tract infection were mild or moderate in severity
and did not lead to discontinuation. There were no hepatic safety
issues identified in this trial.
About the Phase 3 PROGRESS Clinical
Trial2
The Phase 3 PROGRESS clinical trial evaluated the safety,
tolerability and efficacy of oral atogepant for the prophylaxis
treatment of chronic migraine. The patient population for the study
included patients with a diagnosis of chronic migraine for at least
one year, and ≥ to 15 headache days with eight migraine
days in the 28 days prior to randomization. The primary endpoint
measured the reduction from baseline in mean monthly migraine days
compared to placebo, for both doses, including 60 mg once daily
(QD) and 30 mg twice daily (BID), across a 12-week treatment
period. The overall safety profile of the Phase 3 PROGRESS study
was consistent with safety findings observed in previous studies in
an episodic migraine population.
Key secondary endpoints for all
regions included: Change from baseline in mean monthly
headache days across the 12-week of treatment period (baseline is
defined as the number of migraine days during the last 28 days
prior to the randomization date); Change from baseline in mean
monthly acute medication use days across the 12-week treatment
period (baseline is defined as the number of migraine days during
the last 28 days prior to the randomization date); Proportion of
participants with at least a 50% reduction in mean monthly migraine
days across the 12-week treatment period; and change from baseline
in MSQ v2.1 Role Function-Restrictive domain score at Week 12. The
MSQ v2.1 is a questionnaire designed to measure health-related
quality of life impairments attributed to migraine in the past four
weeks. It is divided into three domains, assessing how a patient's
daily, social, and work activities are limited by migraine; how
migraine prevents these activities; and assesses the emotional
function related with migraine.
For a full listing of secondary endpoints across all regions,
please go to www.clinicaltrials.gov (NCT03855137).
About AbbVie in Neuroscience
At AbbVie, our commitment to preserving personhood for those
living with neurological and psychiatric disorders is unwavering.
Every challenge in this uncharted territory drives us to discover
and deliver solutions for patients, care partners and clinicians.
AbbVie's Neuroscience portfolio consists of approved therapies and
a robust pipeline in neurological and psychiatric disorders,
including Alzheimer's disease, bipolar disorder and depression,
cervical dystonia, major depressive disorder, migraine, Parkinson's
disease, spinal cord injuries, post-stroke spasticity,
schizophrenia, stroke and others.
We have a strong investment in neuroscience research to help us
better understand the pathophysiology of neurological and
psychiatric disorders and identify targets for potential
disease-modifying therapeutics aimed at making a difference in
people's lives. For more information, visit www.abbvie.com.
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 2021 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.
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|
112-Week
Placebo-controlled Study of Atogepant for the Preventive Treatment
of Migraine in Participants With Episodic Migraine. Available at:
https://www.clinicaltrials.gov/ct2/show/NCT03777059. Accessed on
July 6, 2022.
|
2Efficacy,
Safety, and Tolerability, of Atogepant for the Prevention of
Chronic Migraine. ClinicalTrials.gov. Available at:
https://www.clinicaltrials.gov/ct2/show/NCT03855137?term=NCT03855137&draw=2&rank=1.
Accessed on July 6, 2022.
|
3 The Facts
About Migraine. American Migraine Foundation. Available at:
https://americanmigrainefoundation.org/resource-library/migraine-facts/
. Accessed on July 6, 2022.
|
4
Woldeamanuel YW, Cowan RP. Migraine affects 1 in 10 people
worldwide featuring recent rise: a systematic review and
meta-analysis of community-based studies involving 6 million
participants. J Neurol Sci. 2017;372:307–315.
doi: 10.1016/j.jns.2016.11.071.
|