NORTH CHICAGO, Ill.,
Aug. 18, 2021 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced that the New England Journal of
Medicine (NEJM) has published 12-week results from
the Phase 3 ADVANCE trial evaluating atogepant for the preventive
treatment of migraine in adults who meet criteria for episodic
migraine. The study, which enrolled adult participants experiencing
4 to 14 migraine days per month, found that all active treatment
arms of atogepant – 10 mg, 30 mg, and 60 mg once-daily doses – met
their primary endpoint of a statistically significant reduction in
mean monthly migraine days across the 12-week treatment period
compared to placebo.2 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.2
The full NEJM article is available at nejm.org.
Atogepant, which is currently under review by the U.S. Food and
Drug Administration (FDA), is an investigational orally
administered calcitonin gene-related peptide (CGRP) receptor
antagonist (gepant), which, if approved, will be the first and only
oral gepant specifically developed for the preventive treatment of
episodic migraine.3
"Too many people around the world face the incapacitating
challenges of migraine, which place undue burden on patients, care
partners, and health systems," said Michael
Gold, M.D., vice president, neuroscience development,
AbbVie. "At AbbVie, we are resolutely committed to advancing new
treatment options across the migraine continuum. These data
reinforce our confidence in atogepant as a potential option for the
preventive treatment of migraine."
The primary endpoint for the ADVANCE trial was change from
baseline in mean monthly migraine days across the 12-week treatment
period.1 All atogepant dose groups met the primary
endpoint and demonstrated statistically significant reductions in
mean monthly migraine days compared to placebo.1
Patients treated in the 10 mg, 30 mg, and 60 mg atogepant arms
experienced a decrease of 3.7, 3.9, and 4.2 days respectively
compared to patients in the placebo arm, who experienced a decrease
of 2.5 days (all dose groups versus placebo,
p<0.0001).1
Efficacy results for prespecified, multiplicity-controlled
secondary endpoints in the ADVANCE trial across the 12-week
treatment period include1:
- Patients treated with 10 mg, 30 mg, and 60 mg doses of
atogepant experienced a decrease in mean monthly headache days of
3.9 (baseline 8.4), 4.0 (baseline 8.8), and 4.2 (baseline 9.0) days
respectively versus a 2.5-day (baseline 8.4) decline in the placebo
arm (p<0.0001 for all doses).
- A significantly greater reduction from baseline in acute
medication use days was seen with all doses of atogepant compared
to placebo, with a decrease of 3.7, 3.7, and 3.9 days for the 10
mg, 30 mg, and 60 mg doses respectively compared to a 2.4-day
decrease with placebo (p<0.0001 for all doses).
- Across the 12-week treatment period, the trial demonstrated
that 55.6%, 58.7%, and 60.8% of patients in the 10 mg, 30 mg, and
60 mg atogepant arms respectively achieved a 50% or greater
reduction in monthly migraine days, compared to 29.0% of patients
in the placebo arm (all dose groups versus placebo,
p<0.0001).
- Improvements in the Migraine-Specific Quality of Life
Questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive
domain score were significantly greater with atogepant at all doses
(9.9, 10.1, and 10.8 point improvements, p<0.0001 for all doses)
compared to placebo at week 12.*
- Significant greater improvements in the mean monthly AIM-D**
Performance of Daily Activities domain score compared to placebo
were observed for the 30 mg and 60 mg doses, -2.5 points for the 30
mg dose (p=0.0005), and -3.3 points for the 60 mg dose
(p<0.0001).***
- Similar to the Performance of Daily Activities domain, the
Physical Impairment domain in the AIM-D score showed statistically
greater improvement for the 30 mg and 60 mg doses of atogepant
compared to placebo, -2.0 for the 30 mg dose (p=0.0021) and -2.5
for the 60 mg dose (p=0.0002).***
"Migraine symptoms can vary in frequency and severity from
person to person and from attack to attack, which is why they can
impact people's daily lives in so many different ways," said
Peter Goadsby, M.D., neurologist and
professor at University of California (Los
Angeles) and King's College, London, and an author of the atogepant ADVANCE
study NEJM article. "The novel AIM-D functional scale
administered in the ADVANCE study and the Migraine-Specific Quality
of Life Questionnaire helped us monitor the effects of migraine on
ability to perform daily activities and functions. These data,
along with the primary endpoint and other secondary endpoints, help
further our understanding of atogepant as a potential treatment
option for people living with migraine."
All doses were well tolerated. The most common adverse events
reported with a frequency ≥ 5% in at least one atogepant treatment
arm, and greater than placebo, were constipation (6.9-7.7% across
all doses versus 0.5% for placebo), nausea (4.4-6.1% across all
doses versus 1.8% for placebo), and upper respiratory tract
infection (3.9-5.7% across all doses versus 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.1
About the Phase 3 ADVANCE Study
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 preventive treatment 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, and 60 mg of atogepant once daily, or
placebo. Efficacy analyses were based on the modified
intent-to-treat (mITT) population of 873 patients.
The study results were previously announced in a July 2020 press release and first presented at
the 2020 Virtual Migraine Trust International Symposium and most
recently during the Clinical Trials Plenary Session of the 2021
American Academy of Neurology Annual Meeting.
*MSQ v2.1 measures health-related
quality of life impairments attributed to migraine for three
domains: Role Function-Restrictive, Role Function-Preventive, and
Emotional Function domain. A higher score indicates a lesser impact
of migraine on daily activities.
**The Activity Impairment in Migraine-Diary
(AIM-D) is an 11-item daily diary measure that assesses the impact
of migraine on the Performance of Daily Activities and Physical
Impairment. The AIM-D domain scores range between 0 to
100; higher scores indicate greater impact of migraine, and score
reductions from baseline indicate improvement.
***The 10 mg dose improvements were not statistically
significant.
About Migraine
Migraine is a complex, chronic disease
with recurrent attacks that are often incapacitating and
characterized by headache pain as well as neurologic and autonomic
symptoms.4 It is highly prevalent, affecting more than 1
billion people worldwide, including 39 million people in the U.S.
alone,5 and is the highest cause of disability worldwide
for people under 50 years of age.6,7 Due to the
unpredictability and fluctuation of attack frequency and severity,
migraine substantially impacts many aspects of an individual's life
both during and between attacks. Daily activities, work, school,
and personal relationships can be negatively affected, leading to a
significant burden on the person with migraine, their family,
friends, employers, and healthcare systems.
About Atogepant
Atogepant is an investigational orally
administered, CGRP receptor antagonist (gepant) specifically
developed for the preventive 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. Atogepant is
currently under review by the U.S. FDA.
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, LinkedIn or Instagram.
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:
1. Ailani J, et al. Atogepant for the
Preventive Treatment of Migraine. New England Journal of Medicine.
2021 August 19; Vol. 385, No. 8:695-706. DOI:
10.1056/NEJMoa2035908.
2. AbbVie. (2020, July 29). AbbVie
Announces Positive Phase 3 Data for Atogepant in Migraine
Prevention.
https://news.abbvie.com/news/press-releases/abbvie-announces-positive-phase-3-data-for-atogepant-in-migraine-prevention.htm
3. AbbVie. (2021, March 30). U.S. FDA
Accepts AbbVie's New Drug Application for Atogepant for the
Preventive Treatment of Migraine.
https://news.abbvie.com/news/press-releases/us-fda-accepts-abbvies-new-drug-application-for-atogepant-for-preventive-treatment-migraine.htm
4. Headache Classification Committee of the International Headache
Society (IHS) The International Classification of Headache
Disorders, 3rd edition. Cephalalgia. 2018;38:1-211.
5. Migraine Research Foundation. Migraine Facts.
https://migraineresearchfoundation.org/about-migraine/migraine-facts/#:~:text=Migraine%20is%20an%20extraordinarily%20prevalent,U.S.%20and%201%20billion%20worldwide.
6. GBD 2016 Disease and Injury Incidence and Prevalence
Collaborators. Global, regional, and national incidence,
prevalence, and years lived with disability for 328 diseases and
injuries for 195 countries, 1990-2016: a systematic analysis for
the Global Burden of Disease Study 2016. Lancet.
2017;390:1211-1259.
7. Steiner TJ, Stovner LJ, Vos T, Jensen R, Katsarava Z. Migraine
is first cause of disability in under 50s: Will health politicians
now take notice? J Headache Pain. 2018;19:17.
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