NORTH CHICAGO, Ill.,
March 30, 2021 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced that the U.S. Food and Drug
Administration (FDA) has accepted its New Drug Application (NDA)
for atogepant, an investigational orally administered calcitonin
gene-related peptide (CGRP) receptor antagonist (gepant), for the
preventive treatment of migraine in adults who meet criteria for
episodic migraine. AbbVie anticipates a regulatory decision in late
Q3 2021.
Migraine is a complex, chronic disease with attacks that are
often incapacitating and can include headache pain as well as
neurologic and autonomic symptoms.3 Migraine symptoms
and severity range widely among individuals.
The NDA is supported by data from a robust clinical program
evaluating the efficacy, safety and tolerability of orally
administered atogepant in nearly 2,500 patients who experience 4-14
migraine days per month including but not limited to the pivotal
Phase 3 ADVANCE study, the pivotal Phase 2b/3 study, and the Phase 3 long-term safety
study.
"With the integration of Allergan, AbbVie is now a committed
leader in migraine with an almost 25-year history in migraine
research. We look forward to potentially adding a new treatment
option to our portfolio that will help more people with migraine,"
said Michael Gold, MD, vice
president, neuroscience development, AbbVie. "We believe atogepant
is an advancement with the potential to offer meaningful benefits
as a safe, effective oral preventive treatment option. Despite the
availability of other migraine treatment options, the medical
community and people living with migraine recognize the unmet need
of those who face the unpredictable and debilitating realities of
this disease."
In the Phase 3 ADVANCE study, all active treatment arms of
atogepant met their primary endpoint of a statistically significant
reduction in mean monthly migraine days over a 12-week treatment
period. Also, the 30 and 60 mg doses met all six secondary
endpoints with statistical significance. This study followed
positive results from the Phase 2b/3
study that met the same primary endpoint across all doses and
dosing regimens. The Phase 3 long-term safety study evaluated
safety and tolerability of 60 mg oral atogepant administered daily
over 52 weeks. The Phase 3 long-term safety study will be presented
at the American Academy of Neurology 2021 Virtual Annual Meeting.
Results from the Phase 2b/3
study and the Phase 3 ADVANCE study were previously
announced.1,4
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 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
significant reductions in mean monthly migraine days compared to
placebo. Patients treated in the 10 mg, 30 mg, and 60 mg atogepant
arms experienced a decrease of 3.69, 3.86, and 4.2 days,
respectively, 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%, and 60.8% of patients in the 10 mg, 30 mg, and
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).
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 vs. 0.5% for placebo), nausea (4.4-6.1% across all doses
vs. 1.8% for placebo), and upper respiratory tract infection
(3.9-5.7% across all doses 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.
The study results were announced in a July 2020 press release and presented at the 2020
Virtual Migraine Trust International Symposium.
About the Phase 2b/3 CGP-MD-01
Study
The pivotal Phase 2b/3
clinical trial evaluating the efficacy, safety and tolerability of
orally administered atogepant demonstrated that all active
treatment arms met the primary endpoint with a statistically
significant reduction from baseline in mean monthly migraine days
compared with placebo across the 12-week treatment period in those
with 4 to 14 migraine days per month. The results were announced in
a June 2018 press release and were
also presented at the 2019 American Headache Society Annual
Meeting.
About the Phase 3 Long-Term Safety Study
The Phase 3,
multicenter, randomized, open-label study evaluated the long-term
safety and tolerability of 60 mg oral atogepant administered daily
over 52 weeks for the preventive treatment of migraine in adults
with 4-14 migraine days per month. Further details on the study
will be presented at the American Academy of Neurology 2021 Virtual
Annual Meeting.
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.2 It is highly prevalent, affecting more than 1
billion people worldwide, including 39 million people in the U.S.
alone,2 and is the highest cause of disability worldwide
for people under 50 years of age.5,6 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.
About AbbVie Leadership in Migraine
AbbVie, a leader
in the migraine space, markets BOTOX® (onabotulinumtoxinA), the
first FDA-approved, preventive treatment for adults with chronic
migraine and UBRELVY® (ubrogepant), the first FDA-approved oral
calcitonin gene-related peptide (CGRP) receptor antagonist
(gepant), which is indicated for the acute treatment of migraine
with or without aura in adults.
BOTOX® Indication
BOTOX® is a prescription medicine
that is injected into muscles and used:
- To prevent headaches in adults with Chronic Migraine who have
15 or more days each month with headache lasting 4 or more hours
each day in people 18 years or older
It is not known whether BOTOX® is safe and effective to prevent
headaches in patients with migraine who have 14 or fewer headache
days each month (episodic migraine).
IMPORTANT SAFETY INFORMATION
BOTOX® may cause serious side effects that can be life
threatening. Get medical help right away if you have any of these
problems any time (hours to weeks) after injection of
BOTOX®:
- Problems swallowing, speaking, or breathing, due to
weakening of associated muscles, can be severe and result in loss
of life. You are at the highest risk if these problems are
pre-existing before injection. Swallowing problems may last for
several months
- Spread of toxin effects. The effect of botulinum toxin
may affect areas away from the injection site and cause serious
symptoms including: loss of strength and all-over muscle weakness,
double vision, blurred vision and drooping eyelids, hoarseness or
change or loss of voice, trouble saying words clearly, loss of
bladder control, trouble breathing, and trouble swallowing
There has not been a confirmed serious case of spread of toxin
effect away from the injection site when BOTOX® has been used at
the recommended dose to treat chronic migraine.
BOTOX® may cause loss of strength or general muscle weakness,
vision problems, or dizziness within hours to weeks of taking
BOTOX®. If this happens, do not drive a car, operate machinery,
or do other dangerous activities.
Do not receive BOTOX® if you: are allergic to any of its
ingredients in BOTOX® (see Medication Guide for ingredients); had
an allergic reaction to any other botulinum toxin product such as
Myobloc® (rimabotulinumtoxinB), Dysport® (abobotulinumtoxinA), or
Xeomin® (incobotulinumtoxinA); have a skin infection at the planned
injection site.
The dose of BOTOX® is not the same as, or comparable to, any
other botulinum toxin product.
Serious and/or immediate allergic reactions have been
reported, including itching, rash, red itchy welts, wheezing,
asthma symptoms, or dizziness or feeling faint. Get medical help
right away if you experience symptoms; further injection of BOTOX®
should be discontinued.
Tell your doctor about all your muscle or nerve
conditions such as ALS or Lou
Gehrig's disease, myasthenia gravis, or Lambert-Eaton
syndrome, as you may be at increased risk of serious side effects
including difficulty swallowing and difficulty breathing from
typical doses of BOTOX®.
Tell your doctor about all your medical conditions, including
if you: have or have had bleeding problems; have plans to have
surgery; had surgery on your face; weakness of forehead muscles;
trouble raising your eyebrows; drooping eyelids; any other abnormal
facial change; are pregnant or plan to become pregnant (it is not
known if BOTOX® can harm your unborn baby); are breastfeeding or
plan to (it is not known if BOTOX® passes into breast milk).
Tell your doctor about all the medicines you take,
including prescription and over-the-counter medicines, vitamins,
and herbal supplements. Using BOTOX® with certain other medicines
may cause serious side effects. Do not start any new medicines
until you have told your doctor that you have received BOTOX® in
the past.
Tell your doctor if you have received any other botulinum toxin
product in the last 4 months; have received injections of botulinum
toxin such as Myobloc®, Dysport®, or Xeomin® in the past (tell your
doctor exactly which product you received); have recently received
an antibiotic injection; take muscle relaxants; take allergy or
cold medicines; take sleep medicine; take aspirin-like products or
blood thinners.
Other side effects of BOTOX® include: dry mouth,
discomfort or pain at injection site, tiredness, headache, neck
pain, eye problems: double vision, blurred vision, decreased
eyesight, drooping eyelids, swelling of your eyelids, dry eyes;
drooping eyebrows.
For more information refer to the Medication Guide or talk with
your doctor.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit www.fda.gov/medwatch or
call 1-800-FDA-1088.
Please see BOTOX® full Prescribing Information, including
Boxed Warning and Medication Guide.
UBRELVY® Indication
UBRELVY (ubrogepant) is indicated for the acute treatment of
migraine with or without aura in adults. UBRELVY is not indicated
for the preventive treatment of migraine.
IMPORTANT SAFETY INFORMATION
Contraindication: Concomitant use of strong CYP3A4
inhibitors (eg, ketoconazole, itraconazole, clarithromycin).
Adverse Reactions: The most common adverse reactions were
nausea (4%) and somnolence (3%).
Please see UBRELVY full Prescribing Information.
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 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:
1. 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
2. Migraine Research Foundation. Migraine Facts.
https://migraineresearchfoundation.org/about-migraine/migraine-facts/#:~:text=Migraine%20is%20an%20extraordinarily%20prevalent,U.S.%20and%201%20billion%20worldwide.
3. Headache Classification Committee of the International Headache
Society (IHS) The International Classification of Headache
Disorders, 3rd edition. Cephalalgia. 2018;38:1-211.
4. Allergan, an AbbVie Company. (2018, June
11). Allergan's Oral CGRP Receptor Antagonist Atogepant
Demonstrates Robust Efficacy and Safety in Episodic Migraine
Prevention in a Phase 2b/3 Clinical
Trial.
https://www.prnewswire.com/news-releases/allergans-oral-cgrp-receptor-antagonist-atogepant-demonstrates-robust-efficacy-and-safety-in-episodic-migraine-prevention-in-a-phase-2b3-clinical-trial-300663770.html
5. 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.
6. 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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SOURCE AbbVie