NORTH CHICAGO, Ill.,
July 29, 2020 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced that the Phase 3 ADVANCE trial
evaluating the investigational medicine atogepant, an orally
administered calcitonin gene-related peptide (CGRP) receptor
antagonist (gepant) met its primary endpoint of statistically
significantly greater reduction in mean monthly migraine days,
compared to placebo, for all doses across the 12-week treatment
period. With these results, combined with the prior positive Phase
2/3 trial, AbbVie plans to move forward with regulatory submissions
in the United States and other
countries. Full data results will be presented at an upcoming
medical congress and/or published in a peer-reviewed journal.
"Migraine attacks can be debilitating, but migraine is a
treatable disease, and people living with it are not alone in their
battle to control it," said Thomas J.
Hudson, M.D., senior
vice president of R&D and chief scientific officer, AbbVie.
"With the results from these trials, we aim to provide a safe and
effective preventive treatment that offers patients and healthcare
providers a simple, once daily oral treatment that works
specifically by blocking CGRP receptors and preventing
migraine."
About the Pivotal ADVANCE Trial
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 compared to 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 (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. There were no hepatic safety issues identified in
this trial.
About the Phase 2/3 CGP-MD-01 Study
The Phase 2/3
clinical trial evaluating the efficacy, safety, and tolerability of
orally administered atogepant, demonstrated that all active
treatment arms of atogepant met the primary endpoint with a
statistically significant reduction from baseline in mean monthly
migraine days compared with placebo across the 12 week-week
treatment period (10 mg QD vs placebo, p=0.0236; 30 mg QD vs
placebo, p=0.0390; 60 mg QD vs placebo, p=0.0390; 30 mg BID vs
placebo; p=0.0034, 60 mg BID vs placebo, p=0.0031).* The
results were announced in a press release issued in
June 2018.
About Migraine
Migraine is a complex, chronic disease
with episodic attacks that are often incapacitating and
characterized by headache pain as well as neurologic and autonomic
symptoms.[1] It is highly prevalent, affecting more than
one billion people worldwide, and is the highest cause of
disability worldwide for people under 50 years of
age.[2],[3] Due to the unpredictability and
fluctuation of attack frequency and severity, migraine has
substantial impact on many aspects of an individual's life both
during and between attacks. Daily activities, work, school, and
personal relationships are negatively affected, leading to a
significant burden on the person with migraine, their family, and
friends, and often extending to employers and healthcare
systems.
About Atogepant
Atogepant is an 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® Indications
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 or 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,
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 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.
* The reported p-values are adjusted for multiple
comparisons by controlling the overall type I error rate of the
study at 5%, 2-sided.
1 Headache Classification Committee of the
International Headache Society (IHS) The International
Classification of Headache Disorders, 3rd edition.
Cephalalgia. 2018;38:1-211.
2 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.
3 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