- Submission is based on
pivotal Phase 3 PROGRESS chronic migraine study evaluating
atogepant (QULIPTATM) in adult patients that met primary
endpoint of statistically significant reduction from baseline in
mean monthly migraine days compared to placebo
- If approved, atogepant
(QULIPTA) would be the first gepant (oral calcitonin gene-related
peptide [CGRP] receptor antagonist) with a broad preventive
treatment of migraine indication that expands treatment to patients
with chronic migraine
- Label expansion would
make AbbVie the only company to offer two preventive treatments for
those with chronic migraine, atogepant (QULIPTA) and
onabotulinumtoxinA (BOTOX®)
NORTH
CHICAGO, Ill., June 21,
2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced that it has submitted a supplemental New Drug Application
(sNDA) for atogepant (QULIPTATM) to the U.S. Food and
Drug Administration (FDA) to support the preventive treatment of
chronic migraine in adults. If approved, atogepant (QULIPTA) would
be the first gepant (oral calcitonin gene-related peptide [CGRP]
receptor antagonist) approved for the broad indication of the
preventive treatment of migraine, including episodic and chronic.
The sNDA submission includes data from the pivotal Phase 3 PROGRESS
trial in patients with chronic migraine, which supplements the
existing data in episodic migraine. People living with chronic
migraine experience headaches for 15 or more days per month, which,
on at least eight of those days per month, have the features of
migraine.1
"Having one oral medication to treat both episodic and chronic
migraine would be an important advancement for health care
providers and patients," said Michael
Gold, M.D., therapeutic area head, neuroscience development,
AbbVie. "This sNDA approval would also diversify AbbVie's migraine
portfolio and make it the only company to offer two approved
preventive treatments for those living with chronic migraine. No
two migraine patients are alike, so having multiple treatment
options with unique mechanisms of action is critical."
The pivotal Phase 3 PROGRESS trial met its primary endpoint of
statistically significant reduction from baseline in mean monthly
migraine days compared to placebo across the 12-week treatment
period in adults with chronic migraine. 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 six
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.
The overall safety profile of the Phase 3 PROGRESS study was
consistent with safety findings observed in previous studies in an
episodic migraine population. The most common adverse events were
constipation and nausea.
Atogepant is marketed as QULIPTATM in the United States and is FDA-approved to treat
adults with episodic migraine. Use of atogepant for the preventive
treatment of chronic migraine in the
United States is not approved, and its safety and efficacy
have not been evaluated by regulatory authorities.
About the Phase 3 PROGRESS Clinical Trial
The Phase 3 PROGRESS clinical trial evaluated the safety,
tolerability and efficacy of oral atogepant for the preventive
treatment of chronic migraine.2 The patient population
for the study included patients with a diagnosis of chronic
migraine for at least one year, and greater than or equal to 15
headache days with greater than or equal to eight migraine days in
the 28 days prior to randomization.2 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.2
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 QULIPTA™ (atogepant)
QULIPTA™ was approved by the U.S. Food and Drug Administration
(FDA) for the preventive treatment of episodic migraine in adults
in September 2021. It is available in
the United States as the first and
only gepant (oral calcitonin gene-related peptide [CGRP] receptor
antagonist) developed specifically for the preventive treatment of
migraine and is now under review by the FDA to expand the episodic
indication to also treat patients with chronic migraine. CGRP and
its receptors are expressed in regions of the nervous system
associated with migraine pathophysiology, and studies have shown
that CGRP levels are elevated during migraine attacks. QULIPTA
blocks CGRP through a once-daily dose and is available in three
strengths – 10 mg, 30 mg and 60 mg.
QULIPTA™ USE AND U.S. IMPORTANT SAFETY INFORMATION
QULIPTA is a prescription medicine used for the preventive
treatment of episodic migraine in adults.
Before taking QULIPTA, tell your healthcare provider about
all your medical conditions, including if you:
- Have kidney problems or are on dialysis
- Have liver problems
- Are pregnant or plan to become pregnant. It is not known if
QULIPTA will harm your unborn baby
- Are breastfeeding or plan to breastfeed. It is not known if
QULIPTA passes into your breast milk. Talk to your healthcare
provider about the best way to feed your baby while taking
QULIPTA
Tell your healthcare provider about all the medicines you
take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements. QULIPTA may affect the way other
medicines work, and other medicines may affect how QULIPTA works.
Your healthcare provider may need to change the dose of QULIPTA
when taken with certain other medicines.
The most common side effects of QULIPTA are nausea,
constipation, and fatigue. These are not all the possible side
effects of QULIPTA.
Please see full Prescribing Information.
Globally, prescribing information varies; refer to the
individual country product label for complete information.
About BOTOX® (onabotulinumtoxinA)
BOTOX® was first approved by the FDA in 1989 for two
rare eye muscle disorders – blepharospasm and strabismus in adults.
Today, BOTOX® is FDA-approved for 12 therapeutic
indications, including chronic migraine, overactive bladder,
leakage of urine (incontinence) due to overactive bladder caused by
a neurologic condition in adults and in pediatric patients five
years of age and older, cervical dystonia, adult and pediatric
spasticity, and severe underarm sweating (axillary
hyperhidrosis).
BOTOX® (onabotulinumtoxinA) U.S.
Important Information
Indications
BOTOX® is a prescription medicine that is injected into
muscles and used:
- To treat overactive bladder symptoms such as a strong need to
urinate with leaking or wetting accidents (urge urinary
incontinence), a strong need to urinate right away (urgency), and
urinating often (frequency) in adults 18 years and older when
another type of medicine (anticholinergic) does not work well
enough or cannot be taken
- To treat leakage of urine (incontinence) in adults 18 years and
older with overactive bladder caused by a neurologic disease who
still have leakage or cannot tolerate the side effects after trying
an anticholinergic medication
- To treat overactive bladder due to a neurologic disease in
children 5 years of age and older when another type of medicine
(anticholinergic) does not work well enough or cannot be taken
- 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
- To treat increased muscle stiffness in people 2 years of age
and older with spasticity
- To treat the abnormal head position and neck pain that happens
with cervical dystonia (CD) in people 16 years and older
- To treat certain types of eye muscle problems (strabismus) or
abnormal spasm of the eyelids (blepharospasm) in people 12 years of
age and older
BOTOX® is also injected into the skin to treat the
symptoms of severe underarm sweating (severe primary axillary
hyperhidrosis) when medicines used on the skin (topical) do not
work well enough in people 18 years and 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).
BOTOX® has not been shown to help people perform
task-specific functions with their upper limbs or increase movement
in joints that are permanently fixed in position by stiff
muscles.
It is not known whether BOTOX® is safe and effective
for severe sweating anywhere other than your armpits.
U.S. 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, severe
underarm sweating, blepharospasm, or strabismus.
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 the 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.
Do not receive BOTOX® for the
treatment of urinary incontinence if you: have a urinary tract
infection (UTI) or cannot empty your bladder on your own and are
not routinely catheterizing. Due to the risk of urinary retention
(not being able to empty the bladder), only patients who are
willing and able to initiate catheterization post treatment, if
required, should be considered for treatment.
Patients treated for overactive bladder:
In clinical trials, 36 of the 552 patients had to
self-catheterize for urinary retention following treatment with
BOTOX® compared to 2 of the 542 treated with
placebo. The median duration of post-injection catheterization for
these patients treated with BOTOX® 100 Units (n = 36)
was 63 days (minimum 1 day to maximum 214 days) as compared to a
median duration of 11 days (minimum 3 days to maximum 18 days) for
patients receiving placebo (n = 2). Patients with diabetes mellitus
treated with BOTOX® were more likely to develop urinary
retention than nondiabetics.
Adult Patients treated for overactive bladder due to
neurologic disease:
In clinical trials, 30.6% of patients (33/108) who were not
using clean intermittent catheterization (CIC) prior to injection,
required catheterization for urinary retention following treatment
with BOTOX® 200 Units as compared to 6.7% of
patients (7/104) treated with placebo. The median duration of
post-injection catheterization for these patients treated with
BOTOX® 200 Units (n = 33) was 289 days (minimum 1 day to
maximum 530 days) as compared to a median duration of 358 days
(minimum 2 days to maximum 379 days) for patients receiving placebo
(n = 7). Among patients not using CIC at baseline, those with MS
were more likely to require CIC post injection than those with
SCI.
The dose of BOTOX® is not the same as,
or comparable to, another botulinum toxin product.
Serious and/or immediate allergic reactions have been
reported, including itching, rash, red itchy welts, wheezing,
asthma symptoms, 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 if you have any breathing-related
problems. Your doctor may monitor you for breathing problems
during treatment with BOTOX® for spasticity or for
detrusor overactivity associated with a neurologic condition. The
risk of developing lung disease in patients with reduced lung
function is increased in patients receiving BOTOX®.
Cornea problems have been reported. Cornea (surface of
the eye) problems have been reported in some people receiving
BOTOX® for their blepharospasm, especially in people
with certain nerve disorders. BOTOX® may cause the
eyelids to blink less, which could lead to the surface of the eye
being exposed to air more than is usual. Tell your doctor if you
experience any problems with your eyes while receiving
BOTOX®. Your doctor may treat your eyes with drops,
ointments, contact lenses, or with an eye patch.
Bleeding behind the eye has been reported. Bleeding
behind the eyeball has been reported in some people receiving
BOTOX® for their strabismus. Tell your doctor if you
notice any new visual problems while receiving
BOTOX®.
Bronchitis and upper respiratory tract infections (common
colds) have been reported. Bronchitis was reported more
frequently in adults receiving BOTOX® for upper limb
spasticity. Upper respiratory infections were also reported more
frequently in adults with prior breathing-related problems with
spasticity. In pediatric patients treated with BOTOX®
for upper limb spasticity, upper respiratory tract infections were
reported more frequently. In pediatric patients treated with
BOTOX® for lower limb spasticity, upper respiratory
tract infections were not reported more frequently than
placebo.
Autonomic dysreflexia in patients treated for overactive
bladder due to neurologic disease. Autonomic dysreflexia
associated with intradetrusor injections of BOTOX® could
occur in patients treated for detrusor overactivity associated with
a neurologic condition and may require prompt medical therapy. In
clinical trials, the incidence of autonomic dysreflexia was greater
in adult patients treated with BOTOX® 200 Units compared
with placebo (1.5% versus 0.4%, respectively).
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; have symptoms of a urinary tract infection (UTI) and
are being treated for urinary incontinence (symptoms of a urinary
tract infection may include pain or burning with urination,
frequent urination, or fever); have problems emptying your bladder
on your own and are being treated for urinary incontinence; 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 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 by injection; take muscle
relaxants; take an allergy or cold medicine; take a sleep medicine;
take aspirin-like products or blood thinners.
Other side effects of
BOTOX® include: dry mouth, discomfort or
pain at the injection site, tiredness, headache, neck pain, eye
problems: double vision, blurred vision, decreased eyesight,
drooping eyelids, swelling of your eyelids, dry eyes; drooping
eyebrows; and upper respiratory tract infection. In adults being
treated for urinary incontinence, other side effects include
urinary tract infection and painful urination. In children being
treated for urinary incontinence, other side effects include
urinary tract infection and bacteria in the urine. If you have
difficulty fully emptying your bladder on your own after receiving
BOTOX®, you may need to use disposable self-catheters to
empty your bladder up to a few times each day until your bladder is
able to start emptying again.
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 Product
Information, including Boxed Warning and Medication Guide.
Globally, prescribing information varies; refer to the
individual country product label for complete information.
If you are having difficulty paying for your medicine, AbbVie
may be able to help.
Visit AbbVie.com/myAbbVieAssist to learn more.
About Migraine and Chronic Migraine
Migraine is a complex neurological disease with recurrent
attacks that are often incapacitating and characterized by severe,
throbbing headache pain as well as compounding associated symptoms
like extreme sensitivity to light, sound or nausea.1 It
is highly prevalent, affecting more than 1 billion people
worldwide, including 39 million people in the United States alone, and is the highest
cause of disability worldwide for people under 50 years of
age.3-5
People living with chronic migraine experience headaches or
migraine for 15 or more days per month, with at least eight of
those days associated with migraine.1 Chronic migraine
impacts 1%-2% of the global population.6 It is
differentiated from episodic migraine by its more debilitating
disease profile including greater prevalence of comorbid conditions
as well as higher frequency of headache and migraine
days.7-9 Individuals with chronic migraine experience
frequent disabling migraine attacks, preventing them from
performing daily activities and significantly affecting their
quality of life. This results in substantial societal and familial
burden.10-14 Significant direct and indirect costs are
also associated with chronic migraine, leading to economic burden
for patients and healthcare systems.15-17
About AbbVie in Migraine
At AbbVie, we are committed to empowering people living with
migraine disease. We advance science that enables health care
providers to care for people impacted across the spectrum of
migraine. Through education and partnerships with the migraine
community, we strive to help those with migraine navigate barriers
to care, access effective treatments and reduce the impact of
migraine on their lives.
About AbbVie in Neuroscience
At AbbVie, our commitment to preserve the personhood of those
living with neurological and psychiatric disorders is unwavering.
Every challenge in this uncharted territory makes us more
determined and drives us harder to discover and deliver solutions
for patients, care partners and clinicians. AbbVie's Neuroscience
portfolio consists of approved therapies in neurological and
psychiatric disorders, including bipolar I disorder, cervical
dystonia, major depressive disorder, migraine, Parkinson's disease,
post-stroke spasticity, schizophrenia and others along with a
robust pipeline.
We have a strong investment in neuroscience research, with our
Foundational Neuroscience Center in Cambridge, Massachusetts, and our Neuroscience
Discovery site in Ludwigshafen, Germany, where our research and resilience in
these challenging therapeutic areas is yielding a deeper
understanding of the pathophysiology of neurological and
psychiatric disorders, and identifying targets for potential
disease-modifying therapeutics aimed at making a difference in
people's lives.
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 our
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.
1 Headache Classification Committee of the
International Headache Society (IHS) The International
Classification of Headache Disorders, 3rd edition. Cephalalgia.
2018;38:1-211.
2 Efficacy, 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 June 14, 2022.
3 The Facts About Migraine. American Migraine
Foundation. Available at:
https://americanmigrainefoundation.org/resource-library/migraine-facts/.
Accessed on February 23, 2022.
4 Navigating Life with Migraine. American Migraine
Foundation. Available at:
https://americanmigrainefoundation.org/living-with-migraine/migraine-essentials/.
Accessed on: February 23, 2022.
5 Steiner, T. J., Stovner, L. J., 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.
6 Natoli JL, Manack A, Dean B, et al. Global
prevalence of chronic migraine: a systematic review. Cephalalgia.
2010;30:599-609.
7 Katsarava Z, Buse DC, Manack AN, Lipton RB.
Defining the differences between episodic migraine and chronic
migraine. Curr Pain Headache Rep. 2012;16:86-92.
8 Buse DC, Manack A, Serrano DC, et al.
Sociodemographic and comorbidity profiles of chronic migraine and
episodic migraine sufferers. J Neurol Neurosurg Psychiatry.
2010;81:428-432.
9 Adams AM, Serrano D, Buse DC, et al. The impact
of chronic migraine: The Chronic Migraine Epidemiology and Outcomes
(CaMEO) Study methods and baseline results. Cephalalgia. 2015;35(7)
563-578.
10 Blumenfeld A, Varon S, Wilcox TK, et al.
Disability, HRQoL and resource use among chronic and episodic
migraineurs: results from the International Burden of Migraine
Study (IBMS). Cephalalgia. 2011;31:301-315.
11 Lantéri-Minet M, Duru G, Mudge M, Cottrell S.
Quality of life impairment, disability and economic burden
associated with chronic daily headache, focusing on chronic
migraine with or without medication overuse: a systematic review.
Cephalalgia. 2011;31:837-850.
12 Buse DC, Scher AI, Dodick DW, et al. Impact of
migraine on the family: perspectives of people with migraine and
their spouse/domestic partner in the CaMEO Study. Mayo Clin Proc. 2016;91:596-611.
13 Buse DC, Powers SW, Gelfand AA, et al.
Adolescent perspectives on the burden of a parent's migraine:
results from the CaMEO study. Headache. 2018;58:512-524.
14 Buse DC, Murray S, Dumas PK, et al. Life with
migraine, effect on relationships, career and finances, and overall
health and well-being results of the Chronic Migraine Epidemiology
and Outcomes (CaMEO) Study. Cephalalgia. 2018;38(Suppl 1):9-10.
15 Messali A, Sanderson JC, Blumenfeld AM, et al.
Direct and indirect costs of chronic and episodic migraine in
the United States: a web-based
survey. Headache. 2016;56:306-322.
16 Sanderson JC, Devine EB, Lipton RB, et al.
Headache-related health resource utilization in chronic and
episodic migraine across six countries. J Neurol Neurosurg
Psychiatry. 2013;84:1309-1317.
17 Blumenfeld AM, Varon SF, Wilcox TK, et al.
Disability, HRQoL and resource use among chronic and episodic
migraineurs: Results from the International Burden of Migraine
Study (IBMS). Cephalalgia. 2011;31:301-315.
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