- In Study 3111-301-001, cariprazine
(VRAYLAR®; 1.5mg/day) achieved the primary
endpoint of statistically significant improvement on the
Montgomery-Åsberg
Depression Rating Scale (MADRS) total score in patients with major
depressive disorder (MDD) with an inadequate response to ongoing
antidepressant therapy
- Safety profile was consistent with that of previous studies
across indications in the treatment of adults with depressive
episodes associated with bipolar I disorder, the acute
treatment of manic or mixed episodes associated with bipolar I
disorder and schizophrenia
- AbbVie's supplemental New Drug Application (sNDA) for
cariprazine, which includes Study 3111-301-001, is currently
under review by the U.S. Food and Drug Administration (FDA) for
expanded use in the adjunctive treatment of MDD with a decision
expected by year-end
NORTH
CHICAGO, Ill., May 23, 2022
/PRNewswire/ -- AbbVie (NYSE: ABBV) today announced it will present
positive data from a Phase 3 trial of cariprazine
(VRAYLAR®; 1.5mg/day), Study 3111-301-001, for the
adjunctive treatment of major depressive disorder (MDD) in patients
with an inadequate response to ongoing antidepressant therapy. The
study met its primary endpoint of statistically significant
improvement using the Montgomery-Åsberg Depression Rating Scale
(MADRS) total score in patients compared with placebo. These
results will be presented (Poster Number: P7-037) on Tuesday, May 24, at the American Psychiatric
Association (APA) Annual Meeting in New
Orleans.
AbbVie's supplemental New Drug Application (sNDA) for
cariprazine was supported by two positive registration-enabling
studies, of which one was Study 3111-301-001. The sNDA is currently
under review by the U.S. Food and Drug Administration (FDA) for
expanded use in the adjunctive treatment of MDD with a decision
expected by year-end.
"We are pleased to present these data demonstrating
cariprazine's potential to have an impact on patients as an
adjunctive treatment of major depressive disorder,"
said Michael Gold, M.D., therapeutic area head, neuroscience
development, AbbVie. "The results from this study, along
with previously reported data, served as the basis of our recent
sNDA submission to the FDA and further underpin AbbVie's commitment
to advancing innovative psychiatric therapies for patients in
need."
The Phase 3 study showed a statistically significant change from
baseline to week six in the MADRS total score for patients treated
with cariprazine at 1.5 mg/day compared with placebo (p-value =
0.0050). Patients treated with cariprazine at 3.0 mg/day
demonstrated improvement in MADRS total score at week six compared
to placebo but did not meet statistical significance
(p-value=0.0727).
In this study, the safety data was consistent with
the established safety profile of cariprazine across
indications. There were no deaths in the trial, with serious
adverse events (SAE) occurring in both treatment (two SAEs) and
placebo (two SAEs) groups. The most common adverse events (AE) in
the treatment group were akathisia and nausea (≥5%).
"The Phase 3 trial results, along with previous study results,
indicate that cariprazine may have the potential to help patients
with MDD for whom antidepressant therapy alone is not sufficient,"
said Gary Sachs, MD, associate
clinical professor of psychiatry at Massachusetts General Hospital
and lead author of the study. "Nearly half of patients with MDD do
not experience satisfactory results from their current treatment
regimen, so ongoing research to bring more options to patients is
critical."
Cariprazine is marketed as VRAYLAR® in
the United States and is
FDA-approved to treat adults with depressive, acute manic and mixed
episodes associated with bipolar I disorder, as well as
schizophrenia. Cariprazine is being co-developed by AbbVie and
Gedeon Richter Plc. More than 8,000 patients worldwide have been
treated with cariprazine across more than 20 clinical trials
evaluating the efficacy and safety of cariprazine for a broad range
of psychiatric disorders.
About Major Depressive Disorder (MDD)
MDD is one of the most common mental disorders in the United States. In 2020, an estimated 21
million adults had at least one major depressive episode. For some
individuals, MDD can result in severe impairment which may
interfere with or limit one's daily activities.1 The
World Health Organization lists depression as the third-leading
cause of disability worldwide and as a major contributor to the
overall global burden of disease. Symptoms can include depressed
mood, loss of pleasure or interest in activities, changes in
appetite or weight, changes in sleep, psychomotor retardation, loss
of energy, feelings of worthlessness, indecisiveness, and recurrent
thoughts of death.2 In the
United States, the economic burden of MDD has been estimated
to be around $326
billion.3
About Study 3111-301-001
Study 3111-301-001 is a randomized, double-blind,
placebo-controlled, multicenter trial with 751 participants
conducted in United States,
Bulgaria, Estonia, Germany, Hungary, Ukraine and the United Kingdom. Following a screening period
of up to 14 days, patients with an inadequate clinical response to
their antidepressant monotherapy (ADT) were randomized into three
treatment groups (1:1:1). The first group received cariprazine 1.5
mg/day + ADT, the second group received cariprazine 3.0 mg/day +
ADT, and the third group received placebo + ADT. For six weeks, the
medication was given once daily in addition to the ongoing ADT
treatment.
The primary endpoint was determined using the MADRS total score,
a 10-item, clinician-rated scale that evaluates the patient's
depressive symptomatology during the past week. Patients are rated
on items assessing feelings of sadness, lassitude, pessimism, inner
tension, suicidality, reduced sleep or appetite, difficulty in
concentration, and lack of interest. Each item is scored on a
7-point scale with a score of 0 reflecting no symptoms and a score
of 6 reflecting symptoms of maximum severity.4
More information can be found on
www.clinicaltrials.gov (NCT03738215).
About VRAYLAR® (cariprazine)
VRAYLAR is an oral, once-daily atypical antipsychotic approved
for the treatment of depressive episodes associated with bipolar I
disorder (bipolar depression) in adults (1.5 or 3 mg/day) and for
the acute treatment of adults with manic or mixed episodes
associated with bipolar I disorder (3 to 6 mg/day). VRAYLAR is also
approved for the treatment of schizophrenia in adults (1.5 to 6
mg/day). Use of VRAYLAR in adjunctive treatment of major depressive
disorder is not approved and its safety and efficacy have not been
evaluated by regulatory authorities.
While the mechanism of action of VRAYLAR is unknown, the
efficacy of VRAYLAR could be mediated through a combination of
partial agonist activity at central dopamine D₂ and serotonin
5-HT1A receptors and antagonist activity at
serotonin 5-HT2A receptors. Pharmacodynamic studies
with VRAYLAR have shown that it may act as a partial agonist with
high binding affinity at dopamine D3, dopamine
D2, and serotonin 5-HT1A receptors.
VRAYLAR demonstrated up to ~8-fold greater in
vitro affinity for dopamine D3 vs
D2 receptors. VRAYLAR also acts as an antagonist at
serotonin 5-HT2B and
5-HT2A receptors with high and moderate binding
affinity, respectively as well as it binds to the histamine
H1 receptors. VRAYLAR shows lower binding affinity
to the serotonin 5-HT2C and α1A-
adrenergic receptors and has no appreciable affinity for
cholinergic muscarinic receptors.5 The clinical
significance of these in vitro data is
unknown.
VRAYLAR is being developed jointly by AbbVie and Gedeon
Richter Plc, with AbbVie responsible for commercialization in the
U.S., Canada, Japan,
Taiwan and certain Latin American
countries (including Argentina,
Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, Peru
and Venezuela).
VRAYLAR® (cariprazine) Uses and
Important Safety Information
VRAYLAR is a prescription medicine used in adults:
- to treat schizophrenia
- for short-term (acute) treatment of manic or mixed episodes
that happen with bipolar I disorder
- to treat depressive episodes that happen with bipolar I
disorder (bipolar depression)
What is the most important information I
should know about VRAYLAR?
Elderly people with dementia-related psychosis (having lost touch with reality due to confusion and
memory loss) taking medicines like VRAYLAR are
at an increased risk of death. VRAYLAR is not approved
for treating patients
with dementia-related psychosis.
Antidepressants may increase suicidal thoughts or actions in
some children and young adults within the first few months of
treatment and when the dose is changed. Depression and other
serious mental illnesses are the most important causes of suicidal
thoughts and actions. Patients on antidepressants and their
families or caregivers should watch for new or worsening depression
symptoms, especially sudden changes in mood, behaviors, thoughts,
or feelings. This is very important when an antidepressant is
started or when the dose is changed. Report any change in these
symptoms immediately to the doctor.
VRAYLAR may cause serious side effects, including:
- Stroke (cerebrovascular
problems) in elderly people with dementia-related
psychosis that can lead to death
-
Neuroleptic malignant syndrome
(NMS): Call your healthcare provider or go to
the nearest hospital emergency
room right away if you have high
fever, stiff muscles, confusion, increased sweating,
or changes in breathing, heart rate, and
blood pressure. These can be symptoms of
a rare but potentially fatal side
effect called NMS. VRAYLAR should be stopped if
you have NMS
- Uncontrolled body movements
(tardive dyskinesia or
TD): VRAYLAR may cause movements that you cannot control
in your face, tongue, or other body parts. Tardive dyskinesia may
not go away, even if you stop taking VRAYLAR. Tardive dyskinesia
may also start after you stop taking VRAYLAR
- Late-occurring side effects: VRAYLAR stays in your
body for a long time. Some side effects may not happen right away
and can start a few weeks after starting VRAYLAR, or if your dose
increases. Your healthcare provider should monitor you for side
effects for several weeks after starting or increasing dose of
VRAYLAR
- Problems with your metabolism, such as:
-
- High blood sugar and diabetes: Increases in blood sugar
can happen in some people who take VRAYLAR. Extremely high blood
sugar can lead to coma or death. Your healthcare provider should
check your blood sugar before or soon after starting VRAYLAR and
regularly during treatment. Tell your healthcare provider if you
have symptoms such as feeling very thirsty, very hungry, or sick to
your stomach, urinating more than usual, feeling weak, tired,
confused, or your breath smells fruity
- Increased fat levels
(cholesterol and triglycerides) in your
blood: Your healthcare provider should
check fat levels in your blood before or soon
after starting VRAYLAR and during treatment
- Weight gain: Weight gain
has been reported with VRAYLAR. You and your
healthcare provider should check your weight
before and regularly during treatment
- Low white blood cell
count: Low white blood cell counts have been reported with antipsychotic
drugs, including VRAYLAR. This may increase your
risk of infection. Very low white blood cell
counts, which can be fatal, have been
reported with other antipsychotics. Your healthcare provider
may do blood tests during the first few months of treatment with
VRAYLAR
- Decreased blood pressure (orthostatic
hypotension): You may feel lightheaded or
faint when you rise too quickly
from a sitting or lying position
- Falls: VRAYLAR may make you sleepy or dizzy, may cause a
decrease in blood pressure when changing position (orthostatic
hypotension), and can slow thinking and motor skills, which may
lead to falls that can cause fractures or other injuries
- Seizures
(convulsions)
-
Impaired judgment, thinking, and motor skills: Do NOT drive,
operate machinery, or do other dangerous
activities until you know how VRAYLAR
affects you. VRAYLAR may make you drowsy
- Increased body temperature: Do not become too hot or
dehydrated during VRAYLAR treatment. Do not exercise too much. In
hot weather, stay inside in a cool place if possible. Stay out of
the sun. Do not wear too much clothing or heavy clothing. Drink
plenty of water
- Difficulty swallowing that can cause food or liquid
to get into your lungs
Who should not take VRAYLAR?
Do not take VRAYLAR
if you are allergic to any of its ingredients.
Get emergency medical help if you are having an
allergic reaction (eg, rash,
itching, hives, swelling of
the tongue, lip, face or throat).
What should I tell my
healthcare provider before taking VRAYLAR?
Tell your
healthcare provider about any medical
conditions and if you:
- have or have had heart problems or a stroke
- have or have had low or high blood pressure
- have or have had diabetes or high blood sugar in you or your
family
- have or have had high levels of total cholesterol,
LDL-cholesterol, or triglycerides; or
low levels of HDL-cholesterol
- have or have had seizures (convulsions)
- have or have had kidney or liver problems
- have or have had low white blood cell count
- are pregnant or plan to become pregnant. VRAYLAR may harm your
unborn baby. Talk to your healthcare provider about the risk to
your unborn baby if you take VRAYLAR during pregnancy. If you
become pregnant or think you are pregnant during treatment, talk to
your healthcare provider about registering with the National
Pregnancy Registry for Atypical Antipsychotics
at 1-866-961-2388 or http://www.womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/
- are breastfeeding or plan to breastfeed. It is not known if
VRAYLAR passes into breast milk. Talk to your healthcare provider
about the best way to feed your baby during treatment with
VRAYLAR
Tell your
healthcare provider about all medicines that you take,
including
prescriptions, over-the-counter medicines, vitamins,
and supplements.
VRAYLAR may affect the way other medicines
work, and other medicines may affect how
VRAYLAR works. Do not start or stop any medicines while taking
VRAYLAR without talking to your healthcare provider.
What are the most common side effects of
VRAYLAR?
- The most common side effects were difficulty moving or slow
movements, tremors, uncontrolled body movements, restlessness and
feeling like you need to move around, sleepiness, nausea, vomiting,
and indigestion.
These are not all
possible side effects of VRAYLAR.
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.
If you are having difficulty paying for your medicine, AbbVie
may be able to help. Visit AbbVie.com/myAbbVieAssist to learn
more.
Please see the full Prescribing Information, including
Boxed Warnings, and Medication Guide.
Globally, prescribing information varies; refer to the
individual country product label for complete information.
About AbbVie in Mental Health
AbbVie is driving the pursuit of better mental health. Over the
last 30 years, the company's scientists and clinicians have worked
to tackle the complexity of mental illness and today offer a
portfolio of medicines and a pipeline of innovation that spans
depression, anxiety, bipolar I disorder, and schizophrenia. To
learn more about AbbVie's work to support individuals throughout
their mental health journey, please visit www.abbvie.com or follow
@abbvie on Twitter, Facebook, Instagram, YouTube
and LinkedIn.
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.
References:
- Substance Abuse and Mental Health Services Administration.
Key substance use and mental health indicators in the
United States: Results from the
2020 National Survey on Drug Use and Health. Center for
Behavioral Health Statistics and Quality.
2021. https://www.samhsa.gov/data/. Accessed February 1,
2022.
- World Health Organization. Depression. Fact Sheet. 2021.
Available at:
https://www.who.int/news-room/fact-sheets/detail/depression.
Accessed February 1, 2022.
- Greenberg P, Fournier AA, Sistsky T, et
al. Pharmacoeconomics. 2021;39(6):653-65.
- Quilty LC, Robinson JJ, Rolland JP, Fruyt FD, Rouillon F, Bagby
RM. The structure of the Montgomery-Åsberg depression rating scale over
the course of treatment for depression. Int J Methods
Psychiatr Res. 2013;22(3):175-184. doi:10.1002/mpr.1388
- AbbVie. VRAYLAR (cariprazine) [package insert]. U.S. Food and
Drug
Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204370s006lbl.pdf.
Revised January 2019. Accessed February 15, 2022.
SOURCE AbbVie
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SOURCE AbbVie