- Approval marks fourth indication for VRAYLAR, backed
by proven efficacy and well-established tolerability as an
adjunctive treatment for major depressive disorder (MDD) with an
antidepressant therapy (ADT), showing improvement in symptoms when
compared to placebo + ADT
- Designed for specific mood disorders, VRAYLAR is now
the first and only dopamine and serotonin partial agonist
FDA-approved for the most common forms of depression – as an
adjunctive treatment for MDD and the treatment of depressive
episodes associated with bipolar I disorder
- About one in five U.S. adults will experience MDD
during their lifetime, and many of them may have partial response
to the treatment with an ADT
NORTH
CHICAGO, Ill., Dec. 16,
2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced that the U.S. Food and Drug Administration (FDA) has
approved VRAYLAR® (cariprazine) as an adjunctive therapy
to antidepressants for the treatment of major depressive disorder
(MDD) in adults. Supported by clinical data demonstrating efficacy
and well-established tolerability, this additional indication
provides a new option for adults who have a partial response to the
treatment of an antidepressant.
Experience the interactive Multimedia News Release here:
https://www.multivu.com/players/English/9107351-vraylar-cariprazine-fda-approval-major-depressive-disorder/
"Many living with major depressive disorder find that their
ongoing antidepressant therapy doesn't offer meaningful relief from
the symptoms they experience every day," said Thomas Hudson, M.D., senior vice president,
research and development, chief scientific officer, AbbVie.
"Today's approval of VRAYLAR provides an important new treatment
option to meet a critical unmet medical need. AbbVie is committed
to driving progress and advancing solutions for patients living
with complex neuropsychiatric conditions."
MDD is one of the most common mental disorders in the U.S.;
approximately one in five adults will experience this disorder
during their lifetime.1 In a large U.S. study of adults
with MDD, approximately 50 percent still had depressive symptoms
with their first antidepressant.2 If some symptoms of
depression persist while on an antidepressant, adding a different
type of medication, often referred to as an adjunctive treatment,
to the existing regimen may help.
"Patients with inadequate response to standard antidepressant
medication are often frustrated by the experience of trying
multiple medicines and still suffering from unresolved symptoms.
Instead of starting over with another standard antidepressant,
VRAYLAR works with an existing treatment and can help build on the
progress already made," said Gary
Sachs, MD, clinical vice president at Signant Health,
associate clinical professor of psychiatry at Massachusetts General
Hospital, and lead Phase 3 clinical trial investigator. "For adults
living with major depressive disorder, because of inadequate
improvement in response to standard antidepressants, VRAYLAR is an
efficacious adjunctive treatment option with a well-characterized
safety profile."
Cariprazine is marketed as VRAYLAR® in the U.S., and
in addition to being approved as an adjunctive therapy to
antidepressants for the treatment of MDD in adults, it is
FDA-approved to treat adults with depressive, acute manic and mixed
episodes associated with bipolar I disorder, as well as
schizophrenia. Cariprazine is 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.
"When we were in the early stages of development for
cariprazine, we focused on designing a compound that covers a range
of symptoms for mental health conditions and affects the dopamine
D3 receptor," said István Greiner, Ph.D., research and development,
director, Gedeon Richter. "While
schizophrenia and bipolar manic and mixed episodes were the first
indications in the U.S. market, we are thrilled to see the full
potential of cariprazine unlocked with approvals in bipolar I
depression, and now, as an antidepressant adjunct in major
depressive disorder."
Highlights from the clinical program supporting the approval
include:
- A Phase 3 Study 3111-301-001 showed a clinically and
statistically significant change from baseline to week six in the
Montgomery-Åsberg Depression
Rating Scale (MADRS) total score for patients treated with
cariprazine at 1.5 mg/day + ADT compared with placebo + ADT. A
second registration-enabling study, RGH-MD-75, showed a clinically
and statistically significant change from baseline to week eight in
the MADRS total score for patients treated with cariprazine at
2-4.5 mg/day (mean dose 2.6 mg) + ADT compared with placebo +
ADT.
- Cariprazine was generally well tolerated in 6- and 8-week
studies. Mean weight change was < 2lbs and ≤ 3% of patients had
a weight increase of ≥ 7%.
- The starting dosage of VRAYLAR is 1.5 mg once daily. Depending
upon clinical response and tolerability, the dosage can be
increased to 3 mg once daily on Day 15. In clinical trials, dosage
titration at intervals of less than 14 days resulted in a higher
incidence of adverse reactions. The maximum recommended dosage is 3
mg once daily.
- Most common adverse reactions observed in the adjunctive MDD
studies (≥ 5% and at least twice the rate of placebo) were:
-
- Akathisia, nausea, and insomnia at the recommended doses in
6-week, fixed-dose trials
- Akathisia, restlessness, fatigue, constipation, nausea,
increased appetite, dizziness, insomnia, and extrapyramidal
symptoms in one 8-week flexible-dose trial at a titration of less
than 14 days
About Major Depressive Disorder (MDD)
MDD is one of
the most common mental disorders in the U.S., characterized by
symptoms such as overwhelming feelings of sadness and/or loss of
interest that don't go away after two weeks.3 MDD can
cause severe functional impairment, adversely affect interpersonal
relationships, and may impact the quality of life.4 It
is a leading cause of disability in the world,5 and has
a lifetime prevalence of 20% for adults in the U.S.1
Symptoms can include depressed mood, loss of pleasure or interest
in activities, feelings of worthlessness, lack of energy, poor
concentration, appetite changes, sleep disturbances, suicidal
thoughts, and feeling restless or moving or talking more
slowly.3 In the U.S., the estimated economic
burden of MDD has been estimated to be around $326 billion in
2020.6
About Study 3111-301-001
Study 3111-301-001 is a
randomized, double-blind, placebo-controlled, multicenter trial
with 751 participants conducted in the
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. Patients treated with cariprazine 3.0 mg/day + ADT
demonstrated improvement in MADRS total score at week six over
placebo + ADT but did not meet statistical significance.
About Study RGH-MD-75
Study RGH-MD-75 is a randomized,
double-blind, placebo-controlled, flexible-dose, outpatient,
multicenter trial with 808 participants, conducted in the United States, Estonia, Finland, Slovakia, Ukraine and Sweden. After 7-14 days of screening and
washout of prohibited medications, eligible patients entered an
8-week, double-blind treatment period in which they continued
antidepressant treatment and were randomized (1:1:1) to adjunctive
cariprazine 1-2 mg/day, cariprazine 2-4.5 mg/day, or placebo. Data
from Study RGH-MD-75 were published in the Journal of Clinical
Psychiatry.7 Patients treated with cariprazine 1-2
mg/day + ADT demonstrated improvement in MADRS total score at week
eight over placebo + ADT but did not meet statistical
significance.
About VRAYLAR® (cariprazine)
VRAYLAR
is an oral, once-daily atypical antipsychotic approved as an
adjunctive therapy to antidepressants for the treatment of major
depressive disorder (MDD) in adults (1.5 or 3 mg/day), 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).
While the mechanism of action of VRAYLAR is unknown, the
efficacy of VRAYLAR is thought to 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.8 The
clinical significance of these in vitro data is
unknown.
VRAYLAR is 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).
Visit www.vraylar.com for more information.
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)
- along with antidepressant medicines to treat major depressive
disorder
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.
VRAYLAR and antidepressants may increase suicidal thoughts or
actions in some children and young adults especially within the
first few months of treatment or when the dose is changed.
Depression and other 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 VRAYLAR or the
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)
- Sleepiness, drowsiness, feeling tired, difficulty thinking
and doing normal activities: 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. Taking VRAYLAR during your third trimester of
pregnancy may cause your baby to have abnormal muscle movements or
withdrawal symptoms after birth. 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 include
difficulty moving or slow movements, tremors, uncontrolled body
movements, restlessness and feeling like you need to move around,
sleepiness, nausea, vomiting, indigestion, constipation, feeling
tired, trouble sleeping, increased appetite, and dizziness.
These are not all the
possible side effects of VRAYLAR.
Please see the full Prescribing
Information, including Boxed Warnings,
and Medication Guide.
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.
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.
US-VRAA-220055
References:
- Hasin DS, Sarvet AL, Meyers JL, et al. Epidemiology of Adult
DSM-5 Major Depressive Disorder and Its Specifiers in the United States. JAMA Psychiatry.
2018;75(4):336-346.
- Trivedi MH, Rush AJ, Wisniewski SR, et al. Am J
Psychiatry. 2006;163(1):28-40.
- National Institute of Mental Health (2022). Depression.
Available at: https://www.nimh.nih.gov/health/topics/depression.
Accessed December 2022.
- Bains N, Abdijadid S. Major Depressive Disorder. [Updated 2022
Jun 1]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls
Publishing; 2022 Jan-. Available at:
https://www.ncbi.nlm.nih.gov/books/NBK559078/. Accessed
December 2022.
- Friedrich MJ. Depression Is the Leading Cause of Disability
Around the World. JAMA. 2017;317(15):1517.
- Greenberg P, Fournier AA, Sistsky T, et
al. Pharmacoeconomics. 2021;39(6):653-65.
- Durgam S, Earley W, Guo H, et al. J Clin Psychiatry.
2016;77(3):371-8.
- VRAYLAR. Package insert. Allergan USA, Inc; 2022.
Contacts
US Media
Mary Byun
+1 (646) 709-4409
mary.byun@abbvie.com
Global Media
Mabel Martinez
+1 (224) 306-4412
mabel.martinez@abbvie.com
Investors
Liz Shea
+1 (847) 935-2211
liz.shea@abbvie.com
View original
content:https://www.prnewswire.com/news-releases/us-fda-approves-vraylar-cariprazine-as-an-adjunctive-treatment-for-major-depressive-disorder-301705552.html
SOURCE AbbVie