DUBLIN, Nov. 13, 2017 /PRNewswire/ -- Allergan plc
(NYSE: AGN) today announced that the U.S. Food and Drug
Administration (FDA) has approved the supplemental New Drug
Application (sNDA) for VRAYLAR™ (cariprazine) for the
maintenance treatment of adults with schizophrenia. VRAYLAR is also
approved in the U.S. in adults for the acute treatment of
schizophrenia and acute treatment of manic or mixed episodes of
bipolar I disorder.1
"Schizophrenia is one of the most challenging mental health
disorders to manage – particularly due to the complexity of patient
symptoms, varying response to treatment and high rates of relapse,"
said Dr. Herbert Meltzer, Professor
of Psychiatry and Behavioral Sciences at Northwestern Feinberg
School of Medicine. "The goal of clinicians is to minimize
relapses, which can cause significant personal distress, and can
often have serious implications for a patient's health. The
approval of VRAYLAR for the maintenance treatment of schizophrenia
provides an important therapy for patients and physicians who are
in need of long-term treatment options."
Without maintenance treatment, 60 – 70 percent of schizophrenia
patients relapse within one year. Once a schizophrenia patient
reaches the stable or maintenance phase of treatment, it is
important for the physician to develop a long-term treatment
management plan to minimize relapse risk, monitor for and reduce
severity of side effects, and address residual symptoms where
possible.2
The efficacy of VRAYLAR in the maintenance treatment of
schizophrenia was based on an up to 72-week, multinational,
double-blind, placebo-controlled, randomized withdrawal study in
the prevention of relapse in adult patients with schizophrenia. The
study included a 20-week open-label phase where patients with
schizophrenia were treated with cariprazine 3, 6 or 9 mg per day.
Patients who responded and met the stabilization criteria during
the open-label period were then randomized either to continue their
VRAYLAR dose (3, 6 or 9 mg per day) or be switched to placebo for
up to 72 weeks or until a relapse occurred. The primary endpoint
was time to relapse during the randomized, double blind
phase.1
The study demonstrated that VRAYLAR y
significantly delayed the time to relapse compared to placebo
(P=0.0010). Relapse occurred in nearly twice as many
placebo-treated patients (49.5%, n=49/99) as VRAYLAR-treated
(29.7%, n=30/101) patients. The safety results were consistent with
the profile observed to-date for VRAYLAR.1
"The differences in how people with schizophrenia respond to
treatment underscores the importance of having additional treatment
options," said David Nicholson,
Chief Research & Development Officer at Allergan. "We are
pleased that the FDA has recognized the benefits of VRAYLAR for
maintenance treatment of adults with schizophrenia. This approval
demonstrates our continued investment in VRAYLAR, as well as our
commitment to developing treatments that address unmet needs facing
people living with mental illness."
About Schizophrenia
Schizophrenia is a chronic and disabling disorder that affects
about 2.4 million American adults.3 It imposes
significant burden on patients, their families and society.
Symptoms fall into three broad categories: positive symptoms
(hallucinations, delusions, thought disorders and movement
disorders), negative symptoms (such as loss of motivation and
social withdrawal) and cognitive symptoms (problems with executive
functioning, focusing and working memory).4
About VRAYLAR™ (cariprazine)
VRAYLAR is an oral, once daily atypical antipsychotic approved
for the acute treatment of adult patients with manic or mixed
episodes associated with bipolar I disorder, with a recommended
dose range of 3 to 6 mg/day, and for the treatment of schizophrenia
in adults, with a recommended dose range of 1.5 to 6 mg/day.
While the mechanism of action of VRAYLAR in schizophrenia and
bipolar I disorder 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 cariprazine have shown that it acts as
a partial agonist with high binding affinity at dopamine
D3, dopamine D2, and serotonin
5-HT1A receptors. Cariprazine demonstrated up to ~8-fold
greater in vitro affinity for dopamine D3 vs
D2 receptors. Cariprazine 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. Cariprazine shows
lower binding affinity to the serotonin 5-HT2C and
α1A- adrenergic receptors and has no appreciable
affinity for cholinergic muscarinic receptors. The clinical
significance of these in vitro data is unknown.
VRAYLAR was discovered and co-developed by Gedeon Richter Plc
and is licensed to Actavis, now Allergan, in the U.S. and
Canada.
Visit www.VRAYLAR.com for more information.
IMPORTANT SAFETY INFORMATION
WARNING: INCREASED
MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED
PSYCHOSIS
Elderly patients
with dementia-related psychosis treated with antipsychotic drugs
are at an increased risk of death. VRAYLAR is not approved for
treatment of patients with dementia-related
psychosis
|
Contraindication: VRAYLAR is contraindicated in patients
with known hypersensitivity. Reactions have included rash,
pruritus, urticaria, and events suggestive of angioedema.
Cerebrovascular Adverse Reactions, Including Stroke: In
clinical trials with antipsychotic drugs, elderly subjects with
dementia had a higher incidence of cerebrovascular adverse
reactions, including fatalities vs placebo. VRAYLAR is not approved
for the treatment of patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): NMS, a potentially
fatal symptom complex, has been reported with antipsychotic drugs.
NMS may cause hyperpyrexia, muscle rigidity, delirium, and
autonomic instability. Additional signs may include elevated
creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute
renal failure. Manage with immediate discontinuation,
intensive symptomatic treatment, and monitoring.
Tardive Dyskinesia (TD): Risk of developing TD (a
syndrome of potentially irreversible, involuntary, dyskinetic
movements) and the likelihood it will become irreversible may
increase with the duration of treatment and the cumulative dose.
The syndrome can develop after a relatively brief treatment period,
even at low doses, or after treatment discontinuation. If signs and
symptoms of TD appear, drug discontinuation should be
considered.
Late-Occurring Adverse Reactions: Adverse events may
first appear several weeks after initiation of VRAYLAR, probably
because plasma levels of cariprazine and its major metabolites
accumulate over time. As a result, the incidence of adverse
reactions in short-term trials may not reflect the rates after
longer term exposures. Monitor for adverse reactions, including
extrapyramidal symptoms (EPS) or akathisia, and patient response
for several weeks after starting VRAYLAR and after each dosage
increase. Consider reducing the dose or discontinuing the drug.
Metabolic Changes: Atypical antipsychotics have caused
metabolic changes, such as:
- Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in
some cases associated with ketoacidosis, hyperosmolar coma, or
death, has been reported in patients treated with atypical
antipsychotics. Assess fasting glucose before or soon after
initiation of treatment, and monitor periodically during long-term
treatment.
- Dyslipidemia: Atypical antipsychotics cause adverse
alterations in lipids. Before or soon after starting an
antipsychotic, obtain baseline fasting lipid profile and monitor
periodically during treatment.
- Weight Gain: Weight gain has been observed with VRAYLAR.
Monitor weight at baseline and frequently thereafter.
Leukopenia, Neutropenia, and Agranulocytosis:
Leukopenia/neutropenia have been reported with antipsychotics,
including VRAYLAR. Agranulocytosis (including fatal cases) has been
reported with other antipsychotics. Monitor complete blood count in
patients with pre-existing low white blood cell count
(WBC)/absolute neutrophil count or history of drug-induced
leukopenia/neutropenia. Discontinue VRAYLAR at the first sign of a
clinically significant decline in WBC and in severely neutropenic
patients.
Orthostatic Hypotension and Syncope: Atypical
antipsychotics cause orthostatic hypotension and syncope, with the
greatest risk during initial titration and with dose increases.
Monitor orthostatic vital signs in patients predisposed to
hypotension and in those with cardiovascular/cerebrovascular
diseases.
Falls: VRAYLAR may cause somnolence, postural
hypotension, motor and sensory instability, which may lead to falls
and, consequently, fractures, or other injuries. For patients with
diseases, conditions, or medications that could exacerbate these
effects, complete fall risk assessments when initiating
antipsychotics and recurrently for patients on long-term
therapy.
Seizures: Use VRAYLAR with caution in patients with
history of seizures or with conditions that lower the seizure
threshold.
Potential for Cognitive and Motor Impairment: Somnolence
was reported with VRAYLAR. Caution patients about performing
activities requiring mental alertness (eg, operating hazardous
machinery or a motor vehicle).
Body Temperature Dysregulation: Use VRAYLAR with caution
in patients who may experience conditions that increase body
temperature (eg, strenuous exercise, extreme heat, dehydration, or
concomitant anticholinergics).
Dysphagia: Esophageal dysmotility and aspiration have
been associated with antipsychotics. Antipsychotic drugs, including
VRAYLAR, should be used cautiously in patients at risk for
aspiration.
Drug Interactions: Strong CYP3A4 inhibitors increase
VRAYLAR concentrations, so VRAYLAR dose reduction is recommended.
Concomitant use with CYP3A4 inducers is not recommended.
Adverse Reactions: In clinical trials, the most common
adverse reactions (≥5% and at least twice the rate of placebo) are
listed below:
- Schizophrenia: The incidences within the recommended dose range
(VRAYLAR 1.5 – 3 mg/day and 4.5 – 6 mg/day vs placebo) were: EPS
(15%, 19% vs 8%) and akathisia (9%, 13% vs 4%)
- Bipolar mania: The incidences within the recommended dose range
(VRAYLAR 3 – 6 mg/day vs placebo) were: EPS (26% vs 12%), akathisia
(20% vs 5%), dyspepsia (7% vs 4%), vomiting (10% vs 4%), somnolence
(7% vs 4%), and restlessness (7% vs 2%)
Please also see full Prescribing Information,
including Boxed Warning.
About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global
pharmaceutical company and a leader in a new industry model –
Growth Pharma. Allergan is focused on developing,
manufacturing and commercializing branded pharmaceutical, device,
biologic, surgical and regenerative medicine products for patients
around the world.
Allergan markets a portfolio of leading brands and best-in-class
products for the central nervous system, eye care, medical
aesthetics and dermatology, gastroenterology, women's health,
urology and anti-infective therapeutic categories.
Allergan is an industry leader in Open Science, a model of
research and development, which defines our approach to identifying
and developing game-changing ideas and innovation for better
patient care. With this approach, Allergan has built one of the
broadest development pipelines in the pharmaceutical industry with
55+ mid-to-late stage pipeline programs currently in
development.
Allergan's success is powered by our more than 18,000 global
colleagues' commitment to being Bold for Life. Together, we build
bridges, power ideas, act fast and drive results for our customers
and patients around the world by always doing what is right.
With commercial operations in approximately 100 countries,
Allergan is committed to working with physicians, healthcare
providers and patients to deliver innovative and meaningful
treatments that help people around the world live longer, healthier
lives every day.
For more information, visit Allergan's website
at www.Allergan.com.
Forward-Looking Statement
Statements contained in this press release that refer to future
events or other non-historical facts are forward-looking statements
that reflect Allergan's current perspective on existing trends and
information as of the date of this release. Actual results may
differ materially from Allergan's current expectations depending
upon a number of factors affecting Allergan's business. These
factors include, among others, the difficulty of predicting the
timing or outcome of FDA approvals or actions, if any; the impact
of competitive products and pricing; market acceptance of and
continued demand for Allergan's products; difficulties or delays in
manufacturing; and other risks and uncertainties detailed in
Allergan's periodic public filings with the Securities and Exchange
Commission, including but not limited to Allergan's Annual Report
on Form 10-K for the year ended December 31,
2016 and Allergan's Quarterly Report on Form 10-Q for the
period ended September 30, 2017.
Except as expressly required by law, Allergan disclaims any intent
or obligation to update these forward-looking statements.
References
1. VRAYLAR™ [package insert]. Irvine, CA: Allergan USA, Inc.; 2017.
2. Practice Guidelines for the Treatment of
Patients with Schizophrenia. American Psychiatric Association.
Available at:
https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/schizophrenia.pdf.
Accessed November 2017.
3. Schizophrenia. NIH Research Portfolio Online
Reporting Tools (RePORT). U.S. Department of Health & Human
Services.. Available at:
https://report.nih.gov/nihfactsheets/ViewFactSheet.aspx?csid=67.
Accessed November 2017.
4. Schizophrenia. National Institutes of Mental
Health (NIMH). Available at:
https://infocenter.nimh.nih.gov/nimh/product/Schizophrenia/TR%2015-3517.
Accessed November 2017.
CONTACTS: Allergan:
Investors:
Daphne Karydas
(862) 261-8006
Media:
Mark Marmur
(862) 261-7558
Frances DeSena
(862) 261-8820
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