DUBLIN, Ireland, March 8, 2017 /PRNewswire/ -- Allergan plc
(NYSE: AGN), a leading global pharmaceutical company, today
announced that the U.S. Food and Drug Administration (FDA) has
accepted for filing the company's supplemental New Drug Application
(sNDA) for VRAYLAR (cariprazine), seeking the addition of new
clinical data evaluating VRAYLAR for the maintenance of efficacy in
adults with schizophrenia to the current product label.
"Most patients with schizophrenia are at very high risk of
relapse in the absence of antipsychotic treatment," said Dr.
Herbert Meltzer, Professor of
Psychiatry at Northwestern Feinberg School of Medicine. "Without
maintenance treatment, 60–70 percent of patients relapse within one
year, and almost 90 percent relapse within two years. These new
data show that VRAYLAR may be a treatment option for the
maintenance treatment of schizophrenia."
The data included in the sNDA are from a Phase 3 multinational,
randomized, double-blind, placebo-controlled, parallel-group study
of cariprazine in adults with schizophrenia (RG-MD-06), which found
cariprazine compared to placebo significantly delayed the time to
relapse (p=.0010, hazard ratio [HR]: 0.45 [95% CI: 0.28,
0.73]). 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 to
continue their cariprazine dose (3, 6 or 9 mg per day) or switched
to placebo for up to 72 weeks or until a relapse occurred. The
primary endpoint was time to first symptom relapse during the
double blind phase.
Relapse occurred in nearly twice as many placebo- (47.5%) as
cariprazine-treated (24.8%) patients. At the end of the
double-blind treatment period, analysis of exploratory endpoints
also showed a greater mean worsening of symptoms in placebo- vs
cariprazine-treated patients on all efficacy parameters as measured
by Positive and Negative Syndrome Scale (PANSS) total and subscale
scores, the Clinical Global Impressions-Severity (CGI-S) rating
scale, the 16-Item Negative Symptom Assessment (NSA-16) and the
Personal and Social Performance Scale (PSP) total score. The safety
results were consistent with the profile observed to date for
cariprazine; no new safety concerns were observed.
"These Phase 3 data offer additional information about the
long-term efficacy and safety of VRAYLAR for the maintenance
treatment of schizophrenia," said David
Nicholson, President and EVP, Global R&D at Allergan.
"This sNDA filing is part of our commitment to mental health, and
we continue to pursue research that will provide physicians and
patients with comprehensive information needed to make educated
choices regarding treatment options."
Cariprazine was approved by the FDA in September
2015 and is marketed as VRAYLAR™ in the US for the acute
treatment of manic or mixed episodes of Bipolar I Disorder and the
treatment of Schizophrenia in adults.
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 at dopamine D3, dopamine
D2, and with high binding affinity at the serotonin
5-HT1A. 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 on this once daily
option for the acute treatment of manic or mixed episodes
associated with bipolar I disorder and for the treatment of
schizophrenia in adults.
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
pharmaceuticals, devices and biologic 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, the Company's
R&D model, which defines our approach to identifying and
developing game-changing ideas and innovation for better patient
care. This approach has led to Allergan building one of the
broadest development pipelines in the pharmaceutical industry with
70+ mid-to-late stage pipeline programs in development.
Our Company's success is powered by our more than 16,000 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 of existing trends and
information as of the date of this release. Except as expressly
required by law, Allergan disclaims any intent or obligation to
update these forward-looking statements. 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. Except as expressly required by law, Allergan
disclaims any intent or obligation to update these forward-looking
statements.
ALLERGAN CONTACTS:
Investors:
Lisa De
Francesco
(862) 261-7152
Karina Calzadilla
(862) 261-7328
Media:
Mark Marmur
(862) 261-7558
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SOURCE Allergan plc