Sunovion Pharmaceuticals Inc. Announces Data Showing Latuda® (lurasidone
HCl) was Associated with Low Rates of Weight and Metabolic Changes in
Patients with Depressive Episodes Associated with Bipolar I Disorder
A Similar Pattern of Metabolic Changes was Observed in Patients Who Received
LATUDA as Monotherapy or as Adjunctive Therapy to Mood Stabilizers
MARLBOROUGH, Mass. -- May 20, 2013
Sunovion Pharmaceuticals Inc. today announced it will present 18 research
posters on Latuda^® (lurasidone HCl), an atypical antipsychotic indicated for
the treatment of adult patients with schizophrenia, at the 166^th Annual
Meeting of the American Psychiatric Association (APA) in San Francisco. The
presentation includes results from analyses of two pivotal studies in patients
with depressive episodes associated with bipolar I disorder (bipolar
depression). These new data showed that LATUDA in the treatment of bipolar
depression, either as monotherapy or added to ongoing treatment with lithium
or valproate, was associated with low rates of change in weight, body mass
index (BMI), lipid parameters and measures of glycemic control.
The two pivotal studies evaluated the efficacy and safety of LATUDA as
monotherapy (PREVAIL 2) or adjunctive therapy (PREVAIL 1) for the treatment of
bipolar depression, and supported two supplemental New Drug Applications
(sNDAs) that were accepted by the U.S. Food and Drug Administration (FDA) on
October 30, 2012.
“Sunovion is pleased to present data from two extensive research programs that
studied LATUDA in patients with schizophrenia and bipolar depression,” said
Antony Loebel, M.D., Executive Vice President and Chief Medical Officer of
Sunovion Pharmaceuticals Inc. “We are proud of the contributions we are making
to improved understanding of these disorders where high unmet clinical needs
Effects of LATUDA on Metabolic Indices in Bipolar Depression
The LATUDA monotherapy (PREVAIL 2) and adjunctive therapy studies (PREVAIL 1)
were six-week, randomized, double-blind, placebo-controlled clinical trials
that evaluated the efficacy and safety of LATUDA as monotherapy (20-60 mg/day
or 80-120 mg/day vs. placebo, N=505) or adjunctive therapy (20-120 mg/day,
N=348) to lithium or valproate in patients with bipolar depression, with or
without rapid cycling (DSM-IV-TR). Changes from baseline to Week 6 in
metabolic parameters [lipids, glucose, weight, insulin and homeostatic model
assessment of insulin resistance (HOMA-IR)] were assessed [using rank ANCOVA
(LOCF) controlling for the baseline values of these metabolic parameters].
Results from the studies were as follows:
PREVAIL 2 (Monotherapy)
*Mean weight change from baseline for LATUDA vs. placebo was 0.64 vs. -0.09
lbs. (p=not significant).
*Weight gain from baseline (≥ 7%) occurred in 2.4% of patients treated with
LATUDA vs. 0.7% of patients treated with placebo.
*Mean changes from baseline in metabolic laboratory parameters were:
cholesterol -1.7 vs. -3.2 mg/dL, LDL -2.7 vs. -3.5 mg/dL, triglycerides
3.0 vs. 6.0 mg/dL, glucose 0.5 vs. 1.8 mg/dL, insulin 3.56 vs. 2.95 mU/L
and HOMA-IR 1.08 vs. 1.19, for LATUDA vs. placebo, respectively (p=not
significant for all comparisons).
PREVAIL 1 (Adjunctive Therapy)
*Mean weight change from baseline for LATUDA vs. placebo was 0.51 vs. 0.31
lbs. (p= not significant).
*Weight gain from baseline (≥ 7%) occurred in 3.1% of patients treated with
LATUDA vs. 0.7% of patients treated with placebo.
*Mean changes from baseline in metabolic laboratory parameters were:
cholesterol -3.0 vs. -3.8 mg/dL, LDL -3.2 vs. -2.0 mg/dL, triglycerides
9.0 vs. -6.2 mg/dL, glucose 0.9 vs. -0.3 mg/dL, insulin 1.66 vs. -0.16
mU/L and HOMA-IR 0.26 vs. -0.07, for LATUDA vs. placebo, respectively
(p=not significant for all comparisons).
Using the National Cholesterol Education Program (NCEP) adult treatment panel
criteria for metabolic syndrome, approximately 15% of patients met criteria
for metabolic syndrome (MetS) at study baseline, which is associated with risk
for diabetes and cardiovascular disease.
“Prior research has shown that patients with bipolar disorder are already at
high risk for metabolic syndrome,” said Loebel. “As such, it is critically
important that we continue to evaluate the effect of LATUDA on these key
measures of metabolic health, in both short and longer-term treatment.”
In PREVAIL 1, the most frequently reported adverse events were nausea,
somnolence, tremor, akathisia and insomnia. Discontinuation rates due to
adverse events were 6% for LATUDA and 7.9% for placebo. In PREVAIL 2, the most
frequently reported adverse events were nausea, headache, akathisia,
somnolence and sedation. Discontinuation rates due to adverse events were 6%
for LATUDA (either dose group) and 6% for placebo.
About Bipolar I Disorder and Bipolar Depression
Bipolar disorder, a mental illness characterized by debilitating mood swings,
affects approximately 10.4 million American adults.^1,2 Bipolar depression
refers to the depressive phase of bipolar disorder.^3 Symptoms of bipolar
depression include: extreme sadness, anxiety, fatigue, inactivity and
disinterest in usual activities, disruptions to sleeping patterns and
hopelessness.^1,4 When symptomatic, most people with bipolar disorder tend to
be depressed, rather than manic.^3 Bipolar disorder can also double a person’s
risk of early death from a range of medical conditions, including obesity,
diabetes and cardiovascular disease.^5,6,7 Bipolar disorder is the sixth
leading cause of disability worldwide^8and is among the top 10 leading causes
of disability in the United States (U.S.).^9
LATUDA is an atypical antipsychotic agent indicated for the treatment of
patients with schizophrenia. Efficacy was established in five six-week
controlled studies of adult patients with schizophrenia. The effectiveness of
LATUDA for longer-term use, that is, for more than six weeks, has not been
established in controlled studies. Therefore, the physician who elects to use
LATUDA for extended periods should periodically re-evaluate the long-term
usefulness of the drug for the individual patient.
The recommended starting dose for LATUDA for the treatment of patients with
schizophrenia is 40 mg once daily taken with food (at least 350 calories) with
no initial dose titration required. LATUDA has been shown to be effective in a
dose range of 40 mg/day to 160 mg/day. The maximum recommended dose is 160
mg/day. For patients with moderate and severe renal or hepatic impairment, the
recommended starting dose of LATUDA is 20 mg/day. The maximum recommended dose
is 80 mg/day in patients with moderate hepatic impairment and 40 mg/day in
patients with severe hepatic impairment. The recommended starting dose of
LATUDA in patients taking a moderate CYP3A4 inhibitor such as diltiazem is 20
mg/day with a maximum recommended dose of 80 mg/day. LATUDA should not be
administered with strong CYP3A4 inhibitors such as ketoconazole or strong
CYP3A4 inducers such as rifampin.
Please see Important Safety Information, including Boxed Warning below, and
full Prescribing Information at www.LATUDA.com.
LATUDA received FDA approval for the treatment of adult patients with
schizophrenia on October 28, 2010 and is available in the U.S. and Canada. On
October 30, 2012, the FDA accepted two supplemental New Drug Applications
(sNDAs) for the use of LATUDA as monotherapy and adjunctive therapy to lithium
or valproate, both to treat adult patients with depressive episodes associated
with bipolar I disorder (bipolar depression).
IMPORTANT SAFETY INFORMATION FOR LATUDA
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED
See full prescribing information for complete boxed warning.
*Elderly patients with dementia-related psychosis treated with
antipsychotic drugs are at an increased risk of death.
*LATUDA is not approved for the treatment of patients with dementia-related
LATUDA is contraindicated in the following:
*Any patient with a known hypersensitivity to lurasidone HCl or any
components in the formulation. Angioedema has been observed with
*Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole)
*Concomitant use with strong CYP3A4 inducers (e.g., rifampin).
WARNINGS AND PRECAUTIONS
Cerebrovascular Adverse Reactions, Including Stroke: In placebo-controlled
trials with risperidone, aripiprazole, and olanzapine in elderly subjects with
dementia, there was a higher incidence of cerebrovascular adverse reactions
(cerebrovascular accidents and transient ischemic attacks) including
fatalities compared to placebo-treated subjects. LATUDA 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 administration of antipsychotic drugs,
including LATUDA. NMS can cause hyperpyrexia, muscle rigidity, altered mental
status and evidence of autonomic instability (irregular pulse or blood
pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs
may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis),
and acute renal failure. The management of NMS should include: 1) immediate
discontinuation of antipsychotic drugs and other drugs not essential to
concurrent therapy; 2) intensive symptomatic treatment and medical monitoring;
and 3) treatment of any concomitant serious medical problems for which
specific treatments are available.
Tardive Dyskinesia (TD): TD is a syndrome consisting of potentially
irreversible, involuntary, dyskinetic movements that can develop in patients
with antipsychotic drugs. There is no known treatment for established cases of
TD, although the syndrome may remit, partially or completely, if antipsychotic
treatment is withdrawn. The risk of developing TD and the likelihood that it
will become irreversible are believed to increase as the duration of treatment
and the total cumulative dose of antipsychotic drugs administered to the
patient increase. However, the syndrome can develop, although much less
commonly, after relatively brief treatment periods at low doses. Given these
considerations, LATUDA should be prescribed in a manner that is most likely to
minimize the occurrence of TD. If signs and symptoms appear in a patient on
LATUDA, drug discontinuation should be considered.
Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases extreme and
associated with ketoacidosis or hyperosmolar coma or death, has been reported
in patients treated with atypical antipsychotics. Patients with risk factors
for diabetes mellitus (e.g., obesity, family history of diabetes) who are
starting treatment with atypical antipsychotics should undergo fasting blood
glucose testing at the beginning of and periodically during treatment. Any
patient treated with atypical antipsychotics should be monitored for symptoms
of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness.
Patients who develop symptoms of hyperglycemia during treatment with atypical
antipsychotics should undergo fasting blood glucose testing. In some cases,
hyperglycemia has resolved when the atypical antipsychotic was discontinued;
however, some patients required continuation of anti-diabetic treatment
despite discontinuation of the suspect drug.
Dyslipidemia: Undesirable alterations in lipids have been observed in
patients treated with atypical antipsychotics.
Weight Gain: Weight gain has been observed with atypical antipsychotic use.
Clinical monitoring of weight is recommended.
Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors,
LATUDA elevates prolactin levels. Galactorrhea, amenorrhea, gynecomastia, and
impotence have been reported in patients receiving prolactin-elevating
compounds. In short-term, placebo-controlled studies, the median change from
baseline to endpoint in prolactin levels for LATUDA-treated females was -0.2
ng/mL and was 0.5 ng/mL for males. The proportion of female patients with
prolactin elevations ≥5x ULN was 5.7% for LATUDA-treated patients versus 2.0%
for placebo-treated female patients. The proportion of male patients with
prolactin elevations > 5x ULN was 1.6% versus 0.6% for placebo-treated male
Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia has been
reported during treatment with antipsychotic agents. Agranulocytosis
(including fatal cases) has been reported with other agents in the class.
Patients with a preexisting low white blood cell count (WBC) or a history of
drug induced leukopenia/neutropenia should have their complete blood count
(CBC) monitored frequently during the first few months of therapy, and LATUDA
should be discontinued at the first sign of a decline in WBC in the absence of
other causative factors.
Orthostatic Hypotension and Syncope: LATUDA may cause orthostatic hypotension.
Orthostatic vital signs should be monitored in patients who are vulnerable to
hypotension and in patients with known cardiovascular disease or
Seizures: LATUDA should be used cautiously in patients with a history of
seizures or with conditions that lower seizure threshold (e.g., Alzheimer’s
Potential for Cognitive and Motor Impairment: In short-term,
placebo-controlled trials, somnolence was reported in 17.0% (256/1508) of
patients treated with LATUDA compared to 7.1% (50/708) of placebo patients,
respectively. Patients should be cautioned about operating hazardous
machinery, including motor vehicles, until they are reasonably certain that
therapy with LATUDA does not affect them adversely.
Body Temperature Regulation: Disruption of the body’s ability to reduce core
body temperature has been attributed to antipsychotic agents. Appropriate care
is advised when prescribing LATUDA for patients who will be experiencing
conditions that may contribute to an elevation in core body temperature, e.g.,
exercising strenuously, exposure to extreme heat, receiving concomitant
medication with anticholinergic activity, or being subject to dehydration.
Suicide: The possibility of suicide attempt is inherent in psychotic illness
and close supervision of high-risk patients should accompany drug therapy.
Prescriptions for LATUDA should be written for the smallest quantity of
tablets consistent with good patient management in order to reduce the risk of
Dysphagia: Esophageal dysmotility and aspiration have been associated with
antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity
and mortality in elderly patients, in particular those with advanced
Alzheimer’s dementia. LATUDA and other antipsychotic drugs should be used
cautiously in patients at risk for aspiration pneumonia.
Commonly Observed Adverse Reactions: (incidence ≥ 5% and at least twice the
rate of placebo) in patients treated with LATUDA were somnolence, akathisia,
nausea and parkinsonism.
Before prescribing LATUDA, please read the full Prescribing Information,
including Boxed Warning at www.LATUDA.com.
About Sunovion Pharmaceuticals Inc. (Sunovion) is a leading pharmaceutical
company dedicated to discovering, developing and commercializing therapeutic
products that advance the science of medicine in the Psychiatry & Neurology
and Respiratory disease areas and improve the lives of patients and their
families. Sunovion's drug development program, together with its corporate
development and licensing efforts, has yielded a portfolio of pharmaceutical
products including LATUDA^® (lurasidone HCl) tablets, LUNESTA^® (eszopiclone)
tablets, XOPENEX^® (levalbuterol HCI) inhalation solution, XOPENEX HFA^®
(levalbuterol tartrate) inhalation aerosol, BROVANA^® (arformoterol tartrate)
inhalation solution, OMNARIS^® (ciclesonide) nasal spray, ZETONNA^®
(ciclesonide) nasal aerosol and ALVESCO^® (ciclesonide) inhalation aerosol.
Sunovion, an indirect, wholly-owned subsidiary of Dainippon Sumitomo Pharma
Co., Ltd., is headquartered in Marlborough, Mass. More information about
Sunovion Pharmaceuticals Inc. is available at www.sunovion.com.
About Dainippon Sumitomo Pharma Co., Ltd. (DSP)
Dainippon Sumitomo Pharma Co., Ltd. (DSP) is a multi-billion dollar, top-ten
listed pharmaceutical company in Japan with a diverse portfolio of
pharmaceutical, animal health and food and specialty products. DSP aims to
produce innovative pharmaceutical products in the Psychiatry & Neurology
field, which has been designated as one of the two key therapeutic areas. DSP
is based on the merger in 2005 between Dainippon Pharmaceutical Co., Ltd., and
Sumitomo Pharmaceuticals Co., Ltd. Today, DSP has more than 7,000 employees
worldwide. Additional information about DSP is available through its corporate
website at www.ds-pharma.com.
LATUDA ^ is a registered trademark of Dainippon Sumitomo Pharma Co., Ltd.
LUNESTA, XOPENEX, XOPENEX HFA and BROVANA are registered trademarks of
Sunovion Pharmaceuticals Inc. OMNARIS and ALVESCO are registered trademarks of
Nycomed GmbH, used with permission.
Sunovion Pharmaceuticals Inc. is a U.S. subsidiary of Dainippon Sumitomo
Pharma Co., Ltd.
^© 2013 Sunovion Pharmaceuticals Inc.
For a copy of this release, visit Sunovion Pharmaceutical Inc.’s web site at
^1 National Institute of Mental Health. Bipolar Disorder. [Internet] Available
Accessed July 26, 2012.
^2 Bipolar Disorder.” Decision Resources. Table 2-1: Number of Total Prevalent
Cases of Bipolar Disorder in the Major Pharmaceutical Markets, by Subtype,
2008-2018. Waltham, MA. December 2009.
^3 The Depression and Bipolar Support Alliance. Mood Disorders and Different
Kinds of Depression. [Internet]. Available from:
Accessed March 7, 2012.
^4 The Journal of the American Medical Association. Bipolar Disorder Patient
Page. [Internet]. Available from:
http://jama.ama-assn.org/cgi/reprint/301/5/564.pdf. Accessed June 22, 2012.
^5 Roshanaei-Moghaddam, B, Katon, W. Premature Mortality from General Medical
Illnesses among Persons with Bipolar Disorder: A Review. Psychiatric Services.
^6 Fagiolini A et al. Bipolar Disorder and the Metabolic Syndrome: Causal
Factors, Psychiatric Outcomes and Economic Burden. CNS Drugs. 2008;
^7 Mcintyre R. et al. Bipolar Disorder and Diabetes Mellitus: Epidemiology,
Etiology, and Treatment Implications. Annals of Clinical Psychiatry. 2005;
^8 National Alliance on Mental Illness. The Impact and Cost of Mental Illness:
The Case of Bipolar Disorder. [Internet]. Available from: http://www.nami.org.
Accessed March 29, 2013 (To Access: Communities, Living With, Bipolar
^9 National Alliance on Mental Illness. A Primer on Depressive, Bipolar and
Anxiety Illnesses: Facts for Policymakers. [Internet]. Available from:
http://www.nami.org. Accessed March 29, 2013 (To Access: Inform Yourself,
About Public Policy, Policy Research Institute, Policymakers Toolkit).
Sunovion Pharmaceuticals Inc.
Patricia Moriarty, 508-787-4279
Senior Director, Corporate Communications
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