MARLBOROUGH, Mass.--(BUSINESS WIRE)--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 166th 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 remain.”
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 worldwide8 and is among the top 10 leading causes of disability in the United States (U.S.).9
About LATUDA
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 PSYCHOSIS
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 psychosis.
CONTRAINDICATIONS
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 lurasidone.
- 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.
Metabolic Changes
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 patients.
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 cerebrovascular disease.
Seizures: LATUDA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold (e.g., Alzheimer’s dementia).
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 overdose.
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.
ADVERSE REACTIONS
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
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 www.sunovion.com
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