|[May 09, 2012]
New Study Shows Patients Can Effectively be Switched to Latuda® (lurasidone HCl) from Other Antipsychotic Agents
MARLBOROUGH, Mass. --(Business Wire)--
Sunovion Pharmaceuticals Inc. today announced results from an open-label
study that switched clinically stable, but symptomatic adult outpatients
with schizophrenia from other antipsychotic agents to LATUDA (lurasidone
HCl) . These data were presented at the 165th
Annual Meeting of the American Psychiatric Association in Philadelphia,
This 6-week open-label study included 244 patients who were clinically
stable for at least eight weeks prior to the start of the study and had
been on stable doses of other antipsychotic agents for at least four
weeks. The study's primary endpoint was time to treatment failure
(defined as discontinuation due to insufficient clinical response or an
adverse event, including exacerbation of underlying disease). In
addition, the study was intended to assess the safety and tolerability
of switching patients from other antipsychotic agents to LATUDA.
Eligible patients were randomized to one of three LATUDA dosing regimens
for the initial two weeks of the study: 1) 40 mg/day for two weeks; 2)
40 mg/day for one week, then an increase to 80 mg/day on Day 8 for Week
2 (uptitration group); and 3) 80 mg/day for two weeks. LATUDA was then
flexibly dosed (40-120 mg/day) for the subsequent four weeks of the
study across each of the three dosing regimens. The pre-switch
antipsychotic agent was tapered by Day 7 to 50% of the original dose and
discontinued by the end of Week 2.
The proportion of patients across all LATUDA doses (19/240, 7.9%) that
met pre-specified criteria for treatment failure (based on initial
randomized dose groups) was as follows:
LATUDA 40 mg/day: 6.9% (5/72)
LATUDA 40/80 mg/day (uptitration group): 9.2% (8/87)
LATUDA 80 mg/day: 7.4% (6/81)
The overall discontinuation rate was 18.9%, with 1.2% of patients
discontinuing treatment due to insufficient clinical response and 6.6%
due to adverse events.
For patients who were taking concomitant antidepressants, mood
stabilizers or antipsychotics at study initiation, approximately half
(49.5%) of these patients discontinued use of the concomitant agent by
Adverse events (at least 5% in all LATUDA doses) observed in this study
included nausea, insomnia, akathisia, headache, vomiting, somnolence and
dry mouth. Results for all LATUDA-treated patients were as follows:
Change from baseline at Week 6 LOCF endpoint:
Weight*: -0.7 lbs (n=220)
Cholesterol†: -1.0 mg/dL (n=219)
Triglycerides†: -6.0 mg/dL (n=219)
Glucose†: -1.0 mg/dL (n=219)
Prolactin†: +0.5 (n=219)
Additional data showed that LATUDA-treated patients experienced
improvements as assessed by the Positive and Negative Syndrome Scale
total (PANSS, -5.8), Clinical Global Impression-Severity scale (CGI (News - Alert)-S,
-0.3) and the Calgary Depression Scale for Schizophrenia (CDSS, -1.3).
These results were based on changes from baseline for LATUDA-treated
patients; there was no placebo or other comparator. Results were similar
for all three switch strategies.
"An important measure of the acceptability of any antipsychotic agent
is how many people are taking it six weeks later," said Joseph McEvoy,
M.D., Professor of Psychiatry and Behavioral Sciences at Duke University
Medical Center. "The completion rate was notable in this study of
LATUDA, with more than 80% of patients making it to six weeks. And
when patients did discontinue, only 1% did so due to insufficient
"Schizophrenia is a complex disorder whose treatment often requires
switching antipsychotic agents," said Antony Loebel, M.D., Executive
Vice President and Chief Medical Officer of Sunovion Pharmaceuticals
Inc. "We designed this study to help physicians understand how they
could switch patients to LATUDA in a real-world setting."
Overall, these findings indicate that switching to LATUDA initiated at
therapeutic doses of 40 or 80 mg/day, or uptitrated from 40 mg/day to 80
mg/day, was comparably well-tolerated and effective. In addition, taper
and discontinuation of the pre-switch antipsychotic agent over a
two-week period was safe and well-tolerated. Since the results of
switching to LATUDA were similar for the three initial dose groups, the
choice of specific switch strategy may be based on individual need and
LATUDA received U.S. Food and Drug Administration (FDA) approval for the
treatment of schizophrenia on October 28, 2010 and is available in
pharmacies across the U.S. and Puerto Rico.
LATUDA is an atypical antipsychotic indicated for the treatment of
patients with schizophrenia. Efficacy was established in five 6-week
controlled studies of adult patients with schizophrenia. The
effectiveness of LATUDA for longer-term use, that is, for more than 6
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
The recommended starting dose for LATUDA 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 s rifampin.
Please see Important Safety Information, including Boxed Warning below,
and full Prescribing Information at www.LATUDA.com.
IMPORTANT SAFETY INFORMATION FOR LATUDA
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH
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
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
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
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.
Schizophrenia is a chronic, disabling and serious brain disorder that
affects approximately 2.4 million American adults or 1 in 100 people.
Schizophrenia is characterized by symptoms such as hallucinations,
delusions, disorganized thinking, lack of emotion, lack of energy, as
well as problems with memory, attention and the ability to plan,
organize and make decisions.
About Sunovion Pharmaceuticals Inc. (Sunovion)
Sunovion is a leading pharmaceutical company dedicated to discovering,
developing and commercializing therapeutic products that advance the
science of medicine in the central nervous system (CNS) 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® brand lurasidone
HCl, LUNESTA® brand eszopiclone, XOPENEX® brand
levalbuterol HCl Inhalation Solution, XOPENEX HFA® brand
levalbuterol tartrate inhalation aerosol, BROVANA® brand
arformoterol tartrate inhalation solution, OMNARIS® brand
ciclesonide nasal spray and ALVESCO® brand ciclesonide HFA
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)
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 CNS field, which has been designated as the key
therapeutic area and will also focus in on other specialty disease
categories with significant unmet medical needs, which are designated as
frontier 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.
Sunovion Pharmaceuticals Inc. is a U.S. subsidiary of Dainippon Sumitomo
Pharma Co., Ltd. © 2012 Sunovion Pharmaceuticals Inc.
For a copy of this release, visit Sunovion's web site at www.sunovion.com
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