`
` Loiudd
`(lurasidone HCI) tablets
`20mg I 40mg I 60mg I 80mg I 120mg
`
`Please see important Safety Information, including Boxed Warnings,
`on pages 66-67 and enclosed full Prescribing Information.
`
`Look inside to learn more about an
`
`FDA-approved atypical antipsychotic
`
`Product Monograph
`
`INDICATIONS
`
`LATUDA is indicated for treatment of adult and adolescent patients age 13 to 17 years with schizophrenia and in adult
`patients with major depressive episodes associated with bipolar l disorder (bipolar depression) as monotherapy and
`as adjunctive therapy with lithium or valproate.
`
`IMPORTANT SAFETY INFORMATION FOR LATUDA
`
`INCREASED MORTALITY iN ELDERLY PATiENTS WITH DEMENTIA—RELATED PSYCHOSIS;
`and SUiCIDAI. THOUGHTS AND BEHAViORS
`
`Increased Mortality In Elderly Patients with Dementia-Related Psychosis
`Elderly patients with dementia-related psychosis treated with antipsychotlc drugs are at an
`increased risk of death. LATUDA is not approved for the treatment of patients with dementia-
`related psychosis.
`
`Suicidal Thoughts and Behaviors
`Antidepressants increased the risk of suicidal thoughts and behaviors in patients aged 24 years
`and younger. Monitor for clinical worsening and emergence of suicidal thoughts and behavior.
`LATUDA is not approved for use in pediatric patients with depression.
`
`Please see additional Important Safety Information. including Boxed Warnings.
`on pages 66-67 and enclosed full Prescribing information.
`
`CONFIDENTIAL
`
`1
`
`Exhbit2070
`Slayback v. Sumitomo
`“2202001053
`
`

`

`iMPOR’TANT SAFETY lNFGRMA‘fiGN F‘OR LA?UDA
`
`Contraindications: LATUDA is contraindicated in the following:
`
`° Known hypersensitivity to ILIrasidone HCI or any components in the formulation.
`Angioedema has been observed with lurasidcne
`
`‘ Strong CYP3A4 inhibitors (9.9., ketoconazole)
`
`° Strong CYP3A4 inducers (9.9)., rifampin)
`
`For more information please visit us at: www.LATUDAhcp.com
`
`Please see additional Important Safety information. including Boxed Warnings.
`on pages 66-67 and enclosed full Prescribing Information.
`
`CONFIDENTIAL
`
`LATUDA04006171
`
`2
`
`

`

`BIPOLAR DISORDER OVERVIEW ........................................................ 4
`
`Summary of Bipolar I Disorder ....................................................... 8
`
`Bipolar Disorder Clinical and Economic Burden ......................................... 6
`
`SCHIZOPHRENIA OVERVIEW ........................................................... 10
`
`Schizophrenia Clinical and Economic Burden ........................................... 11
`
`Summary of Schizophrenia .......................................................... 15
`
`LATUDA PRODUCT PROFFLE ............................. . ............................. 16
`
`indications ......................................................................... 16
`
`Dosage and Administration .......................................................... 17
`
`Clinical Pharmacology ............................................................... 18
`
`LATUDA Efficacy .................................................................. 20
`
`Major Depressive Episodes Associated With Bipolar I Disorder (Bipolar Depression) ..... 20
`
`Schizophrenia .................................................................. 28
`
`LATUDA Safety 8. Tolerability ........................................................ 4O
`
`LATUDA Safety Database: Adults With Bipolar Depression and Schizophrenia ........... 40
`
`Major Depressive Episodes Associated With Bipolar l Disorder {Bipolar Depression) ...... 41
`
`Schizophrenia .................................................................. 50
`
`Summary of the Efficacyr and Tolerability of LATUDA ................................... 65
`
`IMPORTANT SAFETY INFORMATION AND JNOFCATIONS FOR LATUDA ...................... 66
`
`REFERENCES ....................................................................... 68
`
`CONTACT INFORMATION ............................................................. 70
`
`FULL PRESCRIBING ENFORMATIDN .............................................. Enclosed
`
`
`
`CONFIDENTIAL
`
`LATU DA04006172
`
`
`
`
`magma Elf!) tablets
`WIWIEWWHW 3
`
`3
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`

`

`
`
`BSWLAR NSfiWER fiVEWiEW
`
`Bipolar disorder is a mentai illness characterized by debilitating mood swings.l The lifetime
`prevalence estimate for bipolar disorder has been estimated to be approximately 4% to 5% of
`Americans over the age of 18.2 Therefore, it is estimated that as many as i2.3 million people in the
`United States are affected by bipolar disorder.2 Bipolar disorder is among the top 10 leading causes
`of disability in the United States.3
`
`Bipolar disorder shows different patterns of illness and is suggested to be a spectrum of disorders.
`However. the main categories of bipolar disorder are bipolar | disorder and bipolar ll disorder. The
`fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM‘S) criteria for a
`diagnosis of bipolar l disorder includes a history of i or more major depressive episodes and at least
`1 episode of mania. DSM-S criteria for bipolar Ii disorder inciudes a history of i or more major
`depressive episodes and hypornanic episodes. without true manic episodes.4
`
`Mania is defined as a distinct period of abnormally and persistently eievated. expansive. or irritable
`mood and abnormally and persistently increased goal-directed activity or energy, lasting at least 1
`week and present most of the day. nearly every day (or any duration if hospitalization is necessary).
`should be present.“4 During this period of mood disturbance and increased energy or activity. 23 of
`the following symptoms (4 if the mood is only irritable) need to be present to a significant degree
`and noticeable“:
`
`1. inflated seif—esteem or grandiosity
`
`2. Decreased need for sleep (eg. feels rested after only 3 hours of sleep)
`
`3. More talkative than usual or pressured to keep talking
`
`4. Flight of ideas or subjective experience that thoughts are racing
`
`5. Distractibiiity
`
`6. lncrease in goal—directed activity or psychomotor agitation
`7. Excessive involvement in activities that have a high potential for painfui consequences
`
`in general. the mood disturbance is sufficiently severe to cause marked impairment in social or
`occupational functioning or to necessitate hospitalization to prevent harm to self or others. or
`psychotic features are present.‘1 The episode should not be attributable to the physiologic effects of
`a substance of abuse. medication. or other medicai condition.
`
`Hypomania is defined as a distinct period of abnormaily and persistently elevated, expansive.
`or irritabie mood and abnormally and persistently increased activity or energy. lasting at least
`4 consecutive days and present most of the day. nearly every day“
`
`A major depressive episode is defined by the presence 0125 of the following symptoms during the
`same 2*week period, and represents a change from previous functioning. At least one of the
`symptoms is either (i) depressed mood or (2) loss of interest or pleasure.
`
`i. Depressed mood most of the day. nearly every day. as indicated by either subjective report or
`observation made by others
`
`2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly
`every day
`
`3. Significant weight ioss when not dieting or weight gain
`
`4. Insomnia or hypersomnia neariy every day
`
`5. Psychomotor agitation or retardation nearly every day
`
`6. Fatigue or loss of energy nearly every day
`
`7. Feelings of worthlessness or excessive or inappropriate guilt nearly every day
`
`8. Diminished ability to think or concentrate. or indecisiveness. nearly every day
`
`9. Recurrent thoughts of death (not just fear of dying). recurrent suicidal ideation without a
`specific plan. or a suicide attempt or a specific plan for committing suicide
`
`Symptoms of a major depressive episode cause clinically significant distress or impairment in social.
`occupational, or other important areas of functioning!1 The episode should not be attributable to
`the physiologic effects of a substance of abuse. medication. or other medical condition.
`
`4
`
`CONFIDENTIAL
`
`LATUDA04006173
`
`4
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`

`

`Ari example of a bipoiar l disorder cycle is shown in Figure 1. Diagnosis of bipolar i disorder is differentiated from
`bipoiar ii disorder by determining whether there have been any past episodes of mania.
`
`Upper iimit oi "norms?" mood
`(happiness, fair}
`
`{sodoe ss. grief}
`
`"Good times“
`mmwwwwmww
`
`§ssi
`
`"Bad times"
`
`Lower iimit of "normai” mood
`
`Men and women are equally iikely to deveiop bipoiar disorder over their lifetime and the disease tends to have an
`onset in early adulthood.5 Figure 2 shows the proportion of time spent ill during clinical visits for bipolar | disorder
`(N = 572) from one study. As for differences between genders. this study showed that women had a significantly
`greater number of prior depressive episodes and hospitalizations for depression.5 Although there was no difference
`in time spent in mania between the 2 groups in this study, there was a trend showing that men had a greater number
`of iifetime hospitalizations for mania?
`
`gi ‘ Severe depression
`
`Severe fill llil
`
`a Illilil mania
`fl Euihymia
`a Hill! depression
`
`g:
`a a Moderate depression
`
`Women (35.4%) vs men (29.3%) for depressed visits; women {49.3%} vs men (56.1%) for euthymic visits;
`women (15.1%) vs men (14.6%) for hypomanic or manic visits.
`
`A common misconception about the disease course of bipoiar disorder is that patients spend an equal amount of
`timer when ill. either manic or depressed. Contrary to this belief, a longitudinal study {approximately 13 years of
`follow-up) of patients with bipolar I disorder demonstrated that depressive symptoms (32% of totai follow-up weeks)
`seem to predominate over manic/hypomanic symptoms {9% of Weeks) or cyclingr‘mixed symptoms (6% of weeks).5
`This is termed bipoiar depression and refers to the depressive phase of bipolar disorder. Symptoms of bipolar
`depression inciude: extreme sadness, anxiety, fatigue. hopelessness, inactivity and disinterest in usuai activities,
`disruptions to sleeping and eating patterns. and thoughts of death or suicide.‘ This sometimes prevents eariy
`diagnosis of bipoiar disorder since. when symptomatic, most peopie with bipoiar I disorder tend to spend about 70%
`of the time in the depressed state.6
`
`Furthermore, monitoring for symptoms consistent with bipolar disorder is important since approximateiy 15% of
`people diagnosed with unipoiar depression, and who self'report episodes consistent with mania, may be at risk for
`undiagnosed bipolar disorder?
`
`CONFIDENTIAL
`
`LATUDA04006174
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`5
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`

`

`Bipolar disorder Clinical and Economic Burden
`
`fiisease harden
`
`Bipolar disorder is a burdensome illness characterized by recurrent episodes of major depressive
`episodes and mania (or mixed episodes of the 2} or hypomanla. In a longitudinal study
`(approximately 13 years of follow-up) of patients with bipolar | disorder (N : 146), patients were
`symptomatically ill nearly half of all of the weeks they were followed? Additionally. patients with
`bipoiar I disorder changed symptom status an average of 5 times per year and polarity more than
`3 times per year.‘S These events take a heavy toll on a patient‘s health status and affect family.
`social. and work relationships.
`
`Mortality Risk From General medical Conditions and Life Expectancy
`
`Bipolar disorder can also double a person’s risk of early death from a range of medical conditions.a
`Patients with bipolar disorder have increased risk for metabolic syndrome. high blood glucose and
`cholesterol. high blood pressure. and obesity.9 These factors are closely associated with the risk for
`cardiovascular disease (CVD).
`
`Mortality ratios for death from general medical conditions, such as cardiovascular. respiratory.
`cerebrovascular. and endocrine disorders. are significantly higher among patients with bipolar
`disorder compared with persons with no psychiatric illness.9 Recently. in a large population-based
`study of l7.lOl patients with bipolar disorder it was shown that mortality from CVD was 2-fold higher
`in this population compared with the generai population. and 38% of all deaths in persons with
`bipolar disorder were caused by CVD.9 Furthermore, patients with bipolar disorder died of CVD
`approximately l0 years earlier than the general population and 5—year survival rates (by patient age}
`after first hospital admission for CVD were significantly lower among patients with bipolar disorder
`than individuals in the general population {Figure 3).9
`
`.
`I
`F,.....9...n.............n-u.nauu«.~n-7-ann.gun-nwonn Iv-
`
`on:
`
`an»
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`--
`
`~ nu Population
`
`a?
`E3‘[—=
`m
`
`m Bipolar
`
`2
`
`3
`
`Time Since Diagnosis. y
`
`Biological factors, unhealthy lifestyle (eg. smoking and unhealthy diet). ad verse medication effects.
`and disparities in healthcare are all possible underlying contributors to increased mortality in
`hipoiar disorder.8 It has been shown that life expectancy in patients with bipolar disorder is reduced
`by nearly i4 years in men and by l2 years in women.“1
`
`LATUDA has not been shown or indicated to impact mortality
`in prospective. randomized. placebo-controlled trials.
`
`LATU DA04006175
`
` 6
`
`a3.}
`gs:35
`e33!
`§
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`CONFIDENTIAL
`
`6
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`

`

`Economic Banter:
`
`Estimates of healthcare utilization costs for patients with bipolar disorder are 2.5 times greater than for general
`medical outpatients.‘1 in 2002. a US population-based survey of people with bipoiar depression showed higher
`healthcare utilization patterns over 12 months compared with people who had unipolar depression.La More frequent
`office visits, emergency care visits, hospitalizations. and use of social services were reported by patients with
`bipolar depression compared with patients with unipolar depression (Figure 4}_12 For example. patients with bipolar
`depression were twice as likely to seek counseling and 3.5 times as likely to need a psychiatric hospital stay than
`patients with unipolar depression.
`
`
`
`E Bipolar depression
`
`fl Unipolar depression
`
`”.3 Control subjects
`
`
`
`40
`
`30
`
`2|!
`
`
`
`
`
`
`PercentofPatientsReporting
`
`.
`
`v.2
`
`I
`
`u
`
`
` . .
`Emergency Rinornf
`t’sychlatrlc
`Urgent Care Visit
`Hospital Stay
`
`
`
`
`
`Minary
`Care Visit
`
`Psychiatrist
`Visit
`
`Psychutoglstf
`Counselor Visit
`
`Substance abuse!
`Social Services
`
`LATUDA has not been shown or indicated to impact healthcare costs in prospective, randomized. placebo-controlled trials.
`
`Resident Symptoms and dedication donadherence Are Factors Associated with the Captioned
`Burden of Bipoiar Depression
`
`In the large Systematic Treatment Enhancement Program for Bipolar Disorder (STEP—BB) study. patients with bipolar
`disorder were followed for up to 2 years.13 two observations were made about patients who had yet to recover from
`their symptoms in this study. The first was that. despite appropriate clinical treatment based on availabie guidelines.
`nearly 50% of the participants experienced a recurrence of their symptoms by the end of the 2-year followup
`period.13 The second observation was that 70% of recurrence episodes were to a depressed state and the risk for
`recurrent depressive episodes increased by 14% for every depressive symptom present at recovery.‘3 This study
`confirmed that residual symptoms eariy in recovery predict recurrence, particularly for the depression associated
`with bipolar disorder.13 In one other study. patients recovering with residual symptoms experienced a subsequent
`major episode approximateiy 3 times faster than patients recovering without residual symptoms.I4
`
`Treatment nonadherence in bipolar disorder is a common occurrence. A study evaluated adherence to antipsychotic
`therapy with aripiprazole. quetiapine. and ziprasidone in the 6 months foliowing hospitalization of 84 patients with
`bipolar disorder.:5 in the 6 months following hospitalization, patients with bipolar disorder received medication
`enough to cover only 37% of their follow-up days.‘5 Several reasons for poor adherence were discussed including
`symptoms of the disease itself. medication side effects. substance abuse. tack of support systems. stress. and
`inadequate patient~heaithcare provider relationships.‘5 Ciinical features that have been shown to be significantly
`associated with poor adherence included rapid bipolar cycling. suicide attempts. earlier onset of iliness. and current
`anxiety or alcohol use disorder (P<O.05).16
`
`These data suggest that there is a need to appropriately treat the depressive episodes associated with bipolar
`disorder and to provide education to patients and their caregivers on the importance of medication adherence
`to maintain disease stability.
`
`LATUDA has not been shown or indicated to impact adherence
`in prospective, randomized, piacebo-controlied triais
`
`CONFIDENTIAL
`
`T
`
`LATUDA04006176
`
`7
`
`

`

`Summary of Bipolar l Disorder
`
`Bipolar l disorder is a chronic mood disorder associated with high rates of disability and medical
`comorbidities. premature mortality from general medical conditionsr in particular CVD, and risk of
`suicide. Aithough manic episodes are a key diagnostic factor of bipolar l disorder, patients will spend
`a high proportion of their symptomatic days in a depressed state and these symptoms tend to recur
`if inadeq uateiyr treated.
`
`Furthermore, since definitive diagnosis is sometimes delayed, information from previous medical
`records as well as family, friends, and coworkers may aid in the more timeiy diagnosis of bipoiar
`disorder. in turn. bipolar disorder is an important consideration in the differential diagnosis of
`major depressive disorder.
`
`LATUDA has not been shown or indicated to impact mortality
`in prospective, randomized, placebo-controlled trials.
`
` 8
`
`CONFIDENTIAL
`
`LATU DA04006177
`
`8
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`

`

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`3893833483?
`
`CONFIDENTIAL
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`9
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`LATUDA04006178
`
`9
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`

`

`mmnmwmmufigfiéfifii‘i‘
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`sneeeeiamteadszmeaeeaa_
`
`
`
`10
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`CONFIDENTIAL
`
`SCHEZQPHRENEA QVERVHEW
`
`Addhs
`
`Schizophrenia is a widespread mental iliness affecting more than 2 million Americans.“18 it affects
`both men and women. with symptoms typically beginning in adoiescence and early aduithood.“3
`
`The etiology of schizophrenia is multifactorial and poorly understood.” Although a direct biologicai
`cause has not been determined, genetic and environmental factors appear to piay a rote?" Evidence
`suggests that patients with schizophrenia have multiple abnormalities in brain anatomy.20
`
`Schizophrenia has 4 recognized clinical stages based on a patient's overall level of functioning:
`premorbid, prodromal. progressive. and resid ual.3°-2‘ The mean age range of these stages and the
`associated decline in functioning are presented in Figure 5.
`
`m
`.5
`c:
`uu
`.9.
`5n.
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`g
`see
`
`.<xéflfil
`
`fi Premorbid
`fi Prodromai
`39::
`as i’rogressive
`Residual
`
`Age (fears)
`
`‘isgaiffieegég
`WNW
`40
`
`Adapted from Lewis 0A. Lieberman JR. Neuron. 2000:38t2}1325‘334.
`
`The characteristic symptoms of schizophrenia involve a range of cognitive, behavioral, and
`emotional dysfunctions, but no singie symptom is pathognomonic of the disorder. The diagnosis
`involves the recognition of a constellation of signs and symptoms associated with impaired
`occupationai or social functioning. individuals with the disorder will vary substantiaily on most
`features. as schizophrenia is a heterogeneous clinicai synd rorne.‘8 DSM-S diagnostic criteria for
`schizophrenia require that two or more of the loliowing are each present for a significant portion
`of time during a 1-month period (or iess if successfuily treated). At ieast one of these must be (1},
`(2). or (3)13:
`
`3. Delusions
`2. Haliucinations
`
`3. Disorganlzed speech (eg, frequent deraiiment or incoherence)
`
`4. Grossly disorganized or catatonic behavior
`5. Negative symptoms (lo. diminished emotional expression or avolition)
`
`Furthermore. for a significant portion of the time since the onset of the disturbance. level of
`functioning in one or more major areas. such as work, interpersonal relations, or self-care, is
`markedly below the level achieved prior to the onset (or when the onset is in childhood or
`adolescence. there is failure to achieve expected level of interpersonal. academic. or occupationai
`functioning).‘3 Continuous signs of the disturbance persist for at least 6 months. This 6-month
`
`1 0
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`LATU DA04006179
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`10
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`

`period must inciude at least one month of symptoms (or less if SUccessfuily treated) that meet the criteria Eisted
`above (ie. active-phase symptoms) and may include periods of prodromal or residual symptoms. During these
`prodromal or residual periods. the signs of the disturbance may be manifested by only negative symptoms or by two
`or more symptoms listed above if they present in an attenuated form (eg, odd beliefs. unusual perceptuai
`experiences).'8 Other symptoms of schizophrenia may inciude hostiiity. excitement. emotional and sociai withd rawai.
`uncooperativeness, as well as impaired attention, executive functioning. and verbal fluency.22 Schizoaffective
`disorder and depressive or bipoiar disorder with psychotic features should be ruled out. as well as disturbances
`attributable to a drug of abuse or medication. or another Inedicai condition.'3 if there is a history of autism or
`communication disorder in chiidhood, then a diagnosis of schizophrenia is made only if prominent deiusions or
`hallucinations. in addition to other required symptoms of schizophrenia. are also present for at least one month.‘8
`
`Adolescents
`
`Approximately one-third of individuals develop schizophrenia before the age of 18.23 Adolescents age 13 to i? years
`with schizophrenia are diagnosed according to the same criteria as adults. though it is important to note that the
`disorder presents differently in these younger individuals. making its recognition more difficult. Adolescent-onset
`schizophrenia is characterized by a more insidious onset with a relative lack of symptom specificity in the early
`stages of the disease. the potentiai for more prominent negative symptoms. frequentiy disorganized behavior or
`dysfunctional ways of thinking. and iess complex deiusions and hallucinations. The duration of untreated psychosis
`can be 3.5 times longer in patients with early-onset schizophrenia versus those with adult-onset schizophrenia?“
`
`Short-term outcomes appear worse for adolescents with schizophrenia than for their adult counterparts. Over time.
`patients can typicaily expect a chronic. unremitting course with severe impairment as aduits. However, this path can
`vary considerably in terms of impairment level and sociai and psychiatric support needed?5
`
`Additional clinicai resources are needed to assist healthcare professionais with identifying schizophrenia in
`adolescents. The stigma associated with the illness can deiay communication of an actuai diagnosis to the patient
`and famiiyfimfi The severe and extended clinicai course and poor outcomes associated with adolescent
`schizophrenia highlight the need for early recognition. diagnosis. and intervention.“-25
`
`Schtzepi‘ireaia Ciiaisai and Retreats Burden
`
`Bisease harder: and Life Expectancy
`
`Although schizophrenia is a brain disorder. it has been shown to adverseiy affect not only mentai. but also overali
`physical health. ieading to increased morbidity and mortalityflofl
`
`The life expectancy of people with mental illness is. on average. 13 to 30 years shorter than that of the general
`population? The cause of premature mortality is largely attributed to coronary heart disease (Figure 63.28
`
`
`
`Life Expectancy {years}
`
`30
`
`40
`
`schizop enla
`i
`flflithnutsrhiznnhrenia
`
`50
`
`LATUDA has not been shown or indicated to impact mortality or life expectancy
`in prospective, randomized. piacebo-controiied triais.
`
`CONFIDENTIAL
`
`11
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`LATUDA04006180
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`

`Cardiavascstar Risk
`
`Coronary heart disease accounts for one-half to threevfourths of deaths in patients with
`schizophrenia as compared with about one-third of deaths in the generai populations?8 Rates of
`cardiovascuiar risk factors. including obesity, cigarette smoking. diabetes. hypertension,
`dyslipldemia. and metabolic syndrome. are up to 4 times higher in patients with schizophrenia than
`in the general population (Table 13.2933
`
`
`I Cardiovascular
`Prevalence in
`Preyalence i."
`.
`.
`. Risk Factors
`General Popuiation
`Schizophrenia
`Relative Risk (RRY
`F'o|:ii.ilatii:in29
`t Obesity
`34%”
`45%-55%
`1.5-2
`
`Diabetes
`
`1 Smoking
`t Hypertension
`: Dyslipidemia
`
`8%31
`
`21%3‘
`24%“
`16%32
`
`10%-15%
`
`50%-80%
`19%-58%
`25%-69%
`
`
`
`
`
`1-3.5
`
`2‘4
`1-2
`1-4
`
`1-2
`
`Metabolic syndrome
`
`34%33
`
`37%-63%
`
`'RelaliveiiskiRRFEiieriskoian eventreialivelo exposure; value aboveiiiidicaiesincreased rlsli.
`
`I
`
`I H
`
`The term “metabolic syndrome" refers to a group of abnormalities that is widely considered to be
`a precursor of diabetes and CVD. Metabolic syndrome can be constituted by changes in several
`cardiornetaboiic risk categories, including elevated fasting blood glucose. altered lipid profile,
`elevated blood pressure, being overweight or obese. and central adiposity. Patients with
`schizophrenia may be more susceptible to changes in these parameters than the general population
`and. therefore. may have a higher risk of metabolic syndrome and cardiovascular i:oniorbii:lities.3“-35
`
`According to a meta-analysis including over 25.000 patients with schizophrenia. the rate of
`metabolic syndrome in these patients approached 50%. compared with 33% in the general
`population.36 Additionally. atypical antipsychotic medications are associated with changes in
`metabolic parameters.37-33 Other contributing factors that may affect metabolic risk in patients
`with schizophrenia are that they receive less frequent or no screening and fewer treatments for
`cardiometaboiic risk factors-.39-40
`
`in addition to the higher prevalence of CVD. schizophrenia is often associated with higher rates of
`comorbid mental illnesses as well as respiratory and infectious diseases.""-“*2
`
`Economic Suntan
`
`Onset of symptoms of schizophrenia frequentiy occurs during the most productive years of
`adulthood (males: late teens to early 205: females: 205 to eariy 305). Therefore. the disease can
`lead to substantial losses in productivity and increased costs to both the patient and society.2M3
`
`Schizophrenia has been shown to have a substantiai economic impact. In a 2005 study, overall
`spending on schizophrenia was estimated at $62.? biliion a year (2002 data; Figure '0.“
`
`indirect costs (losses resulting from decreased productivity] made up the largest portion of
`spending, amounting to an estimated total of 532.4 billion. of these. unemployment was the
`greatest cost, ioilowed by caregiver expenses. reduced productivity. and suicide.“4
`
`Direct healthcare-related costs. including long-term care. outpatient and inpatient care. and
`pharmacy expenses. accounted for the second largest proportion of spending. estimated at
`$22.7 billion.44 Direct non~healthcare costs. including law enforcement, homeless shelters.
`and research and training. accounted for an estimated $7.6 billion.“
`
`a
`
`31
`e.as
`
`a s§:
`
`$2
`
`LATUDA has not been shown or indicated to impact heaithcare costs
`in prospective, randomized. placebo-controlled trials.
`
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`E
`Cost
`Percentage
`3’ Long-term care
`$7.97
`3
`35%
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`EOutpatientcare
`1 $6.95
`‘
`31%
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`
`22%
`{Pharmacy cost
`E $5.04
`1
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`‘
`12%
`Einpatientcare
`I $2.76
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`i
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`Direct Non-Healthca re Costs
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`About two-thirds of patients with schizophrenia also suffer from diabetes. dyslipidemia, hypertension. and/or
`heart disease, adding substantially to the economic burden of their mental illness (Figure 8).“5 Approximately
`2 of 3 patients with schizophrenia have at leasti of 4 associated comoroidities.
`
` fl fir minimum coir
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`a For schizoplnnla and CDI‘IIWIIIEEI'I'
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`AnnualSpendingPerPerson{5)
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`5000
`
`4000
`
`3000
`
`2000
`
`1000
`
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`Schizophrenia + Diabetes I Schizophrenia + arsllpldomia' Mlzophrenia + firmnensin I Schizophrenia + Heart Disease I
`[N :81000]
`il'i = 19,000}
`in = 165.000]
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`[Pl =130.000}
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`Noio1Petsons with )1 comorhidity appeal in multiple categories and their expenses are douoie counted.
`'Cnrnartlid categories are iimited to diabetes. dyslinidemia, hypertension anti heart disease.
`=Costs of persons with dvslipiriemia should be treated with caution because relasive standard error (SE) is >30%.
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`Factors Associated With Ciinicai and Economic Burden
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`Two factors that often play a substantial roie in the high ciinical and economic costs associated with
`schizophrenia are hospitalization and treatment nonadherence.‘“"‘4a
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`A study of medical and pharmacy claims for the years 1998 to 2007 found that newly diagnosed
`patients {st year since diagnosis) had significantly higher medical expenses in their first year of
`treatment than those diagnosed for 3 or more years.46 Newly diagnosed patients were hospitalized
`twice as often {22.3% vs i2.4%; P<0.000i), spent an average of 2 more days in the hospital, and
`cost approximateiv 55000 more than chronic patientsflé
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`Nonadherence to treatment is an important contributor to relapse that increases the healthcare
`burden of schizophrenia. One study found that continuous treatment reduced the risk of relapse by
`about 70%.“
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`A study of 213 patients found that discontinuation of antipsychotic medication doubled the risk of
`rehospitalization within the first 3 months of hospital discharge.43
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`Patient-related. treatment-reiated, and environmental factors may all piay a contributing role in the
`nonaclherence of patients with schizophrenia {Tabie 212°
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`Lack ot family support
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`Patient- Related Factors
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`Environmentat
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`Psychosoaal Factors
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`Lack of insight about
`iliness severity
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`{Breakdown of
`therapeutic alliance
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`Misconceptions about the
`importance of treatment
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`in Figure 9.
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`Treatment-Related Factors
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`Lac“ ”f Efficacy
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`Side effects
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`LATUDA has not been shown or indicated to impact hospitalization rates or treatment adherence in
`prospective. randomized. piacebo-controiled trials.
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`Contiaoing Need for Additions! antipsychotics
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`The Clinical Antipsvchotic Trials of intervention Effectiveness (CATIE) Study compared the reiative
`effectiveness of one first-generation {typical} antipsvchotic (perphenazine) and 4 second-generation
`(atypical) antipsychotics (olanzapine. quetiapine. risperidone, and ziprasidone) for treatment oi
`patients with schizophrenia.”
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`The CATIE Study indicated that 74% (1063/1432) of patients discontinued antipsychotic treatment
`before the 18-month study endpoint. Analysis of the reasons for discontinuation indicated that over
`one-haif of patients discontinued treatment due to either lack of efficacy (32%) or being unable to
`tolerate the prescribed drug (20%).49 The reasons given for treatment intolerance are described
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`Reasons for lntolerability
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`Weight gain or metabolic effects
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`Extrapyramidal symptoms
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`E] Sedation
`Other effects
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`LAWN. was not avaiiabie at the lirhe the CATtE Study was
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`conducted and therefore is not included in this analysis.
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` eed
`p vchot
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`considerations When Choosing an antipsvchotic for Schizophrenia
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`Having a variety of avaiiable antipsychotic drugs allows for individuaiization of therapy for adult patients with
`schizophrenia. important considerations when choosing the appropriate antipsvchotic for each patient include the
`patient's past responses to treatment, medication side-effect profiles, patient preferences, route of administration.
`presence of comorbid medical conditions. and potential interactions with other prescribed r‘nedications.so
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`Summary of Schizophrenia
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`Schizophrenia is a serious chronic and disabling mental illness with a substantiai clinical burden that includes poor
`overall physical health and higher rates of comorbid mentai illnesses as wail as cardiovascutar, respiratory. and
`infectious diseases: ail of which can contribute to a reduced iife expectanch9-2o-37'33
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`Schizophrenia is associated with significant costs clue to lost productivity and other direct and indirect healthcare—
`and non-heaithcare-relateci expenses.43i4“
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`Treatment nonadherence can result in poorer outcomes and may contribute to increased medical costs. Lack of
`treatment etiicacv andfor poor tolerability and patient and environmental factors mayr also all contribute
`to nonadherence.”
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`Adoiescents age 13 to 1? are diagnosed with the same criteria as adults, but schizophrenia can be harder to
`recognize in this population.24 The clinicai severity. impact on development, and poor prognosis of aooiescent
`schizophrenia underscore the importance of eariv detection. prompt diagnosis. and efiective treatments25
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`LATUDA has not been shown or indicated to impact