PARKS General Collection
`
`RC321 Am3
`
`Per latest 6 months, o .e. Gen ........
`
`P ERIODICAL ROOM
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`Page 1 of 12
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`SLAYBACK EXHIBIT 1007
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`

`

`NOW APPROVED FOR YOUR ADULT PATIENTS
`BIPOLAR DEPRESSI
`W Lotudd
`(lurasidone HCI) tablets
`20mg |40mg|80mg|120mg
`
`
`
`Please see additional Important Safety Information, including Boxed Warnings, and Briet
`Summary of Prescribing Information on adjacent pages.
`1fl
`VfSUNOVION
`IAIUDA .tllti '2'? an! 'Ufllhh‘ll‘d trad-minim ol Damnation Slllllltultlu Ptmmm Cu ‘ ltrl
`Summon Phanuaueuticals inc l:- a U S snhsndmry nl Dam-pmm Sunntoum PilrlllIM Co , IIII
`1-7Ul3 Suriuvniu Pharmaceuticals Int: All righ:s resolved M3 LAI3'll
`I3
`
`Page 2 of 12
`
`SLAYBACK EXHIB]T 1007
`
`INDICATIONS
`
`LATUDA is indicated for the treatment of maior depressive episodes associated With
`bipolar | disorder {bipolar depressronl as monotherapy and as adjunctive therapy wrth lithium
`or valproate in adults.
`
`IMPORTANT SAFETY INFORMATION FOR lATUDA
`
`WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA—RELATED
`PSYCHOSIS; AND SUICIDAI. THOUGHTS AND BEHAVIDRS
`- Elderly patients with dementia-related psychosis treated with antipsychotic drugs are
`at an increased risk of death. LATUDA is not approved for use in patients with
`dementia-related psychosis.
`0 Antidepressants increased the risk of suicidal thoughts and behavior in children. adolescents,
`and young adults in short‘term studies. These studies did not show an increase in the risk of
`suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a
`reduction in risk with antidepressant use in patients aged 65 and older. In patients of all ages
`who are started an antidepressant therapy. monitor closely for worsening, and [or emergence
`of suicidal thoughts and behaviors. Advise families and caregivers ot the need for close
`observation and communication with the prescriber. LATUDA is not approved tor use
`in patients underthe age of 18 years.
`
`Page 2 of 12
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`SLAYBACK EXHIBIT 1007
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`

`

`IMPORTANT SAFETY INFORMATION ANO INDICATIONS FOR LATUDA
`
`WARNINGS:
`INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA(cid:173)
`RELATED PSYCHOSIS; AND SUICIDAL THOUGHTS AND BEHAVIORS
`
`• Elderly patients with dementia-related psychosis treated with
`antipsychotic drugs are at an increased risk of death. LATUDA is
`not approved for use in patients w ith dementia-related psychosis.
`• Antidepressants increased the risk of suicidal thoughts and
`behavior in children, adolescents, and young adults in short-term
`studies. These studies did not show an increase in the risk of
`suicidal thoughts and behavior with antidepressant use in patients
`over age 24; there was a reduction in risk with antidepressant use
`in patients aged 65 and older. In patients of all ages who are started
`on antidepressant therapy, monitor closely for worsening, and for
`emergence of suicidal thoughts and behaviors. Advise families and
`caregivers of the need for close observation and communication with
`the prescriber. LATUDA is not approved for use in patients under the
`age of 18 years.
`
`CONTRAINDICATIONS
`LATUDA is contraindicated in the following:
`• Known hypersensitivity to lurasidone HCI or any components m the
`formulation. Angioedema has been observed with lurasidone.
`• Strong CYP3A4 inhibitors (e.g., ketoconazole)
`• Strong CYP3A4 inducers (e.g., rifampin)
`
`WARNINGS AND PRECAUTIONS
`Cerebrovascular Adverse Reactions, Including Stroke: In placebo(cid:173)
`controlled trials w1th rispendone, anp1prazole, and olanzapine in elderly
`subjects with dementia, there was a h1gher mc1dence of cerebrovascular
`adverse react10ns (cerebrovascular accidents and transient ischemic
`attacks) includmg fatalities compared to placebo-treated subjects.
`LATUDA is not approved for the treatment of patients w1th
`dementia-related psychosis.
`Neuroleptic Malignant Syndrome (NMS): NMS, a potentially
`fatal symptom complex, has been reported w1th admin1strat10n of
`antipsychotic drugs, mcludmg LATUOA. NMS can cause hyperpyrexia,
`muscle rig1d1ty, altered mental status and ev1dence of autonomic
`mstabihty (irregular pulse or blood pressure, tachycardia, diaphoresis,
`and cardiac dysrhythmia). Additional s1gns may include elevated
`creatine phosphokmase, myoglobmuria (rhabdomyolysls), and acute
`renal failure. Management should mclude Immediate discontinuation of
`antipsychotic drugs and other drugs not essential to concurrent therapy,
`intensive symptomatic treatment and medical monitoring, and treatment
`of any concomitant senous medical problems.
`Tardive Dyskinesia (TO): TO 1s a syndrome consisting of potentially
`Irreversible, involuntary, dyskinetic movements that can develop in
`patients w1th antipsychotic drugs. There is no known treatment for
`established cases of TO, although the syndrome may remit, partially
`or completely, 1f antipsychotic treatment is withdrawn. The risk of
`developing TO and the likelihood that it will become ~rrevers1ble are
`believed to mcrease 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,
`alter relatively brief treatment periods at low doses. G1ven these
`considerations, LATUOA should be prescribed in a manner that is most
`likely to minimize the occurrence of TO. If signs and symptoms appear
`in a patient on LATUOA, drug d1scontmuation 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. Pati.ents w~o deve!op symptoms of hyperglycemia
`during treatment w1th atypical antlpsychotlcs 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.
`Oysliptdemta: Undesirable alterations in lipids have been observed
`in patients treated with atyp1cal anupsychotics.
`Wetght Gain: Weight gain has been observed with atypical
`antipsychotic use. Clinical monitoring of weight is recommended.
`
`Hyperprolactinemia: As with other drugs that a agonize dopamine 02 -i\
`
`receptors, LATUOA elevates prolactin levels. Ga ctorrhea, amenorrhea,
`gynecomastia, and Impotence have been reporte in patients receiving
`prolactm-elevating compounds.
`\J
`Leukopenia, Neutropenia, and Agranulocytosis: L kopeni
`neutropenia has been reported during treatment wi antipsychotic
`agents. Agranulocytosis (including fatal cases) has
`en repor\ed with
`other agents in the class. Patients with a preexisting ~Re~lood cell
`count (WBC) or a history of drug-induced leukopenia b\'U'u<$~18
`have their complete blood count (CBC) monitored freq
`nng the
`first few months of therapy, and LATUOA should be discontinued at the
`f1rst sign of a decline in WBC in the absence of other causative factors.
`Orthostatic Hypotension and Syncope: LATUOA may cause orthostatic
`hypotension. Orthostatic vital signs should be mon1tored in patients who
`are vulnerable to hypotension and in pat1ents w1th known cardiovascular
`disease or cerebrovascular disease.
`Seizures: LATUOA should be used cautiously in patients with a
`history of seizures or w1th cond1t1ons that lower seizure threshold
`(e.g., Alzhe1mer's dementia).
`Potential for Cognitive and Motor Impairment: Patients should be
`cautioned about operatmg 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.
`Appropnate care 1s advised when prescribing LATUOA for patients who
`will be experiencing conditions that may contnbute 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 su1c1de attempt is inherent in psychotic illness
`and close supervision of h1gh·nsk patients should accompany drug
`therapy. Prescnptions for LATUOA should be written for the smallest
`quantity of tablets consistent with good pat11nt management in order
`to reduce the nsk of overdose.
`Dysphagia: Esophageal dysmotllity and asp1rat1on 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 Alzhe1mer's dementia. LATUDA and other ant1psychot1c drugs
`should be used cautiously m patients at risk for aspiration pneumonia.
`
`ADVERSE REACTIONS
`Commonly observed adverse react1ons (<!5% incidence and at least twice
`the rate of placebo) for LATUDA:
`• Adult pat1ents w1th bipolar depression: akathisia, extrapyramidal
`symptoms, and somnolence
`• Adult patients with schizophrenia: somnolence, akathisia,
`extrapyramidal symptoms, and nausea
`
`INDICATIONS
`LATUDA is indicated for:
`• Treatment of major depressive episodes associated w1th bipolar I
`disorder (bipolar depression) as monotherapy and as adjunctive therapy
`with lithium or valproate in adults
`• Treatment of schizophrenia in adults
`
`Please see Brief Summary of Prescribing Information, including
`Boxed Warnings, on adjacent pages.
`
`Page 3 of 12
`
`SLAYBACK EXHIBIT 1007
`
`

`

`BRIEF SUMMARY OF FUll PRESCRIBING INFORMATION
`
`WARNINGS:
`INCREASED MORTALITY IN ElDERLY PATIENTS WITH DEMENTIA-RELATED
`PSYCHOSIS; AND SUICIDAL THOUGHTS AHO BEHAVIORS
`• Elderty patients with dementia-related psychosis
`treated with
`antipsychotic drugs are at an increased risk of death [see Warnings and
`Precautions (5. t )].
`• LAT\JOA Is not approved for use in patients with dementia-related
`psychosis [see Warnings and Precautions (5.1)].
`• Antidepressants increased the risk of suicidal thoughts and behavior
`In children, adolescents, and young adults in short-term studies. These
`studies did not show an Increase In the risk of suicidal thoughts and
`behavior with antidepressant use In patients over age 24; there was a
`reduction In risk with antidepressant use In patients aged 65 and older
`[see Warnings and Precautions (5.2)].
`• In patients of all ages who are started on antidepressant therapy,
`monltor closely for worsening, and for emergence of suicidal thoughts
`and behaviors. Advise families and caregivers of the need for close
`observation and communication with the prescriber [see Warnings and
`Precautions (5.2].
`
`Pooled analyses of stlort-term placebo-controlled trials of antidepressant drugs
`(SSRis and others) showed that these drugs increase the risk of suicidal thinking and
`behavior (SUICidality) m ch ldren, adolescents, and young adults (ages 18-24) with
`major depress1ve disorder (WOO) and other psychiatric disorders. Short-term studies
`did not show an increaSIJ ,r the risk of suicldality with antidepressants compared
`to placebo In adults beyo d 1ge 24; there was a reduction with antidepressants
`compared to placebo m ,... t: aged 65 and older.
`bo-controlled trials in children and adolescents with
`The pooled analyses o
`MOD, obseSSIVe CDmPL
`'>Order (OCD), or other psychiatric disorders included
`' 9 antidepressant drugs in over 4400 patients. The
`a total of 24 short-ter
`pooled analyses of p· ac
`, trolled trials in adults wrth MOO or other psychiatric
`95 short-term trials (median duration of 2 months)
`diSOrders Included a to•
`over 77,000 patients. There was considerable
`of 11 antidepressant d
`vanation 1n nsk of s ·
`rnong drugs, but a tendency toward an increase
`in the younger pat•'l
`most all drugs studied. There were differences
`In absolute nsk of st
`1cross the different indications, with the highest
`erences (drug vs. placebo), however, were relatiVe~
`Incidence In MOO. The
`;~o.
`stable w1th1n age stral a
`JSS indications. These risk differences (drug·placebo
`difference 1n the numbc
`•ses of suicidality per 1000 patients treated) are
`prOVIded In Table 1.
`Table 1
`
`1 INDICATIONS AND USAGE
`1.1 Schizophrenia
`LAT\JDA IS IndiCated for the treatment of patients w1th sch1zophrema.
`The effiCaCy of LATUDA 1n schllophrema was establiShed in five 6-week controlled
`studies of adult patients With schlloplvema [see Clmal Studi8S (14.1)).
`The effectrveness of LATUDA for longer-term use. that Is, for more than 6 weeks,
`has not beeo establlshed 111 controlled studies. Therefore. the physician who elects
`to use LATUDA for extended penods should penodiCally re-evaluate the long-term
`~ of the drug for the WldMdual pabent [see Dosage and Admlfvstrabon (2)).
`1.2 Depressive Episodes Associated with Bipolar I Disorder
`Monotherapy.LATUDA IS IndiCated as monotherapy for the treatment of patients With
`maJOf' depressrve ePISOdes 3SSOCiated With btpolar I diSOrder {bipolar depression).
`The efficacy of LATUDA was establiShed 1n a 6-week moootherapy study in adult
`pabents WTth btpotar depreSSIOfl {see ClmiCBI Studi8S (14. 2)).
`Adjunctive Therapy with Uthlum or ValproatB: LATUOA is indicated as adjUilC!Jve
`therapy WTth e~ther kthlum or valproate for the treatment of pabents wrth major
`depressNe epiSOdes assocaated With bipolar I diSorder (bipolar depression). The effiCacy
`of LATUOA was established in a 6-week study 111 adUt pabents With bipolar depresSIOn
`who were treated adjtn:bYely With ithun or~ {see Clncal Studies (14.2')].
`The effecbveness of LATUOA for longer-term use, that Is, for more than 6 weeks,
`has not beeo establiShed 1n controlled studies. Therefore, the physician who elects
`to use LATUOA for extended penods should penodiCally re-evaluate the long-term
`usefulness of the drug for the llldMdual patJent [see Dosage and AdmmtSfnition (2.2)).
`The efficacy of LATUOA 1n the treatment of mania associated WTth btpolar disorder
`has not beeo establiShed
`4 CONTRAINDICATIONS
`• Known hypersensitiVIty to luraSidone HCI or any components in the formulation.
`AngiOedema has been observed With IUf'asldone [see A/Nerse Reactions (6.1)).
`• Strong CYP3A4 inhibitors (e.g., ketoconazole, clantiYomycln, ntooaw, vonconazole,
`llllbefradli, etc.) {see Drug lnteracbons (1.1)/.
`• Strong CYP3A4 inducers (e.g., nfampm, avaSim•be. St. John's wort, phenytoin,
`carbamazepme, etc.) {see Orog lntetaetJons (1.1)}.
`5 WARNINGS AND PRECAUTIONS
`5.1 Increased Mortality In Elder1y Patients with Dementia-Related Psychosis
`Elderly patients With dementia-related psychosis treated with antipsychotic drugs are
`at an increased nsk of death. Analyses ol17 placebo·controlled trials (modal duration
`of 10 weeks), largely In patients taking atypical antipsychotic drugs, revealed a nsk of
`death il drug-treated patients of between 1.6- to 1.7-bmes the nsk of death in placebo(cid:173)
`treated patients. OvertheeotKSeof a typical10-weekcontrolled trial, the rate of death in
`aug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo
`group. Although the causes of death were varied, most of the deaths appeared to be
`!lither cardiovascular (e.g., heart falllre, sudden death) or 111fecbous (e.g., pneumonia)
`111 nature. Obsefvabonal studies suggest that, similar to atypical antipsychotic drugs,
`treatment wrth conventional antipsychotic drugs may increase mortality. The extent to
`which the findings of increased mortality in observational studies may be attributed
`to the antipsychotic drug as opposed to some characterlstic(s) of the patients is not
`clear. LATUOA is not approved lor the treatment of patients with dementia-related
`psychosis [see Boxed Waming}.
`5.2 Suicidal Thoughts and Behaviors in Adolescents and Young Adults
`Patients wrth major depressive disorder (MOD), both adult and pediatric, may
`experience worsening of their depression and/or the emergence of suicidal ideation
`and behavior (suicidahty) or unusual changes in behavior, whether or not they
`are taking antidepressant mediCations, and this nsk may persist until significant
`remission occurs. Suicide is a known risk of depression and certain other psychiatric
`disorders, and these disorders themselves are the strongest predictors of suicide.
`There has been a long-standing concern, however, that antidepressants may have
`arole in inducing worsening of depression and the emergence of sulcidality in certain
`patients during the earty phases of treatment.
`
`<18
`18·24
`
`2H4
`
`Drug-Placebo Oifferel1ce In Number ot cases Ill
`SUicldaily per 1000 Patien1s Tru1ed
`kmases C«npared to Placelio
`14 additional cases
`s additmal cases
`llecreas ~to Placelio
`1 fewer case
`&fewer cases
`1t1e pediatric trials. There were suicides 111 the adtit
`;ufficient to reach any conclusion about drug effect
`
`No suiCides occurred 1n any
`trials, but the number was rn
`on SUICide.
`It is unknown whether tile u•cidality rtsk extends to longer-term use, i.e., beyond
`several months. However, ttlere Is substantial evidence from placebo-controlled
`maintenance trials In adult.; w1th depression that the use of antidepressants can
`delay the recurrence of dep· •.!$~ on.
`All patients being treated with antidepressants for any Indication should
`be monitored appropriately and observed closely for clinlc~l ~n~~g,
`suicldality, and unusual changes In behavior, especially dunng the 1~i1ial
`few months of a course of drug therapy, or at times of dose changes, either
`Increases or decreases.
`The follow1ng symptoms ... ~~•ely, agitation, panic attacks, insomnia, irritability,
`(psychomoto_r re~~·
`hosbhty, aggres51Yeness. 1 npulsivlty, akathisia
`hypomama, and mama, have been reported in adult and pediatric patients belllQ
`treated With antidepressants for major depressive disorder as well as for other
`Indications, both psychiatric and nonpsychiatric. Although a causal link between the
`emergence of such symptoms and either the wor~ning of depression and/or the
`emergence of suicidal impulses has not been established, there 1s concern that such
`symptoms may represent precursors to emerging suicidality. .
`.
`.
`Consideration should be g1ven to changing the therapeutiC reg1men, includllQ
`possibly dlsconbRUing the mediCation, In patients whose depression is pe~stent!y
`worse, or who are experiellCing emergent suicidality or symptoms that m~ght be
`precursors to worsening depression or suic1dality, especially if these symptoms are
`severe, abrupt in onset, or were not part of the patient's presenting sy!"ptoms.
`Families and caregivers of patients being treated with antldep~nts
`for major depressive disorder or other Indications, both psychlatnc and
`nonpsychiatrlc, should be alerted about the need to monitor patients for
`the emergence of agitation, Irritability, unusual changes In behavior, and
`the other symptoms described above, as well as the emergence of suicidal
`thoughts and behaviors, and to report such symptoms immedi.ately to he.a.llh
`care providers. Such monitoring should include daily observation by fam1hes
`and caregivers. Prescriptions for LAT\JOA should be written for the smallest
`quantity of capsules consistent with good patient management, In order to
`reduce the risk of overdose.
`5.3 Cerebrovascular Adverse Reactions, Including Stroke In Elder1y Patients
`with Dementia-Related Psychosis
`In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly
`subjects with dementia, there was a higher incidence of cerebrovascular ad~se
`reactions (cerebrovascular accidents and transient ischemic attacks), 1nclud1ng
`fatalities, compared to placebo-treated subjects. LATUOA Is not approved ~ the
`treatment of patients with dementia-related psychosis {see also Boxed Wanvng and
`Wamings and Precautions (5.1)}.
`.
`5.4 Neuroleptic Malignant Syndrome
`A potentially fatal symptom complex sometimes referred to as NeuroleptiC
`Malignant Syndrome (NMS) has been reported in association with administration of
`antipsychotic drugs, including LATUDA.
`Clinical manifestations of NMS are 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
`
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`Page 4 of 12
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`SLAYBACK EXHIBIT 1007
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`elevated creatine phosphokinase, myoglobinuria (rhabdomyotysis), and acute
`renal failure.
`The dtagnostic evaluation of patients with this syndrome is complicated. It is
`important to exclude cases where the clinical presentation includes both serious
`medical illness (e.g., pneumoma, systemic infection) and untreated or inadequately
`treated extrapyramidal signs and symptoms (EPS). Other important considerations
`in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug
`fever, and primary central nervous system pathology.
`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. There is no
`general agreement about specific pharmacological treatment regimens for NMS.
`If a patient reqUires antipsychotic drug treatment after recovery from NMS,
`the potential reintroduction of drug therapy should be carefully considered. If
`reintroduced, the pattent should be carefully monitored, Since recurrences of NMS
`have been reported.
`5.5 Tardive Dyskinesia
`Tardive dyskinesia is a syndrome consisting of potentially trreverSlble, involuntary,
`dyskinetic movements that can develop in patients treated with antipsychotic
`drugs. Although the prevalence of the syndrome appears to be highest among the
`elderly, especially elderly women, it is impossible to rely upon prevalence estimates
`to predict, at the inception of anttpsychotic treatment, which patients are likely to
`develop the syndrome. Whether antipsychotic drug products dtffer in their potential
`to cause tardive dyskinesia ts unknown.
`The risk of developtng tardiVe dyskinesia and the likelihood that it will become
`irreversible are believed to increase as the duration of treatment and the total
`cumulative dose of anttpsychotic drugs administered to the patten! increase.
`However, the syndrome can develop, although much less commonly, after relatively
`bnef treatment periods at low doses.
`There is no known treatment for established cases of tardive dyskinesia,
`although the syndrome may remit, partially or completely, if antipsychotic treatment
`IS wtlhdrawn. Antipsychotic treatment, tlself, however, may suppress (or partially
`suppress) the signs and symptoms of the syndrome and thereby may possibly mask
`the underlying process. The effect that symptomatic suppression has upon the long(cid:173)
`term course of the syndrome is unknown.
`GIVen these considerations, LATUDA should be prescnbed in a manner that is
`most likely to mtnimlze the occurrence of tardive dyskinesia. Chronic antipsychotic
`treatment should generally be reserved for patents who suffer from a chronic illness
`that (1) is known to respond to antipsychotic drugs, and (2) for whom alternative,
`equally effective. but potentially less harmful treatments are not available or
`appropriate. In patients who do require chronic treatment, the smallest dose and the
`shortest duration of treatment producing a sattsfactory clinical response should be
`sought. The need for continued treatment should be reassessed periodically.
`If signs and symptoms of tardive dyskinesia appear in a patient on LATUDA,
`drug discontinuation should be constdered. However, some pabents may require
`treatment with LATUDA despite the presence of the syndrome.
`5.6 Metabolic Changes
`Atypical anttpsycholic drugs have been associated with metabolic changes that may
`increase cardiovascular/cerebrovascular risk. These metaboliC changes include
`hyperglycemia, dyshptdemta, and body wetght gain. Whtle all of the drugs in the
`class have been shown to produce some metabolic changes, each drug has its own
`spectfic nsk profile.
`Hyperq/ycemia and Diabetes Mellitus
`Hyperglycemia, In some cases extreme and associated Wtth ketoacidosis or
`hyperoSlmolar coma or death, has been reported in patients treated with atypical
`anlipsychotics. Assessment of the relationship between atypical anttpsychotic
`use and glucose abnormalities is complicated by the possibility of an Increased
`background risk of diabetes mellitus In patients with schlzophrema and the increasmg
`Incidence of dtabetes mellitus tn the general population. GIVen these confounders,
`the relationship between atypical antipsychotic use and hyperglycemia-related
`adverse events Is not completely understood. However, epidemiological studies
`suggest an increased risk of treatment-emergent hyperglycemia-related adverse
`events in patients treated wtth the atypical antipsychotics. Because LATUDA was
`not marketed at the ltme these studies were performed, it is not known if LATUDA is
`associated with this increased risk.
`Patients with an established diagnosis of diabetes mellttus who are started on
`atypical antipsychotics should be monitored regularly for worsening of glucose
`control. Patients wtth risk factors for dtabetes mellitus (e.g., obesity, family history
`of diabetes) who are starting treatment with atypical antipsychotics should undergo
`fasting blood glucose testtng at the beginmng of treatment and periodtcally during
`treatment. Any patient treated with atypical antipsycholics should be monitored
`for symptoms of hyperglycemia including polydipsia, polyuna, 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.
`Schizophrenia
`Pooled data from short-term, placebo-controlled schizophrenia studies are presented
`in Table 2.
`
`Serum Glucose
`
`Table 2: Change in Fasting Glucose in Schizophrenia Studies
`I
`I
`LATUDA
`I Placebo I 20 mglday I 40 mglday J SO mglday J 120 mgldayj_ 160 mg/day
`Mean Change from Baseline (mg/dl)
`I n:478 I n=508 I n=283 I n=113
`I n=680 I n=71
`I
`I ·0.6
`I +2.5
`I +2.5
`I +2.6 J
`·0.0
`·0.4
`Proportion of Patients with Shifts to~ 126 mgldl
`I 83\ I 11.7'fo I 12 7'fo I 6.8% I 10 O'fo I 5.6%
`
`SenMnGUose
`(6/108)
`(261260)
`132/472)
`(57/449)
`(7/60)
`(52/628)
`(~ 126 mg/dl)
`In the uncontrolled, longer-term schtzophrema studies (primarily open-label
`extension studies), LATUDA was associated with a mean change in glucose of
`+1.8 mg/dl at week 24 (n=355), +0.8 mg/dl at week 36 (n=299) and +2.3 mg/dl
`at week 52 (n=307).
`Bipolar Depression
`Monotherapy
`Data from the short-term, flexible-dose, placebo-controlled monotherapy bipolar
`depression study are presented in Table 3.
`Table 3: Change in Fasting Glucose in the Monotherapy Bipolar Depression
`Study
`
`I
`I
`Sen.m GU:ose I
`Serum Gklcn!e I
`
`80to120~-
`n=143
`
`+1.8
`
`L.ATUDA
`l
`I
`
`I
`
`l
`
`20 to 60 mglday
`Placebo
`n=140
`n=148
`Mean Change from Baseline (mg/d.)
`-o.s
`+18
`Proportion of Patients with Shifts to ~ 126 mg/dl
`6.4%
`43\
`22'111
`(91141)
`(61141)
`(31138)
`J
`~ 126mg.cl)
`Pabents were randomzed to llexibly dosed LATUDA 20 to 60 mg/day, LATlJOA 80 to 120 mgtday or placebo
`In the uncontrolled, open-label, longer-term btpolar depression study, patients who
`received LATUDA as monotherapy In the short-term study and continued in the
`longer-term study, had a mean change in glucose of +1.2 mg/dl at week 24 (n=129).
`AdjunctJve Therapy With I..Jttuum or Valproate
`Data from the short-term, flexible-dosed, placebo-controlled adjunctive therapy
`bipolar depreSSIOil studies are presented tn Table 4.
`Table 4: Change in Fasting Glucose in the Adjunctive Therapy Bipolar
`Depression Studies
`
`-r-
`J
`Placebo
`Mean Change from Basefine (mgldl.)
`J
`n=302
`·09
`____...L
`Proportion of Patients with Shifts ID ~ 126 mg/dl.
`13\
`1011o
`(41316)
`(31290)
`(~ 126 mgicl)
`_!
`Pabents were ~ to lledJiy dosed LATUOA 20 10 120 m¢ay or piDbo as ~ tllqy ~ Ill r.tlirn
`or~
`In the uncontrolled, open-label, longer-term bipolar depression study, patients who
`received LATUDA as adjuncbve therapy Wtth etther lithium or valproate in the short(cid:173)
`term study and continued in the longer-term study, had a mean change in glucose of
`+ 1.7 mg/dl at week 24 (n=88).
`{)yslloidem~a
`Undesirable alterations in lipids have been observed in patients treated wtlh atyptcal
`anttpsychotics.
`Schizophrenia
`Pooled data from short-term, placebo-controlled schizophrenia studtes are presented
`in Table 5.
`Table 5: Change in Fasting lipids in Schizophrenia Studies
`L.ATUDA
`40mglday 80mg/day
`20mglday
`Mean Change from Baseline (mg/dl)
`I n=466
`n=499
`n=71
`·12.3 L -5.7
`·62
`I
`·13.0
`·291
`·51
`Proportion of Patients with Shifts
`Tolal Cholestetol
`40'fo
`3.8\
`5.3\
`138\
`62'/o
`53\
`(8/581
`(41101)
`(301571)
`1231434)
`I'J/238)
`(25.402)
`~ 240mglcl)
`T ntJ!;erides
`7,0'fo
`6.3\
`10.5\
`101\
`(531526)
`(221209)
`(711001
`(4113791
`(2514001
`(71491
`~ 200mgtd.)
`In the uncontrolled, longer-term schizophrenia studies (pnmarlly open-label
`extension studies), LATUDA was associated wtth a mean change in total cholesterol
`
`.- -----r-
`
`I
`
`I
`Sen.m lime I
`Sen.m GlJcose I
`
`-
`
`L.ATUDA
`20 to 120 mglday
`
`n=319
`+12
`
`J
`120 mglday 160mglday
`
`n=268
`·38
`·3.1
`
`n=115
`-69
`·106
`
`I
`
`Placebo
`
`n=660
`Tota Cllolestem
`·58
`T~ ·134
`
`14 3% I 10.8\
`
`Page 5 of 12
`
`SLAYBACK EXHIBIT 1007
`
`

`

`and triglycerides of -3.8 (n=356) and -15.1 (n=357) mg/dl at week 24, -3.1 (n=303)
`and -4.8 (n=303) mg/dl at week 36 and -2.5 (n=307) and -6.9 (n=307) mg/dl at
`week 52, respectJvely.
`&polar ()epressJon
`Monotherapy
`Data from the short-term, flexible-dosed, placebo-controlled, moootherapy bipolar
`depression study are presented Ill Table 6.
`Table 6: Change In Fasting Upids In the Monotherapy Bipolar Depression
`Study
`!
`-
`
`UTUDA
`
`80 to 120 mg/day
`
`20 to 60 mg/day
`Placello
`Mean Qlangl fnlm ll&selnt (mglcl)
`11::147
`n:140
`t12
`·32
`t56
`+60
`l'lupor1lon Gl Patilnt1 with Sllfts
`TOCII ddlsllral
`44'4
`42\
`44'4
`(51114)
`(51113)
`(511181
`~240~
`48\
`101'4
`98'4
`T~
`(12/119)
`11211221
`~200~
`~
`l'llln wert rWidcnlzld to kxttr cbled lAJillo\ 20 to 60 ~. UTUOA 80 to 120 i1liYdaY or~
`In the oocontrolled, open-label, longer-term bipolar depressMlll study, patients who
`recetVed LA TUDA as monotherapy Ill the short-term and continued in the longer-term
`study had a mean change 111 total cholesterol and triglycendes of -0.5 (n= 130) and
`-10 (n=130) mg/dl at week 24, respecbvely.
`~ T1letiJpy with Uthium or Yaf~Wate
`Data from the short-term, flexible-dosed, placebo-controlled, adJunctive therapy
`bipolar depressMlll studies are presented Ill Table 7.
`Table 7: Change In Fasting Uplds In the Adjunctive Therapy Bipolar
`Depression Studies
`,..----
`
`Talal c:tiOiesi!rd
`T~
`
`n=144
`-46
`t04
`
`UTUDA
`20 1D 120 mg/day
`
`ToQI dlcllesllrol
`T~
`
`na321
`·31
`t46
`
`l'llclbo
`Mean Qlangl fnlm llaMIIIt (mgJcl)
`aa303
`·2.9
`-46
`Proportioi.C l'ltllnts with Sllfts
`54'4
`51'4
`TOCII~
`(1512761
`11~
`~ 240~
`8.6'4
`10.8\
`T~
`(2812601
`~ 200~
`12lll431
`1'-.a wn lllllbiiZid ID kxilly ~ UTOOA 20 1D 120 ~or piPIJo • ~ 111er1CIY With iltiU11
`or,._
`In the II1COillrolled, open-label, longer-term bipolar depressm study, patients who
`recerved LATUOA, asadjiJlctivetherapywrth eitherbttuum orvalproate 1n the short-term
`study and contnJed i'l the longer-term study, had a mean change in total cholesterol
`and triglycendes of -0.9 (n=88) and 5.3 (n=88) mg/dl at week 24, respectively.
`Weight Gain
`We1ght gam has been observed with atypical antipsychotic use. Clinical monitoring
`of weight is recommended.
`Schizophrenia
`Pooled data from short-term, placebo-controlled schizophrenia studies are
`presented in Table 8. The mean weight gain was 0.43 kg for LATUDA-treated patients
`compared to -0.02 kg for placebo-tr