Sumitomo Pharma Co.ltd. · TSE:4506
Sumitomo Pharma Co.ltd — Dainippon Sumitomo Pharma — Technical Presentation (June 2009)
65 slides from Sumitomo Pharma Co.ltd's technical presentation, Jun 12, 2009
Slide 1: Lurasidone Meeting
Lurasidone Meeting June 12, 2009 Dainippon Sumitomo Pharma Co., Ltd. 1
Slide 2: Lurasidone: Clinical Studies Summary
Lurasidone: Clinical Studies Summary Antony Loebel, MD Vice President, Clinical Development Dainippon Sumitomo Pharma America 2
Slide 3: Lurasidone Development Timeline
Lurasidone Development Timeline Schizophrenia Schizophrenia First Pre- Pre -NDA Pre-NDA First in in EOP Man EOP 22 FDA FDA Meeting Meeting Man Meeting (Japan) Meeting (Japan) Bipolar Bipolar Depression Depression Phase Phase 33 1990- 2000 2002 2004 2005 2006 2007 2008 2009 2010 2011 1995 Lurasidone
Slide 4: Problems with Current Antipsychotic Agents
Problems with Current Antipsychotic Agents Lack of efficacy EPS/akathisia Prolactin increase Metabolic syndrome • Weight gain • Lipid increase • Diabetes QTc prolongation Sedation Poor functioning Reduced adherence to treatment 4
Slide 5: ADA/APA Consensus Statement on Antipsychotic Drugs and Obesity and Diabetes
ADA/APA Consensus Statement on Antipsychotic Drugs and Obesity and Diabetes Drug Weight Gain Diabetes Risk Dyslipidemia clozapine +++ + + olanzapine +++ + + risperidone ++ D D quetiapine ++ D D aripiprazole* +/- – – ziprasidone* +/- – – + = increased effect; - = no effect; D = discrepant results. *N
Slide 6: CATIE Schizophrenia Study: Time to Discontinuation
CATIE Schizophrenia Study: Time to Discontinuation for Any Cause Olanzapine (n=330) Risperidone (n=333) 1.0 Perphenazine (n=257) Quetiapine (n=329) 0.9 Ziprasidone (n=183) Proportion of Patients Continuing Treatment 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 3 6 9 12 15 18 Time to Discontinuation for Any
Slide 7: Psychiatrists Perceive the Greatest Unmet Needs in Schizophrenia and Bipolar Disorder
Psychiatrists Perceive the Greatest Unmet Needs in the Treatment of Schizophrenia and Bipolar Disorder to Involve Better/More Consistent Efficacy Balanced with Tolerable Side Effects Unmet Needs Schizophrenia Bipolar Disorder Uniform effectiveness (balanced with side More uniformly effective for
Slide 8: Receptor Binding Profiles: Lurasidone and Other Agents
Receptor Binding Profiles: Lurasidone and Other Agents Binding Affinities (Ki; nM) Lurasidone Risp Olanz Quet Zip Aripip Cloz D2 Antipsychotic 1.7 2.9 14 200 3 3.3 110 5-HT2A Antipsychotic/ 2.0 0.2 5.8 340 0.3 34 9.2 Attenuate EPS 5-HT1A Mood/Cognition 6.8 260 2700 320 8.5 2.1 120 5-HT7 Mood/Cogniti
Slide 9: 5-HT7 Receptor Autoradiography in Rat
5-HT7 Receptor Autoradiography in Rat Lurasidone Dose-Dependently Competes with [3H]SB-269970 Binding Total Non Specific Hi Th Hy Am Lurasidone 1 nM Lurasidone 10 nM Lurasidone 100 nM Lurasidone 1000 nM Am-Amygdala Hy-Hypothalamus Th-Thalamus Hi-Hippocampus 9
Slide 10: Lurasidone reverses MK-801-induced impairment of learning and memory (publication)
Available online at www.sciencedirect.com —e_—— “*5* ScienceDirect e European Journal of Pharmacology 572 (2007) 160-170 www.elsevier.com locate/ejphar Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance t
Slide 11: Lurasidone Reverses MK-801 Induced Learning & Memory Impairment
Lurasidone Reverses MK-801 Induced Learning & Memory Impairment 1 day later Inescapable shock 1 day later 1 day later + Lurasidone 11
Slide 12: Lurasidone Phase 2 Studies
Lurasidone Phase 2 Studies DSM-IV schizophrenia, requiring hospitalization 6-week, randomized, double-blind, placebo-controlled All studies involved US sites only Primary end point: BPRS derived from PANSS (BPRSd) Hospitalization required for 2-4 weeks 12
Slide 13: Study 006: PANSS Total Score
Study 006: PANSS Total Score (ITT-LOCF) Weeks 0 1 2 3 4 5 6 0 -2 Mean Change from Baseline -4 -6 -8 -10 -12 † -14 -16 * -18 * ** -20 Placebo (n=49) Lurasidone 40 mg (n=49) Lurasidone 120 mg (n=47) †p=0.06 *p≤0.05; **p=0.01 Ogasa et al. ICOSR 2003 13
Slide 14: Study 196: PANSS Total Score
Study 196: PANSS Total Score (ITT-LOCF) Weeks 0 Day 3 1 2 3 4 5 6 0 -2 Mean Change from Baseline -4 -6 * -8 -10 * -12 * -14 * * * * -16 Placebo (n=90) Lurasidone 80 mg (n=90) *p≤0.01 Nakamura M et al. J Clin Psych, 2009 14
Slide 15: J Clin Psychiatry June 2, 2009, e1-e8
J Clin Psychatry June 2, 2009, e1-e8 15
Slide 16: Depressive Symptom Change: Phase 2 Data
Depressive Symptom Change: Phase 2 Data Studies 006, 196 Study 196 PANSS MADRS Anxiety/Depression Lurasidone Anxiety Depression Placebo 80mg 0.0 0 Mean Change from Baseline Mean Change from Baseline n=135 n=181 n=135 n=181 n=83 n=86 -1 -0.5 -2 * -3 * * -1.0 -4 Baseline: Placebo 14.5, Lurasidone 14.2
Slide 17: PANSS Cognitive Subscale
PANSS Cognitive Subscale Study 196 0 n=90 n=90 -0.5 -0.5 Mean Change Plac e bo -1 Lu r asido n e -1.5 -2 -2.1 -2.5 p = 0.0015 Nakamura M et al. J Clin Psych, 2009 17
Slide 18: Simpson Angus Scale: Pooled Phase 2 Studies
Simpson Angus Scale (SAS): Pooled Phase 2 Studies* 2.5 2.0 Mean Change 1.5 1.24 1.0 0.49 0.5 0.23 0.09 -0.05 0.04 0.0 -0.5 Placebo Lurasidone Lurasidone Lurasidone Lurasidone Haloperidol 20mg 40mg 80mg 120mg 10mg n=209 n=71 n=114 n=159 n=48 n=72 *Studies 006, 049, 196 SAS scored 0-5 on 10 items for
Slide 19: Barnes Akathisia Rating Scale: Pooled Phase 2 Studies
Barnes Akathisia Rating Scale (BARS): Pooled Phase 2 Studies* 2.0 1.5 Mean Change 1.0 0.58 0.5 0.31 0.12 0.16 0.0 -0.04 -0.06 -0.5 Placebo Lurasidone Lurasidone Lurasidone Lurasidone Haloperidol 20mg 40mg 80mg 120mg 10mg n=210 n=71 n=114 n=160 n=48 n=72 *Studies 006, 049, 196 BAS scored 0-5 on Globa
Slide 20: Serum Prolactin: Pooled Phase 2 Studies
Serum Prolactin: Pooled Phase 2 Studies* 10 8.5 Median Change (ng/mL) 8 6 4 2 1.4 n=353 n=62 0 n=187 -2 -1.4 Placebo Lurasidone Haloperidol *Studies 006, 049, 196 20
Slide 21: CATIE Schizophrenia Study: Prolactin
CATIE Schizophrenia Study: Prolactin 20.0 Mean change from Baseline (ng/dL) 15.4 n=262 10.0 0.4 0.0 n=143 n=268 n=286 n=212 -4.5 -6.1 -10.0 -9.3 -20.0 Ziprasidone Risperidone Quetiapine Olanzapine Perphenazine Ziprasidone Olanzapine Mean Modal Dose Ziprasidone 112.8 mg/d Risperidone 3.9 mg/d Quetiap
Slide 22: Weight Gain: Pooled Phase 2 Studies
Weight Gain: Pooled Phase 2 Studies* Mean Change (kg) 2.0 1.5 1.0 0.46 0.5 0.16 0.10 n=208 n=387 n=71 0.0 Placebo Lurasidone Haloperidol *Studies 006, 049, 196 22
Slide 23: Estimated Mean Weight Gain with Antipsychotics
Estimated Mean Weight Gain at 10 Weeks with Antipsychotics 6 Conventional Antipsychotics Mean Change in Body Weight (kg) 5 Second-generation Antipsychotics 4 3 2 1 0 –1 –2 –3 e e e e ne ol ne e e e o on in on zin in in ol eb rid do pi az nd ap az ri d id ac na za pe in rid m oz as rt i Pl e an he ol
Slide 24: Lipid Profile: Pooled Phase 2 Studies
Lipid Profile: Pooled Phase 2 Studies# Cholesterol HDL* LDL* Triglycerides 0 -5 Mean Change (mg/dL) -10 -15 -20 -25 -30 n=192/381 n=78/76 n=72/70 n=192/381 Placebo Lurasidone #Studies 006, 049 and 196 *Not measured in study 049 Fasting measures obtained per protocol 24
Slide 25: CATIE Schizophrenia Study: Triglycerides
CATIE Schizophrenia Study: Triglycerides Mean Change from Baseline (mg/dL) 42.9 19.2 8.3 n=262 n=268 n=286 n=212 n=143 -2.6 -18.1 Ziprasidone Risperidone Quetiapine Olanzapine Perphenazine Mean Modal Dose Ziprasidone 112.8 mg/d Risperidone 3.9 mg/d Quetiapine 543.4 mg/d Olanzapine 20.1 mg/d Perphena
Slide 26: PEARL 1: Phase 3 Trial in Acute Schizophrenia
A Randomized, Double-Blind Study Comparing 3 Fixed Doses of Lurasidone to Placebo in Patients With Acute Schizophrenia: A Phase 3 Trial Study D1050229 (PEARL 1) 26
Slide 27: PEARL 1: Study Design
PEARL 1: Study Design Open-Label Double-Blind Phase Extension Phase Lurasidone Lurasidone 40 40 mg/d mg/d n=120 n=120 Lurasidone Lurasidone 80 80 mg/d mg/d Screening Baseline n=120 n=120 Lurasidone Lurasidone 40-120 mg/d 40-120 mg/d Lurasidone Lurasidone 120 120 mg/d mg/d n=120 n=120 Placebo Placebo
Slide 28: Key Entry Criteria
Key Entry Criteria DSM-IV schizophrenia • Acute exacerbation ≤2 months • ≤2 weeks hospitalization prior to screening • No significant improvement between screening and baseline Age 18-75 yrs Baseline Assessments • PANSS score ≥80; ≥4 (moderate) on at least 2 positive psychotic items • CGI-S ≥4
Slide 29: Efficacy Endpoints
Efficacy Endpoints Primary endpoint • Baseline to 6-week/endpoint change in PANSS Total Score, using mixed model repeated measures (MMRM) analysis adjusted by Hommel procedure for multiple comparisons (dose/endpoints) • ANCOVA LOCF used for sensitivity analysis Key secondary endpoint • CGI-S chang
Slide 30: PANSS Total (MMRM)
PANSS Total (MMRM) Wk 6 Baseline Day 4 Wk 1 Wk 2 Wk 3 Wk 4 Wk 5 Endpoint 0 LS Mean Change from Baseline -5 -10 * -15 * * 0.031 * 0.018 -20 * 0.017 * 0.010 * -25 0.011 Placebo (n=124) 40 mg Lurasidone (n=118) 80 mg Lurasidone (n=123) 120 mg Lurasidone (n=121) 30
Slide 31: PEARL 1: PANSS Total ≥30% Responder Analysis
PEARL 1: PANSS Total ≥30% Responder Analysis 70% P=0.028 p=0.058 * † Percentage of Subjects 60% 52% 50% 50% 46% 40% 38% 30% 20% 10% n=122 n=119 n=124 n=124 0% Lur 40 mg/d Lur 80 mg/d Lur 120 mg/d Placebo 31
Slide 32: PANSS Total: Per Protocol Population
PANSS Total: Per Protocol Population Lur 40 mg Lur 80 mg Lur 120 mg Placebo 0 n=100 n=89 n=94 n=102 -5 LS Mean Change (LOCF) -10 -15 -20 -25 * n=19 * p=0.004 n=26 p=0.032 n=13 n=29 -30 32
Slide 33: PANSS Positive Subscale (MMRM)
PANSS Positive Subscale (MMRM) Wk 6 Baseline Day 4 Wk 1 Wk 2 Wk 3 Wk 4 Wk 5 Endpoint 0 LS Mean Change from Baseline * ** ** * ** -5 * ** * ** * ** * ** * ** ** ** * ** * ** * ** -10 Placebo (n=124) 40 mg Lurasidone (n=118) *p<0.05 **p<0.01 80 mg Lurasidone (n=123) 120 mg Lurasidone (n=121) ***p<0.00
Slide 34: CGI-S (MMRM)
CGI-S (MMRM) Wk 6 Baseline Day 4 Wk 1 Wk 2 Wk 3 Wk 4 Wk 5 Endpoint 0.0 LS Mean Change from Baseline -0.3 -0.6 * 0.025 -0.9 * * 0.048 0.029 * 0.029 -1.2 * 0.009 * 0.006 -1.5 * 0.005 Placebo (n=124) 40 mg Lurasidone (n=122) 80 mg Lurasidone (n=119) 120 mg Lurasidone (n=124) 34
Slide 35: PEARL 1: Weight Change (LOCF)
PEARL 1: Weight Change (LOCF) 1.5 Median Change from Baseline (kg) 1.0 0.5 0.3 0.0 n=364 0.0 Lurasidone Placebo (N=124) 35
Slide 36: PEARL 1: Simpson Angus Scale (SAS)
PEARL 1: Simpson Angus Scale (SAS) 0.20 0.15 LS Mean Change 0.10 0.06 0.05 0.03 0.01 n=124 0.00 n=122 n=119 n=124 -0.01 -0.05 Lur 40 mg/d Lur 80 mg/d Lur 120 mg/d Placebo SAS scored 0-5 on 9 items for max possible score of 45 36
Slide 37: PEARL 1: Barnes Akathisia Rating Scale
PEARL 1: Barnes Akathisia Rating Scale (BAS) Global Clinical Assessment 1.0 LS Mean Change 0.5 0.3 0.1 0.1 0.0 0.0 Lur 40 mg/d Lur 80 mg/d Lur 120 mg/d Placebo n=124 n=122 n=119 n=124 BAS scored 0-5 on Global Clinical Assessment of akathisia for a maximum possible score of 5 37
Slide 38: PEARL 1: Serum Prolactin
PEARL 1: Serum Prolactin 3.0 Median Change (ng/mL) 2.5 2.0 1.5 1.0 0.70 0.5 0.35 n=361 n=122 0.0 Lurasidone Placebo 38
Slide 39: PEARL 1: Lipid Profile
PEARL 1: Lipid Profile Cholesterol HDL LDL Triglycerides 0 Median Change (mg/dL) -2 -4 -6 -8 -10 -12 -14 n=108/343 n=108/343 n=108/343 n=108/343 Placebo Lurasidone LOCF endpoint values; fasting per protocol; includes all subjects 39
Slide 40: PEARL 1: QTcF Interval Change (LOCF)
PEARL 1: QTcF Interval Change (LOCF) 10.0 8.0 Mean Change (msec) 6.0 4.0 1.9 2.1 1.8 2.0 1.2 n=120 n=117 n=122 n=120 0.0 Lur 40 mg/d Lur 80 mg/d Lur 120 mg/d Placebo 40
Slide 41: Treatment-Emergent Adverse Event Rates
Treatment-Emergent Adverse Event Rates (Incidence ≥10%) Phase 2 and 3 Data Studies 006/049/196/PEARL 1 6.2% Placebo (n=339) 11.2% Lurasidone 40 mg (n=241) Sedation 12.8% Lurasidone 80 mg (n=282) 11.6% Lurasidone 120 mg (n=173) 6.5% 10.8% Nausea 12.8% 6.5% 4.7% 8.7% Somnolence 10.6% 13.3% 4.1% 11.2%
Slide 42: Lurasidone Efficacy: Summary
Lurasidone Efficacy: Summary Consistent efficacy 40, 80 and 120 mg/d shown effective across 3 placebo-controlled trials Rapid onset (day 3 or 4) with subsequent sustained improvement noted in placebo-controlled trials Potential for improvement of cognitive deficits, based on preclinical and cl
Slide 43: Lurasidone Safety: Summary
Lurasidone Safety: Summary Lurasidone is well tolerated Low rates of EPS and akathisia Minimal prolactin change Neutral effects on weight, lipids and glucose Modest change in QTc interval Self-reported AEs are generally mild and transient Potential for Ongoing Adherence to Treatment 43
Slide 44: Lurasidone Development Program
Lurasidone Development Program 44
Slide 45: PEARL 1 and 2 Trials: Lurasidone in Acute Schizophrenia
PEARL 1 and 2 Trials: Lurasidone in Acute Schizophrenia Lurasidone Lurasidone 40 40 mg mg Lurasidone Lurasidone 80 80 mg mg Study Study 229 229 Lurasidone Lurasidone 40- 40-120 mg 40-120 mg Lurasidone Lurasidone 120 120 mg mg PEARL PEARL #1 #1 Open-label, 2 years Placebo Placebo Double-blind, 6 week
Slide 46: PEARL 3: Lurasidone in Acute Schizophrenia
PEARL 3: Lurasidone in Acute Schizophrenia Lurasidone Lurasidone 80 80 mg mg Studies Studies Lurasidone Lurasidone 160 160 mg mg Lurasidone Lurasidone 40- 40-160 mg 40-160 mg 233/234 233/234 Quetiapine Quetiapine XR XR 600 600 mg mg Quetiapine PEARL PEARL #3 #3 Quetiapine XR XR 200- 200-800 mg 200-8
Slide 47: Long-Term Safety Study With Cognitive Sub-Study
Long-Term Safety Study With Cognitive Sub-Study Open-Label Double-Blind Phase Continuation Phase Lurasidone Lurasidone 40 -120mg/d 40-120mg/d N= 400(200 for N=400(200 for sub -study) sub-study) Screening Screening Baseline Baseline Lurasidone Lurasidone 40-120mg/d 40-120mg/d Risperidone Risperidone
Slide 48: Atypical Use Has and Will Continue to Expand
Atypical Use Has and Will Continue to Expand Schizophrenia Bipolar Depression Treatment- Acute Bipolar Depression/ Maintenance Resistant Mania Depression Anxiety Depression Atypicals Mood Stabilizers Antidepressants 48
Slide 49: PREVAIL: Lurasidone in Bipolar Depression
PREVAIL: Lurasidone in Bipolar Depression 49
Slide 50: PREVAIL Add-On and Monotherapy Designs
PREVAIL Add-On Design (Study 235) PREVAIL Monotherapy Design (Study 236) Double-Blind Phase （Study 235） Lurasidone Lurasidone 20 -120 mg/d 20-120 mg/d ++ Lithium Lithium or or Valproate Baseline Valproate Baseline PREVAIL PREVAIL Screening Screening Extension Extension Placebo Study Study 3-28 days
Slide 51: Lurasidone Commercial Overview
Lurasidone Commercial Overview Joseph Yen Lin Vice President, Marketing Dainippon Sumitomo Pharma America 51
Slide 52: Agenda
Agenda I. Market and Disease State Overview II. Competitive Landscape 52
Slide 53: Market Overview: Overall Growth
Market Overview Overall Growth The atypical antipsychotic market is large and continues to grow at a robust rate +11.0% $14 +12.4% $14.1B +11.9% $12 +8.6% $12.7B $11.3B Sales ($Billions) $10 $10.1B $8 $9.3B $6 $4 $2 $0 2004 2005 2006 2007 2008 Source: IMS NSP Data, 2004-2008 53
Slide 54: Market Overview: Growth by Diagnosis
Market Overview Growth by Diagnosis Growth in the atypical antipsychotic category is being driven by use in bipolar disorder and schizophrenia $14.1B $14 $12.7B $11.3B Bipolar $12 $5.0 Disorder $10.1B $9.3B $4.4 Sales ($Billions) $10 $3.4 $2.6 $8 $2.3 $3.3 Schizophrenia $2.8 $2.2 $2.8 $6 $2.1 $1.3 D
Slide 55: Schizophrenia Disease State Overview: Patient Flow
Schizophrenia Disease State Overview Patient Flow U.S. lifetime prevalence of Origination schizophrenia is 1%; approximately 2.5 million affected Diagnosis/ Evaluation High rates of diagnosis (80%) and treatment (85%) Atypical antipsychotics considered Treatment the gold standard for schizophr
Slide 56: Schizophrenia Disease State Overview: Landmark CATIE Trial
Schizophrenia Disease State Overview Landmark CATIE Trial Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia Jeffrey A. Lieberman, M.D., T. Scott Stroup, M.D., M.P.H., Joseph P. McEvoy, M.D., Marvin S. Swartz, M.D., Robert A. Rosenheck, M.D., Diana O. Perkins, M.D., M.P.H.,
Slide 57: Bipolar Disease State Overview: Patient Flow
Bipolar Disease State Overview Patient Flow U.S. lifetime prevalence of bipolar Origination disorder is 2.6%; over 6 million affected Diagnosis/ Relatively lower rates of diagnosis Evaluation (45%) and treatment (80%) as compared to schizophrenia Multiple agents currently used in Treatment tre
Slide 58: Key Takeaways
Key Takeaways Opportunities Challenges Large, growing market for atypical antipsychotics High rate of dissatisfaction and switch; need for new treatment options Increasing use for the treatment of bipolar disorder is a significant driver of atypical antipsychotic market growth 58
Slide 59: Agenda
Agenda I. Market and Disease State Overview II. Competitive Landscape 59
Slide 60: Atypical Antipsychotic Market: Current Competitive Environment
Atypical Antipsychotic Market Current Competitive Environment Seroquel is the clear market leader; impact of generic risperidone not yet evident 40% 35% SEROQUEL 30% TRx Share 25% RISPERIDONE 20% 15% ABILIFY ZYPREXA 10% GEODON 5% CLOZARIL INVEGA 0% RIS CONSTA 03 l-0 3 04 l-0 4 05 l-0 5 06 l-0 6 07 l
Slide 61: Atypical Antipsychotic Market: Perceptual Mapping in Schizophrenia
Atypical Antipsychotic Market Perceptual Mapping in Schizophrenia Cognitive Functioning Better-Tolerated New product Medications (i.e. opportunity limited weight gain, Safety/Tolerability metabolic issues); Less Efficacious More Efficacious Medications; Less Well-tolerated (i.e. weight gain, metabol
Slide 62: APS Market Evolution: New Competitors, Generic Entries
APS Market Evolution: New Competitors, Generic Entries New Competitors Saphris (asenapine) Up to 3 new competitors Fanapt Serdolect within the next 12 months (iloperidone) (sertindole) 2009 2010 2011 2012 2013 2014 Generic Entries Generic Generic Large brands turning Olanzapine Paliperidone generic
Slide 63: Antipsychotic Payer Mix
Antipsychotic Payer Mix Public and private payers likely to increase control over utilization of branded products when more generics become available Dual Eligibles 7% Medicare Part D Medicaid 17% 23% Manage access through preferred drug lists (PDLs); Manage access through manufacturers provide tier
Slide 64: Key Takeaways
Key Takeaways Opportunities Challenges Large, growing market for Highly competitive market with atypical antipsychotics large brands High rate of dissatisfaction and New competitor launches switch; need for new treatment pending options Genericization of market Increasing use for the treatment
Slide 65: Disclaimer Regarding Forward-looking Statements
Disclaimer Regarding Forward- looking Statements The statements made in this presentation material are forward- looking statements based on management’s assumptions and beliefs in light of information available up to the day of announcement, and involve both known and unknown risks and uncertainties
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