[Report] Bipolar Disorder Pipeline Insight Market Research, Trends, Analysis TOC

ABOUT DATAMONITOR HEALTHCARE
- About the CNS pharmaceutical analysis team
CHAPTER 1 EXECUTIVE SUMMARY
- Scope of the analysis
- Datamonitor insight into the bipolar disorder market
  - Summary
- Datamonitor Pipeline Assessment Summary
CHAPTER 2 PATIENT POTENTIAL
- Definition of bipolar disorder
  - Characteristics of bipolar disorder phases
- Segmentation of bipolar disorder subtypes
  - Bipolar I disorder
  - Bipolar II disorder
  - Bipolar III disorder (cyclothymia)
- Epidemiology of bipolar disorder
  - Prevalence and diagnosis rate of bipolar disorder
    - Increased prevalence rate due to relaxing of inclusion criteria
    - Poor correct diagnosis rates leave room for market expansion
- Unmet needs in bipolar disorder
  - Unmet need 1: improved maintenance therapy
    - Improved prophylactic treatment the key to real patient benefit
- Unmet need 2: bipolar depression
  - Sufferers spend significantly longer in bipolar depression than mania
  - High suicide rate during depressive phase
  - Traditional antidepressants have limited efficacy
    - Unmet need 3: treatment non-compliance
    - Unmet need 4: side effects
    - Unmet need 5: onset of therapeutic action
- Etiology of bipolar disorder
  - Neurobiology of bipolar disorder
    - Dopamine hypothesis of schizophrenia and bipolar mania
    - Monoamine theory of major depression and bipolar depression
CHAPTER 3 R&D APPROACH
- Market overview
  - Current treatment paradigms for bipolar disorder
    - Treatment of manic episodes associated with bipolar disorder
    - Maintenance and prophylactic therapy
    - Treatment of bipolar depression
- Sales of antipsychotics generated approximately half the revenues associated with bipolar disorder pharmacotherapy
- Off-label use of antidepressants for bipolar disorder treatment
  - Classification of pipeline drugs seeking indication in bipolar disorder
    - Novel mood stabilizers
    - Anticonvulsants
    - Antipsychotics
- Pharmacological development of antipsychotics
- Mixed molecular targets of the current and pipeline atypical antipsychotics
- Increasing concentration on side-effect profile for the antipsychotic class of therapy
  - Clinical trial design in bipolar disorder
    - Young mania rating scale
    - Montgomery-Åsberg Depression Rating Scale
    - Hamilton Rating Scale for Depression
    - Positive and Negative Syndrome Scale
    - Problems associated with bipolar disorder clinical trial design
- Pipeline overview
  - Pipeline drugs in pre-registration
  - Pipeline drugs in Phase III clinical development
  - Pipeline drugs in Phase II clinical development
  - Pipeline drugs in Phase I clinical development
    - Lack of innovative and Phase I drugs found in the bipolar disorder pipeline
- Key companies involved in the bipolar disorder pipeline
  - Johnson & Johnson's bipolar disorder franchise will decline from 2008 onwards despite the launch of paliperidone
    - Generic incursion expected when key CNS products come off-patent
    - Follow-on antipsychotic may not be sufficiently differentiated
    - Off-label bipolar-specific sales of topiramate may deteriorate following negative trial results
- RepliGen are developing a novel intracellular mood stabilizer
  - RG-2417 (Uridine) a potential novel mood stabilizer
  - Previous failure to show statistically significant efficacy of secretin in schizophrenia
  - Phase I trial with RG-2133-another Uridine pro-drug
CHAPTER 4 ANTIPSYCHOTIC LATE-STAGE DRUG ANALYSIS & FORECASTS
- Overview of antipsychotic class of bipolar therapy
  - Pipeline summary
- Definition of current comparator therapy
  - US market leader status for Seroquel despite not being licensed for maintenance therapy
    - Sales of atypical antipsychotics are higher for bipolar disorder than schizophrenia in the US
- Short to medium-term sales unaffected by indication expansion
- Experience from prescribing for schizophrenia drove the bipolar atypical antipsychotic market
- Indication expansion may not be financially beneficial unless the right bipolar indication is sought
- Factors required for a pipeline antipsychotic to compete in the bipolar disorder market
- Market sales and forecast caveats
  - Seroquel for bipolar depression
- Profile
  - Drug overview: indication expansion into bipolar depression imminent
  - Clinical trial data
  - Clinical trial data and pharmacodynamic summary
  - Why would an atypical antipsychotic have therapeutic efficacy against bipolar depression?
- Patient potential
- Marketing factors
- Satisfaction of unmet needs
  - Unmet need 1: improved maintenance therapy
  - Unmet need 2: bipolar depression
  - Unmet need 3: treatment non-compliance
  - Unmet need 4: side effects
  - Unmet need 5: onset of therapeutic action
- Forecasts to 2015
  - Brief explanation of impacting factors
    - Datamonitor drug assessment summary
- Geodon for bipolar depression
  - Profile
  - Drug overview: indication expansion into bipolar depression
    - Clinical trial data
    - Clinical trial data and pharmacokinetic summary
- Patient potential
- Marketing factors
- Satisfaction of unmet needs
  - Unmet need 1: improved maintenance therapy
  - Unmet need 2: bipolar depression
  - Unmet need 3: treatment non-compliance
  - Unmet need 4: side effects
  - Unmet need 5: onset of therapeutic action
- Forecasts to 2015
  - Brief explanation of impacting factors
- Datamonitor drug assessment summary
  - Risperdal Consta
  - Profile
    - Drug overview: intramuscular sustained-release formulation of Risperdal
    - Clinical trial data
    - Clinical trial data and pharmacokinetic summary
- Patient potential
  - Significant off-label usage reduces the "new" patient population
  - Risperdal Consta will be competing with the oral formulations rather than IM formulations
- Marketing factors
  - Price is primary concern but sales revenue looks strong
  - Increased use of risperidone might have a positive effect on Risperdal Consta sales
  - J&J should target its marketing of Risperdal Consta towards treating severely manic patients
- Satisfaction of unmet needs
  - Unmet need 1: improved maintenance therapy
  - Unmet need 2: bipolar depression
  - Unmet need 3: treatment non-compliance
  - Unmet need 4: side effects
  - Unmet need 5: onset of therapeutic action
- Forecast to 2015
  - Brief explanation of impacting factors
- Datamonitor drug assessment summary
- Intramuscular Abilify
  - Profile
    - Drug overview: intramuscular version of Abilify for acute intervention
    - Clinical trial data
    - Clinical trial data and pharmacokinetic summary
- Patient potential
  - IM version may boost sales of oral Abilify as a first-line therapy
  - Abilify needs to demonstrate strong efficacy in a head-to-head study
  - Abilify's positive side-effect profile may not be a significant advantage in the acute setting
  - Abilify's lack of sedation may prove to be a disadvantage for acute mania treatment
- Marketing factors
  - How will Abilify IM be priced?
  - BMS/Otsuka should consider a long-acting IM version of Abilify
- Satisfaction of unmet needs
  - Unmet need 1: improved maintenance therapy
  - Unmet need 2: bipolar depression
  - Unmet need 3: treatment non-compliance
  - Unmet need 4: side effects
  - Unmet need 5: onset of therapeutic action
- Forecast to 2015
  - Brief explanation of impacting factors
- Datamonitor drug assessment summary
- Asenapine
  - Profile
    - Drug overview: "new" atypical antipsychotic
    - Clinical trial data
    - Clinical trial data and pharmacokinetic summary
- Patient potential
- Marketing factors
  - Pfizer bring a wealth of experience in marketing atypical antipsychotics to the table
  - Establishing a niche patient population for asenapine will be important for its commercial success in bipolar disorder
    - Delay in development may impact future sales estimates
- Satisfaction of unmet needs
  - Unmet need 1: improved maintenance therapy
  - Unmet need 2: bipolar depression
  - Unmet need 3: treatment non-compliance
  - Unmet need 4: side-effects
  - Unmet need 5: onset of therapeutic action
  - Forecast to 2015
    - Brief explanation of impacting factors
- Datamonitor drug assessment summary
- Bifeprunox
  - Profile
    - Drug overview: New atypical antipsychotic with similar mode of action to Abilify
    - Clinical trial data
    - Clinical trial data and pharmacokinetic summary
- Patient potential
  - Bifeprunox unlikely to be used for acute mania, but may have a niche in first-line maintenance therapy
- Marketing factors
  - Solvay's and Wyeth's experience in psychiatry and Lundbeck's launch of sertindole will provide a strong base for the commercialization of bifeprunox
    - Differentiation from Abilify may become a problem
    - Indication in bipolar depression could boost sales and save time/money
    - Key events which could impact the revenue growth of bifeprunox
- Satisfaction of unmet needs
  - Unmet need 1: improved maintenance therapy
  - Unmet need 2: bipolar depression
  - Unmet need 3: treatment non-compliance
  - Unmet need 4: side effects
  - Unmet need 5: onset of therapeutic action
- Forecast to 2015
  - Brief explanation of impacting factors
- Datamonitor drug assessment summary
- Paliperidone ER
  - Profile
    - Drug overview: metabolite of risperidone
    - Clinical trial data
    - Clinical trial data and pharmacokinetic summary
- Patient potential
  - Development of paliperidone IM for bipolar disorder could be a better strategy
- Marketing factors
  - Are active metabolites commercially viable?
  - Following Risperdal patent expiry-making the switch to paliperidone versus generic risperidone
- Satisfaction of unmet needs
  - Unmet need 1: improved maintenance therapy
  - Unmet need 2: bipolar depression
  - Unmet need 3: treatment non-compliance
  - Unmet need 4: side effects
  - Unmet need 5: onset of therapeutic action
- Forecast to 2015
  - Brief explanation of impacting factors
- Datamonitor drug assessment summary
CHAPTER 5 ANTICONVULSANT LATE-STAGE DRUG ANALYSIS & FORECASTS
- Overview for anticonvulsants
  - Pipeline summary
  - Definition of current comparator therapy
    - Anticonvulsant 'gold-standard': lamotrigine
- Licarbazepine
  - Profile
    - Drug overview: Metabolite of the anticonvulsant oxcarbazepine
    - Clinical trial data
- Patient potential
- Marketing factors
- Satisfaction of unmet needs
  - Unmet need 1: improved maintenance therapy
  - Unmet need 2: bipolar depression
  - Unmet need 3: treatment non-compliance
  - Unmet need 4: side effects
  - Unmet need 5: onset of therapeutic action
- Forecast to 2015
  - Brief explanation of impacting factors
CHAPTER 6 NOVEL MOOD STABILIZER LATE-STAGE DRUG ANALYSIS & FORECAST
- Overview for novel mood stabilizers
  - Pipeline summary
- Definition of current comparator therapy
  - Mood stabilizer 'gold-standard': lithium
- RG-2417 (Uridine)
  - Profile
    - Drug overview: Novel metabolism modulator
    - Clinical trial data
- Patient potential
- Marketing factors
- Satisfaction of unmet needs
- Forecast to 2015
- Memantine
  - Profile
    - Drug overview: NMDA receptor antagonist
    - Clinical trial data
- Patient potential
- Marketing factors
- Satisfaction of unmet needs
- Forecast to 2015
BIBLIOGRAPHY
- Journal articles and conference abstracts
- Websites
APPENDIX A
- Forecast revenues
- Competitive positioning analysis of pipeline bipolar disorder drugs
APPENDIX B
- Report Methodology
  - Definition of bipolar disorder market
  - Datamonitor forecast methodology
    - Product forecasts
    - Sales calculations
    - Definition of a standard unit
    - Japanese market data
- Additional information
- About Datamonitor
  - About Datamonitor Healthcare
  - Datamonitor Healthcare's therapy area capabilities
  - About the CNS analysis team
  - Disclaimer
- List of Tables
  - Table 1: Prevalence data overview of bipolar disorder in the US, Canada and Switzerland, 2006
  - Table 2: Neurophysiological consequences of reduction in dopamine level
  - Table 3: Young Mania Rating Scale
  - Table 4: Pipeline drugs in pre-registration for bipolar disorder, 2006
  - Table 5: Pipeline drugs in Phase III development for bipolar disorder, 2006
  - Table 6: Pipeline drugs in Phase II development for bipolar disorder, 2006
  - Table 7: Pipeline drugs in Phase I development for bipolar disorder, 2006
  - Table 8: Key antipsychotics in late-stage R&D pipeline for bipolar disorder, 2006
  - Table 9: Marketed bipolar disorder-indicated antipsychotics: key facts, 2006
  - Table 10: FDA approval in schizophrenia and bipolar disorder for atypical antipsychotics
  - Table 11: Binding characteristics of atypical antipsychotics (Ki)
  - Table 12: Factors impacting Seroquel's revenues , 2006-2015
  - Table 13: Geodon clinical trial program for bipolar depression and bipolar maintenance, 2006
  - Table 14: Factors impacting Geodon's revenues, 2006-15
  - Table 15: Price of different formulations of Risperdal ($), 2001-05
  - Table 16: Factors impacting Risperdal Consta's revenues, 2006-2015
  - Table 17: All-indication US sales revenues for the rapid-acting atypical antipsychotic IMs ($m), 2002-05
  - Table 18: Price points for the rapid-acting atypical antipsychotic IMs ($), 2004-06
  - Table 19: Factors impacting Abilify's revenues , 2006-2015
  - Table 20: Asenapine clinical trial program in bipolar disorder, 2006
  - Table 21: Binding characteristics of atypical antipsychotics (Ki)
  - Table 22: Factors impacting asenapine's revenues, 2006-15
  - Table 23: Bifeprunox clinical trial program in bipolar disorder, 2006
  - Table 24: Factors impacting bifeprunox's revenues 2006-15
  - Table 25: Paliperidone ER clinical trial program in bipolar disorder, 2006
  - Table 26: Factors impacting paliperidone's revenues, 2006-2015
  - Table 27: Anticonvulsants in late-stage R&D pipeline for bipolar disorder, 2006
  - Table 28: Licarbazepine clinical trial program for bipolar disorder, 2006
  - Table 29: Factors impacting licarbazepine's revenues, 2006-2015
  - Table 30: Novel mood stabilizers in the late-stage R&D pipeline for bipolar disorder, 2006
  - Table 31: Memantine clinical trial program for bipolar disorder, 2006
  - Table 32: Datamonitor's forecast bipolar disorder revenues of marketed and pipeline drugs across the US, EU and Japan ($m), 2006-2015
  - Table 33: Summary of commercial and research/clinical attractiveness of late-Phase drugs for bipolar disorder
  - Table 34: Diagnostic criteria for bipolar I disorders
  - Table 35: Diagnostic criteria for other types of bipolar disorders
- List of Figures
  - Figure 1: Bipolar disorder market forecast, 2006-15
  - Figure 2: Generic incursion on global bipolar disorder atypical antipsychotic market
  - Figure 3: Datamonitor drug assessment summary
  - Figure 4: Symptoms associated with the two primary phases of bipolar disorder
  - Figure 5: Cycles of bipolar disorder phase over time
  - Figure 6: Unmet needs in bipolar disorder, 2006
  - Figure 7: US bipolar disorder market revenues by drug class, 2002-05
  - Figure 8: Drug classes in development for the treatment of bipolar disorder, 2006
  - Figure 9: Antipsychotic market structure based on bipolar disorder-specific sales revenue in the seven major markets, 2005
  - Figure 10: US revenue split of antipsychotics between bipolar disorder, schizophrenia and all other indications, 2005
  - Figure 11: The US bipolar disorder specific quarterly sales revenue for atypical antipsychotics, 2003-05
  - Figure 12: US quarterly promotional spend on non-direct to customer advertising for atypical antipsychotics, 2003-05
  - Figure 13: BOLDER I clinical trial path for Seroquel
  - Figure 14: Datamonitor's forecast of bipolar-specific sales revenue for Seroquel across the seven major markets ($m), 2006-2015
  - Figure 15: Datamonitor's competitive positioning analysis of Seroquel for bipolar depression, 2006
  - Figure 16: Datamonitor's forecast of bipolar-specific sales revenue for Geodon across the seven major markets ($m), 2006-2015
  - Figure 17: Datamonitor's competitive positioning analysis of Geodon for bipolar disorder, 2006
  - Figure 18: Comparison of the proportion of US bipolar-specific sales for the two formulations of Risperdal, 2005
  - Figure 19: Bipolar-specific sales revenue for the two formulations of Risperdal in the US ($m), 2003-05
  - Figure 20: Datamonitor's forecast of bipolar-specific sales revenue for Risperdal Consta across the seven major markets ($m), 2006-2015
  - Figure 21: Datamonitor's competitive positioning analysis of Risperdal Consta for bipolar disorder, 2006
  - Figure 22: Datamonitor's forecast of bipolar-specific sales revenue for Abilify (oral and IM) across the seven major markets ($m), 2006-2015
  - Figure 23: Datamonitor's competitive positioning analysis of Abilify IM for bipolar disorder, 2006
  - Figure 24: Receptor affinity profiles for asenapine and risperidone
  - Figure 25: Datamonitor's forecast of bipolar-specific sales revenue for asenapine across the seven major markets ($m), 2006-2015
  - Figure 26: Datamonitor's competitive positioning analysis of asenapine for bipolar disorder, 2006
  - Figure 27: Datamonitor's forecast of bipolar-specific sales revenue for bifeprunox across the seven major markets ($m), 2006-2015
  - Figure 28: Datamonitor's competitive positioning analysis of bifeprunox for bipolar disorder, 2006
  - Figure 29: Paliperidone ER only meets one of the criteria for a commercially successful active metabolite
  - Figure 30: Datamonitor's forecast of bipolar-specific sales revenue for paliperidone ER across the seven major markets ($m), 2006-2015
  - Figure 31: Datamonitor's competitive positioning analysis of paliperidone for bipolar disorder, 2006
  - Figure 32: US revenue split of anticonvulsants between bipolar disorder and all other indications, 2005
  - Figure 33: US bipolar disorder-specific sales revenue for on- and off-label use of anticonvulsants, 2005
  - Figure 34: Licarbazepine meets two of the criteria for a commercially successful active metabolite
  - Figure 35: Datamonitor's forecast of bipolar-specific sales revenue for licarbazepine across the seven major markets ($m), 2006-2015

Pipeline Insight: Bipolar Disorder - New treatments for bipolar depression set to drive near-term growth

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