双極性障害治療薬の開発動向：双極性うつ病の新しい治療法

Abstract

Overview

Introduction

Stimulated by sales of atypical antipsychotics for bipolar depression, and despite the launch of generic risperidone, the global bipolar disorder market will grow until 2011, when revenues will peak at $6.6 billion. The market will begin to decline thereafter owing to the launch of generic versions of the leading atypical antipsychotics, quetiapine, olanzapine, and ziprasidone from 2011 onwards.

Scope

• Analysis of patient potential, unmet needs and clinical trial design in bipolar disorder
• Overview of drugs in pre-registration, Phase III, II and I; with analysis of key companies involved in the market
• Detailed profiles of key compounds in development for use in bipolar disorder, with forecasts of drug revenues to 2015
• Discussion of indication expansion strategies and insight from key industry opinion leaders

Highlights

AstraZeneca will be the first company to bring an atypical antipsychotic to the bipolar depression market as a monotherapy, following demonstration of efficacy with quetiapine. Pfizer will maintain a strong schizophrenia franchise by releasing asenapine to buffer the loss in revenue due to genericization of ziprasidone.

Solvay/Wyeth/Lundbeck's bifeprunox will be the leading market entrant in terms of bipolar disorder specific sales revenue. These companies appear to be seeking initial license for bifeprunox in the bipolar depression indication, a tactic that will both increase the commercial viability of the drug and save time/money.

Despite the commercial success of Lamictal (lamotrigine) and Depakote (valproate), the late-stage bipolar disorder pipeline only includes one anticonvulsant class molecule, Novartis' licarbazepine.

Reasons to Purchase

• Understand unmet needs in the bipolar disorder market based on key opinion leader comments
• Benchmark key late-stage bipolar disorder compounds against current market leaders
• Assess the global (US, Japan, five major EU) sales forecasts of late-stage pipeline drugs; and examine their clinical and commercial potential

Table of Contents

• 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-ﾅsberg 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