統合失調症治療薬市場の動向

Introduction

The global schizophrenia market will continue to grow until 2010, when revenues will reach $3.8 billion. However, despite the launch of numerous pipeline schizophrenia drugs, the market will begin to decline thereafter owing to the US launch of generic risperidone in 2007, followed by generic versions of olanzapine, quetiapine and ziprasidone from 2011 onwards.

Scope of this report

• Detailed pipeline analysis for key products in development for schizophrenia, plus drug sales forecasts to 2015
• Overview of patient potential, segmentation by indication and unmet needs in schizophrenia across the US, EU and Japan
• Benchmarking of key product and company attractiveness of late-phase pipeline products
• Detailed clinical trial information and opinions from key thought leaders

Research and analysis highlights

By 2015, prospective players can expect to face stiff competition from numerous generic atypical antipsychotics. Product differentiation through improved treatment of negative or cognitive symptoms, partial responders, as well as improved tolerability, and demonstration of cost-effectiveness are essential.

Current schizophrenia drug manufacturers are taking measures to buffer the erosion of their products by generics over the forecast period. Of the current players, Datamonitor forecasts that only Pfizer will maintain a strong schizophrenia franchise after the genericization of its marketed drug, with the remaining franchises expected to decline.

The potential of Organon/Pfizer's asenapine in treating negative symptoms will be a key therapeutic and commercial advantage, with the drug forecast to be the leading market entrant in terms of value by 2015. Lundbeck/Solvay/Wyeth's bifeprunox's will become the second highest new entrant in terms of value by 2015.

Key reasons to read this report

• Understand unmet needs in the schizophrenia market based on key opinion leader comments regarding both currently marketed and pipeline products
• Benchmark key late-stage schizophrenia compounds against current market leaders
• Assess the global sales forecasts of late-stage pipeline drugs for schizophrenia 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 schizophrenia market
  • Key metrics
• CHAPTER 2 PATIENT POTENTIAL
  • Etiology of schizophrenia
  • DSM-IV defined symptoms of schizophrenia
  • A - Characteristic symptoms
  • B - Social/occupational dysfunction
  • C - Duration
  • D - Schizoaffective and mood disorder exclusion
  • E - Substance/general medical condition exclusion
  • F - Relationship to a pervasive developmental disorder
  • Classification of schizophrenia
  • Epidemiology of schizophrenia
  • Schizophrenia affects 1% of the population
  • Comorbidities of schizophrenia
  • Anxiety is the most prevalent comorbidity of schizophrenia
  • Substance and alcohol abuse is frequently observed in schizophrenia
  • Depression affects a third of schizophrenia patients
  • Diagnosis rates of schizophrenia
  • Unmet needs in schizophrenia
  • Improving patient compliance is key
  • Lack of insight into schizophrenia, and the management thereof, are the most frequent reasons for patient noncompliance
  • Increased public and physician awareness and education
  • The importance of identifying a market niche before launch
  • Greater efficacy with fewer side-effects
  • A need for drugs targeting negative and cognitive symptoms, and partial-responders
  • Long-acting depots and patch technology are favored to improve patient compliance
• CHAPTER 3 R&D APPROACH
  • Classification of marketed and pipeline products
  • Serotonergic and dopaminergic receptor antipsychotics
  • Dopaminergic antipsychotics
  • Dopamine antagonists
  • Dopamine agonists
  • Serotonergic antipsychotics
  • Serotonin antagonists
  • Serotonin agonists
  • Novel antipsychotics
  • Alpha 2 adrenoceptor antagonists
  • Glutamate (AMPA and NMDA) and glycine receptor modulators
  • Cannabinoids
  • Cyclooxygenase-2 inhibitors
  • Monoaminergic antipsychotics
  • Muscarinic M(1) receptor agonists
  • Neurokinin 3 (NK3) receptor antagonists
  • Nicotinic acetylcholine receptor modulators
  • Secretin
  • Clinical trials and drug development
  • Clinical trial endpoints and schizophrenia rating scales
  • Positive and Negative Syndrome Scale
  • Brief Psychiatric Rating Scale
  • Brief Assessment of Cognition in Schizophrenia
  • Neuropsychological Assessment Battery
  • Other tests
  • A number of other tests are used in the diagnosis and monitoring of patients during general treatment management and for the duration of clinical trials:
  • Clinical trial design guidance
  • MATRICS recommendations for the clinical trial design for cognition enhancing drugs in schizophrenia
  • Key research recommendations
  • Increased focus on cost containment
  • Improved quality of life
• CHAPTER 4 PIPELINE DRUG ANALYSIS
  • Pipeline overview
  • Approved drugs yet to be launched
  • Drugs in pre-registration
  • Pipeline drugs in Phase III
  • Pipeline drugs in Phase II
  • Pipeline drugs in Phase I
  • Key companies involved in the development of novel schizophrenia therapeutics
  • J&J's schizophrenia franchise will decline from 2008 onwards despite the launch of paliperidone
  • Lundbeck's experience with marketing sertindole will provide a strong base from which to launch bifeprunox
  • Organon's asenapine will be an exciting entrant to the schizophrenia market
  • Pfizer's schizophrenia franchise will continue to grow through 2011
  • Dainippon-Sumitomo's blonanserin will first launch in Japan, despite competing with the recently launched Abilify
  • GSK's antipsychotic pipeline drugs are unlikely to have a significant impact on the schizophrenia market
  • Methodology of Datamonitor's competitive positioning analysis
  • Gold standard antipsychotic
  • The market value is calculated using IMS diagnosis value
  • Forecast caveats
• CHAPTER 5 LATE-STAGE PIPELINE DRUG ANALYSIS AND FORECASTS
  • Paliperidone
  • Clinical trial data
  • Study 1
  • Study 2
  • Study 3
  • Study 4
  • Study 5
  • Study 6
  • Completed trials
  • Ongoing clinical trials
  • Physicians not overly impressed with paliperidone therapeutic profile
  • Paliperidone IM - an improvement over Risperdal Consta?
  • Risperdal patent expiry and switch to paliperidone over generic risperidone
  • How will J&J price paliperidone IM compared to Risperdal Consta
  • Paliperidone ER will be the next entrant to the US market in H2 2006
  • Intramuscular Zyprexa
  • Clinical trial data
  • Ongoing clinical trials
  • Zyprexa's undesirable side-effect profile will limit the uptake of the long-acting IM formulation
  • Intramuscular Abilify
  • Clinical trial data
  • Study 1
  • Study 2
  • Study 3
  • Study 4
  • Study 5
  • Completed clinical trials
  • Abilify IM may lead to increased use of Abilify as a first-line maintenance therapy
  • Abilify needs to demonstrate strong efficacy in a head-to-head study
  • Multiple IM doses within a 24-hour period may limit use of Abilify IM compared to other IM formulations
  • How will Abilify IM be priced?
  • BMS/Otsuka should consider a long-acting IM version of Abilify
  • Sertindole
  • Clinical trial data
  • Study 1
  • Study 2
  • Study 3
  • Study 4
  • Study 5
  • Other clinical studies
  • Physicians not impressed with sertindole's tolerability despite new data
  • Sertindole will be the next entrant to the EU market in H2 2006
  • Asenapine (Org-5222)
  • Clinical trial data
  • Study 1
  • Study 2
  • Study 3
  • Study 4
  • Ongoing clinical trials
  • Asenapine's potential in treating negative symptoms will be a key therapeutic and commercial advantage
  • Twice daily dosing of asenapine may limit uptake
  • Asenapine will be the leading market entrant in terms of revenue value by 2015
  • Bifeprunox
  • Clinical trial data
  • Study 1
  • Additional clinical trial data
  • Completed clinical trials
  • Ongoing clinical trials
  • Bifeprunox's tolerability is a key therapeutic and commercial attribute
  • Bifeprunox unlikely to be used for acute psychosis, but may have a niche in first episode psychosis
  • Bifeprunox's pharmacokinetic profile is suitable for once-daily dosing, with a potential for numerous reformulation strategies
  • Solvay and Wyeth's experience in psychiatry and Lundbeck's launch of sertindole will provide a strong base for the commercialization of bifeprunox
  • Bifeprunox will be the second-highest new entrant in terms of cash value to the schizophrenia market by 2015
  • Blonanserin
  • Clinical trial data
  • Study 1
  • Study 2
  • Blonanserin demonstrates no clear advantages over marketed or pipeline schizophrenia drugs
  • Almirall's limited commercial presence in the EU, and lack of presence in the US will limit uptake of blonanserin outside of Japan
  • Blonanserin will receive its strongest uptake in the Japanese market
  • Seroquel SR
  • Clinical trial data
  • Ongoing clinical trials
  • Seroquel SR unlikely to provide significant differentiation from Seroquel
  • Seroquel will retain patent protection until 2011, safeguarding the initial uptake of Seroquel SR from generic quetiapine
  • Will US health insurers pay the increased costs for the SR formulation?
  • Seroquel SR is not expected to receive a strong uptake, and revenues will decline from 2012 onwards
  • Iloperidone
  • Clinical trial data
  • Ongoing clinical trials
  • If approved, QT will limit iloperidone uptake as a first-line therapy
  • Iloperidone offers no therapeutic advantage over marketed or pipeline schizophrenia drugs
  • Iloperidone will receive limited uptake in the US
• CHAPTER 6 PHASE II PIPELINE DRUG ANALYSIS
  • Introduction
  • ABT-089
  • Clinical trial data
  • Nicotinic agonists which improve cognitive functioning and smoking cessation would be valuable in the management of schizophrenia
  • ACP-103/ACP-104
  • ACP-103 clinical trial data
  • Study 1
  • Study 2
  • Study 3
  • Other trial data
  • Ongoing clinical trials
  • There is little need for an adjunct to improve positive symptoms, as marketed drugs already treat this domain of schizophrenia
  • ACP-104 clinical trial data
  • Study 1
  • Other trial data
  • Ongoing clinical trials
  • ACP-104 would be a significant treatment advance if it can demonstrate cognitive enhancement without the side effects of clozapine
  • AVE-1625
  • Dihydrexidine
  • Idazoxan
  • Clinical trial data
  • Study 1
  • Idazoxan is unlikely to be a standalone therapy, but may have a niche in treatment-resistant schizophrenia
  • Lurasidone
  • Clinical trial data
  • Completed clinical trials
  • Ongoing clinical trials
  • Lurasidone - another me-too atypical, and therefore of limited therapeutic and commercial potential
  • LY2140023
  • Ocaperidone
  • Clinical trial data
  • Study 1
  • Other clinical trial data
  • J&J may choose to relicense ocaperidone from Neuro3d if ocaperidone performs well in Phase II trials
  • Org-24448
  • Org-24448 may have potential in treating cognitive functioning
  • RG1068
  • Clinical trial data
  • Study 1
  • Other clinical trial data
  • Ongoing clinical trials
  • The subcutaneous formulation is unlikely be well received by patients
  • Sabcomeline
  • 773812 (SB-750093A)
  • Clinical trial data
  • Completed clinical trials
  • Ongoing clinical trials
  • SCA-136
  • Clinical trial data
  • Ongoing clinical trials
  • SGS518
  • Clinical trial data
  • Study 1
  • Study 2
  • Commercial and patient potential
  • Talnetant
  • Clinical trial data
  • Study 1
  • Other study data
  • Completed clinical trials
  • Ongoing clinical trials
  • Pharmacokinetic profile may hamper talnetant's clinical development
• CHAPTER 7 FUTURE TREATMENT OF SCHIZOPHRENIA
  • Future treatment of schizophrenia
• APPENDIX A
  • Forecast revenues
  • Competitive positioning analysis of pipeline schizophrenia drugs
  • Bibliography
  • Websites
  • Journal articles and conference abstracts
• APPENDIX B
  • Report methodology
  • Datamonitor forecast methodology
  • Sales calculations
  • About Datamonitor
  • About Datamonitor Healthcare
  • Datamonitor Healthcare's therapy area capabilities
  • List of Tables
    • Table 1: Diagnostic criteria for schizophrenia and its subtypes
    • Table 2: Prevalence of patients with schizophrenia exhibiting comorbid psychiatric disorders across the US, EU and Japan (%), 2005
    • Table 3: Risk factors for non-compliance to follow-up appointments and/or antipsychotics in patients with schizophrenia
    • Table 4: Potential strategies for improving compliance in patients with schizophrenia
    • Table 5: Novel antipsychotic drug classes in development for the treatment of schizophrenia,2006
    • Table 6: Approved drugs yet to be launched in the US, EU and Japan for the treatment of psychosis and schizophrenia, 2006
    • Table 7: Pipeline drugs in pre-registration for the treatment of psychosis and schizophrenia, 2006
    • Table 8: Pipeline drugs in Phase III development for psychosis and schizophrenia, 2006
    • Table 9: Pipeline drugs in Phase II development for psychosis and schizophrenia, 2006
    • Table 10: Pipeline drugs in Phase I development for psychosis and schizophrenia, 2006
    • Table 11: J&J's pipeline schizophrenia drugs, 2006
    • Table 12: Lundbeck's pipeline schizophrenia drugs, 2006
    • Table 13: Organon's pipeline schizophrenia drugs, 2006
    • Table 14: Pfizer's pipeline schizophrenia drugs, 2006
    • Table 15: Dainippon-Sumitomo's pipeline schizophrenia drugs, 2006
    • Table 16: GSK's pipeline schizophrenia drugs, 2006
    • Table 17: Commercial strength/weakness factors - weightings and scoring definitions
    • Table 18: Product-specific strength/weakness factors - weightings and scoring definitions
    • Table 19: Proportion of total molecule volume (SU and sales) of antipsychotics, accounted for by schizophrenia diagnoses in the US, EU and Japan, 2005
    • Table 20: Comparison of paliperidone IM versus Risperdal Consta
    • Table 21: Price of different formulations of Risperdal ($), 2001-05
    • Table 22: Revenues of the rapid-acting atypical antipsychotic IMs ($m), 2002-05
    • Table 23: Price points for the rapid-acting atypical antipsychotic IMs ($), 2004-06
    • Table 24: Asenapine can address most of the unmet needs for the treatment of schizophrenia
    • Table 25: Datamonitor's forecast schizophrenia revenues of marketed and pipeline schizophrenia drugs across the US, EU and Japan ($m), 2006-2015
    • Table 26: Datamonitor's competitive positioning analysis of pipeline schizophrenia drugs according to product-specific strength/weakness factors, 2006
    • Table 27: Datamonitor's competitive positioning analysis of pipeline schizophrenia drugs according to commercial strength/weakness factors, 2006
    • Table 28: Schizophrenia market definition by ICD10 code
  • List of Figures
    • Figure 1: Forecast schizophrenia revenues of marketed and pipeline schizophrenia drugs across the US, EU and Japan, 2006-2015
    • Figure 2: Datamonitor's competitive positioning analysis of pipeline schizophrenia drugs compared to marketed comparators, 2006
    • Figure 3: Reasons for non-compliance among schizophrenia patients receiving antipsychotic therapy
    • Figure 4: Drug classes in development for the treatment of schizophrenia, 2006
    • Figure 5: NICE measurement of cost-effectiveness of drug treatment
    • Figure 6: Forecast revenues for J&J's schizophrenia franchise (Risperdal and paliperidone), 2006-2015
    • Figure 7: Datamonitor's competitive positioning analysis of J&J's marketed and pipeline schizophrenia drugs, 2006
    • Figure 8: Datamonitor's competitive positioning analysis of Lundbeck's pipeline schizophrenia drugs, 2006
    • Figure 9: Forecast revenues of Lundbeck's schizophrenia franchise(Serdolect and bifeprunox (Lundbeck's share - EU only), 2006-2015
    • Figure 10: Datamonitor's competitive positioning analysis of Pfizer's marketed and pipeline schizophrenia drugs, 2006
    • Figure 11: Forecast revenues of Organon's schizophrenia franchise (asenapine), 2006-2015
    • Figure 12: Datamonitor's competitive positioning analysis of Pfizer's marketed and pipeline schizophrenia drugs, 2006
    • Figure 13: Forecast revenues of Pfizer's schizophrenia franchise (Geodon and asenapine), 2006-2015
    • Figure 14: Paliperidone ER only meets one of the criteria for a therapeutically and commercially successful drug reformulation
    • Figure 15: Datamonitor's competitive positioning analysis of paliperidone ER and IM, 2006
    • Figure 16: Datamonitor's forecast of paliperidone's revenues across the US, EU and Japan ($m), 2006-2015
    • Figure 17: Zyprexa's declining US revenues, and plateauing EU revenues
    • Figure 18: Datamonitor's competitive positioning analysis of Zyprexa IM, 2006
    • Figure 19: Datamonitor's competitive positioning analysis of Abilify IM, 2006
    • Figure 20: Datamonitor's competitive positioning analysis of sertindole, 2006
    • Figure 21: Datamonitor's forecast of sertindole's revenues across the five major EU markets ($m), 2006-2015
    • Figure 22: Datamonitor's competitive positioning analysis of asenapine, 2006
    • Figure 23: Datamonitor's forecast of asenapine's revenues across the US, EU and Japan ($m), 2006-2015
    • Figure 24: Datamonitor's competitive positioning analysis of bifeprunox, 2006
    • Figure 25: Datamonitor's forecast of bifeprunox's revenues across the US, EU and Japan ($m), 2006-2015
    • Figure 26: Datamonitor's competitive positioning analysis of blonanserin, 2006
    • Figure 27: Datamonitor's forecast of blonanserin's revenues across the US, EU and Japan, 2006-2015
    • Figure 28: Seroquel SR meets two out of three criteria for a therapeutically and commercially successful drug reformulation
    • Figure 29: Datamonitor's competitive positioning analysis of Seroquel SR, 2006
    • Figure 30: Datamonitor's forecast of Seroquel SR's revenues across the US, EU and Japan, 2006-2015
    • Figure 31: Datamonitor's competitive positioning analysis of iloperidone, 2006
    • Figure 32: Datamonitor's forecast of iloperidone's revenues across the US, EU and Japan, 2006-2015
    • Figure 33: Polypharmacology affinity of atypical antipsychotics for serotonergic, dopaminergic, adrenergic, muscarinic and histaminergic receptors