Pipeline Insight: Acute Stroke: Commercial Risk Offsets High Unmet Need

Content

• about Datamonitor Healthcare
  • about the cardiovascular pharmaceutical analysis team
• Chapter 1 Executive Summary
  • Scope of the analysis
  • Experts interviewed for this report (interviewed in April 2008)
  • Experts interviewed for Pipeline Insight 2006: Acute Stroke, DMHC2167 (interviewed in February 2006)
  • Experts interviewed for Stakeholder Insight 2007: Acute Stroke, DMHC2286 (interviewed in October 2007)
  • Datamonitor insight into the acute stroke market
  • The R&D pipeline for acute stroke is a diverse and bisegmental collection of 34 novel agents at the clinical stages of drug development
  • The R&D landscape in the setting of acute stroke is not dominated by any one company. IT is shaped by the need to minimize the commercial risk associated with developing drugs for the acute-care stroke market
  • The acute stroke market is characterized by high unmet market need as well as high unmet clinical need
  • The numerous failures of agents in development for acute stroke management result mainly from clinical trial design issues
  • Datamonitor has identified four candidate drugs that have potential to be launched into the acute stroke market within the near future - the vasoprotectant clazosentan, the thrombolytics desmoteplase and tenecteplase and the defibrinogenating agent Viprinex (ancrod)
• Chapter 2 Pipeline Overview and Dynamics
  • Pipeline overview
  • Acute stroke: a diversified pipeline
  • Acute stroke: a balanced pipeline
  • The R&D landscape is not dominated by any one company
• Chapter 3 Patient Potential
  • Disease definition and segmentation
  • Symptoms
  • Epidemiology and patient potential
  • Epidemiology methodology
  • US
  • Japan
  • Europe
  • Incidence of pre-hospital mortality in stroke
  • Types of stroke: relative frequency of ischemic stroke over hemorrhagic stroke
  • Ischemic stroke
  • Patient potential: incidence of patients presenting with ischemic stroke
  • Hemorrhagic stroke
  • Intracerebral hemorrhage
  • Subarachnoid hemorrhage
  • Patient potential: incidence of patients presenting with hemorrhagic stroke
  • Transient ischemic attack
  • Marketability considerations: barriers to market entry and uptake
  • Points of consideration: factors influencing market entry and uptake
  • Unmet market needs
  • Physician education: tackling physician competence and attitude
  • Patient education: raising stroke-symptom awareness
  • Infrastructural unmet needs: establishing, maintaining and expanding the network of dedicated stroke units
  • Unmet clinical needs
  • Procoagulation
  • Neuroprotection
  • Revascularization
• Chapter 4 R&d Approach
  • Classification of pipeline products
  • Acute stroke pipeline
  • Mechanisms affecting the status of hemostasis
  • Hemostasis and the coagulation cascade
  • Coagulation factors (procoagulants)
  • Thrombolytics
  • The current comparator therapy: alteplase
  • Mechanisms affecting the status of neuronal tissue
  • Neurotrophic drugs
  • Glutamate antagonists
  • GABA agonists
  • Ion channel modulators
  • Free radical scavengers
  • Other mechanisms
  • The current comparator therapies: citicoline and edavarone
  • Mechanisms affecting the status of vasospasm
  • ET-A antagonists
  • The current comparator therapy: nimodipine
  • Clinical trial design
  • Patient population should be assessed for severity and potential responders
  • The concept of the ischemic penumbra: the potential of diagnosing salvageable tissue
  • Safety endpoints
  • Efficacy endpoints
  • Critique of previous failures
  • Currently available neuroprotectants - failure to make an impact?
  • Neuroprotectants - brief history of development
  • Recent failures
  • Neuroprotectants - potential reasons for failure
  • Possible answers for future clinical trials
• Chapter 5 Late-Stage Drug Analysis & Forecasts: Vasoprotective Therapies
  • Overview of Vasoprotective Therapies in Late-Stage Development for Acute Stroke
    • Pipeline summary
    • Comparator therapy
    • Nimodipine
    • Clazosentan
    • Drug overview
    • Preclinical data
    • Clinical data
    • Phase I
    • Phase II
    • Phase II/III - CONSCIOUS-I
    • Phase III - CONSCIOUS-II
    • Patient potential
    • Marketing factors
    • Satisfaction of unmet needs
    • Forecast to 2017
    • Datamonitor comments
    • Datamonitor drug assessment summary
• Chapter 6 Late-Stage Drug Analysis & Forecasts: Reperfusion Therapies
  • Overview of Reperfusion Therapies in Late-Stage Development for Acute Stroke
    • Pipeline summary
    • Comparator therapy
    • Desmoteplase
    • Drug overview
    • Preclinical data
    • Pharmacokinetics
    • Toxicity
    • Neuroprotection
    • Clinical data
    • Phase II: DIAS
    • Phase II: DEDAS
    • Phase III: DIAS-2
    • Phase III: new trial
    • Patient potential
    • Marketing factors
    • Satisfaction of unmet needs
    • Forecast to 2017
    • Datamonitor comments
    • Datamonitor drug assessment summary
    • Viprinex (ancrod)
    • Drug overview
    • Clinical data
    • Phase II clinical trials
    • Phase III clinical trials
    • Patient potential
    • Marketing factors
    • Satisfaction of unmet needs
    • Forecast to 2017
    • Datamonitor comments
    • Datamonitor drug assessment summary
    • Tenecteplase
    • Drug overview
    • Clinical data
    • Phase I clinical trials
    • Phase II clinical trials
    • Patient potential
    • Marketing factors
    • Satisfaction of unmet needs
    • Forecast to 2017
    • Datamonitor comments
    • Datamonitor drug assessment summary
• Chapter 7 Other Acute Stroke Drugs
  • AEOL-10150
  • Drug overview
  • Preclinical data
  • Clinical data
  • AGY-94806 (SA-4503, Msc-1)
  • Drug overview
  • Preclinical data
  • AL-208
  • Drug overview
  • Preclinical data
  • Clinical data
  • Phase I
  • AX-200
  • Drug overview
  • Preclinical data
  • Clinical data
  • Caffeinol
  • Drug overview
  • Preclinical data
  • Clinical data
  • Candesartan
  • Drug overview
  • Clinical data
  • Phase III - ACCESS
  • Phase III - SCAST
  • CellBead Neuro
  • Drug overview
  • DP-b99
  • Drug overview
  • Preclinical data
  • Clinical data
  • Phase I
  • Phase II
  • Enecadin
  • Drug overview
  • Preclinical development
  • HTU-PA
  • Drug overview
  • Preclinical data
  • Clinical data
  • Phase I
  • KN-38-7271
  • Drug overview
  • Preclinical data
  • MC-1
  • Drug overview
  • Preclinical data
  • Clinical data
  • Phase I
  • Phase II
  • MC-1 (IV)
  • Drug overview
  • Microplasmin
  • Drug overview
  • Preclinical data
  • Clinical data
  • Phase I
  • Phase II
  • Neu-2000
  • Drug overview
  • Preclinical data
  • Clinical data
  • Phase I
  • NH-02D
  • Drug overview
  • NTx-265
  • Drug overview
  • Preclinical data
  • Clinical data
  • Phase I
  • Phase II
  • ONO-2506 (proglia, Arocyte)
  • Drug overview
  • Preclinical data
  • Clinical data
  • ONO-2231
  • Drug overview
  • Preclinical data
  • PGX-100
  • Drug overview
  • Preclinical data
  • RVX-208
  • Drug overview
  • Preclinical data
  • Clinical data
  • Phase I
  • S-0139
  • Drug overview
  • Solulin
  • Drug overview
  • Preclinical data
  • Clinical data
  • Phase I
  • SonoLysis+tPA
  • Drug overview
  • S-18986
  • Drug overview
  • Preclinical data
  • SUN-N4057
  • Drug overview
  • Preclinical data
  • Clinical data
  • SUN-N8075
  • Drug overview
  • Preclinical data
  • Clinical data
  • TAT-NR2B9c
  • Drug overview
  • Preclinical data
  • Tissue protective cytokines, Warren/Lundbeck/Shire
  • Drug overview
  • Preclinical data
  • V10153
  • Drug overview
  • Preclinical data
  • Clinical data
• Appendix A
  • Bibliography
  • Epidemiology
  • Other
  • Forecasting methodology
  • Datamonitor drug assessment methodology
  • Report methodology
• Appendix B
  • about Datamonitor
  • about Datamonitor Healthcare
  • Datamonitor Healthcare's therapy area capabilities
  • about the cardiovascular analysis team
  • Disclaimer
• List of Tables
  • Table 1: Products in clinical development for acute stroke, 2008
  • Table 2: Acute stroke pipeline (agents acting on CNS), 2008
  • Table 3: Acute stroke pipeline (agents acting on hemostasis), 2008
  • Table 4: Acute stroke pipeline by mechanism of action, 2008
  • Table 5: Acute stroke pipeline by company, 2008
  • Table 6: Estimated incidence of acute stroke across the seven major markets, 2008-2017
  • Table 7: Overall stroke patients: annual pre-hospital mortality, 2007
  • Table 8: Overall stroke patients: future estimated incidence of pre-hospital mortality in the seven major markets, 2008-2017 (000s)
  • Table 9: Proportion of stroke patients with ischemic stroke versus hemorrhagic stroke, 2007
  • Table 10: Estimated incidence of patients presenting with ischemic stroke in the seven major markets, 2008-2017 (000s)
  • Table 11: Estimated incidence of patients presenting with hemorrhagic stroke in the seven major markets, 2008-2017 (000s)
  • Table 12: Standardized outcome scales frequently used in clinical trials for acute stroke
  • Table 13: Key pipeline vasoprotective therapies in late-stage development for acute stroke, 2008
  • Table 14: Ability of clazosentan to satisfy the unmet needs, 2008
  • Table 15: Clazosentan sales forecast for acute stroke across the seven major markets, 2011-2017
  • Table 16: Key pipeline reperfusion therapies late-stage development for acute stroke, 2008
  • Table 17: DEDAS: safety endpoints
  • Table 18: Ability of desmoteplase to satisfy the unmet needs, 2008
  • Table 19: Desmoteplase sales forecast for acute stroke across the seven major markets, 2012-2017
  • Table 20: Percentage of stroke patients presenting to hospital within 6 hours (cumulative), 2007
  • Table 21: Ability of ancrod to satisfy the unmet needs, 2008
  • Table 22: Viprinex sales forecast for acute stroke across the seven major markets, 2011-2017
  • Table 23: Comparison of alteplase and tenecteplase
  • Table 24: Ability of tenecteplase to satisfy the unmet needs, 2008
  • Table 25: Tenecteplase sales forecast for acute stroke across the seven major markets, 2012-2017
  • Table 26: Datamonitor drug assessment parameters
• List of Figures
  • Figure 1: Acute stroke pipeline, 2008
  • Figure 2: Pipeline maturity: percentage of R&D products in each phase of development, 2008
  • Figure 3: Acute stroke pipeline maturity: percentage of R&D products in each phase of development by class, 2008
  • Figure 4: Acute stroke pipeline maturity: percentage of R&D products in each phase of development by type of company, 2008
  • Figure 5: The targets of developmental antithrombotics in the setting of acute stroke
  • Figure 6: Urokinase mechanism of action
  • Figure 7: Ancrod acts indirectly on the thrombolytic pathways
  • Figure 8: ECASS-III trial: extending the treatment window of tPA
  • Figure 9: Trial design of EPITHET
  • Figure 10: The ischemic cascade
  • Figure 11: Clazosentan sales forecast for acute stroke across the seven major markets, 2010-2017
  • Figure 12: Datamonitor drug assessment summary for clazosentan and nimodipine in acute stroke
  • Figure 13: Desmoteplase sales forecast for acute stroke across the seven major markets, 2012-2017
  • Figure 14: Datamonitor drug assessment summary of thrombolytic agents (desmoteplase according to the current data)
  • Figure 15: Datamonitor drug assessment summary of thrombolytic agents (desmoteplase according to Phase II data)
  • Figure 16: Viprinex sales forecast for acute stroke across the seven major markets, 2012-2017
  • Figure 17: Datamonitor drug assessment summary of thrombolytic agents (desmoteplase according to Phase II data)
  • Figure 18: Tenecteplase sales forecast for acute stroke across the seven major markets, 2012-2017
  • Figure 19: Datamonitor drug assessment summary of tenecteplase
  • Figure 20: Multimodal efficacy of AX-200
  • Figure 21: Datamonitor drug assessment summary of pipeline molecular targeted therapies in development for hematological malignancies, 2007