抗血栓剤：予防薬市場への参入

Introduction

Novel oral anticoagulants and antiplatelet agents will have a profound impact on the antithrombotics market. expects Bayer rivaroxaban and Sankyo/Eli Lilly prasugrel to achieve blockbuster status. Parenteral anticoagulants are not expected to be large revenue generators, due to low clinical unmet need in this market segment and strong competition from current gold standard agents.

Scope

• Event-driven sales projections for 2007-16 for key late-stage developmental antithrombotics in the seven major markets
• Commercial analysis of late-stage developmental compounds in terms of their ability to satisfy unmet clinical needs
• An overview of the antithrombotics R&D pipeline with a comprehensive assessment of all classes in development
• Analysis of the potential for developmental antithrombotics with respect to the patient populations for which they are indicated

Report Highlights

Following the abrupt withdrawal of AstraZeneca Exanta in February 2006, Bayer Healthcare rivaroxaban and Boehringer Ingelheim Rendix are well positioned to profit from patients switching from warfarin, and market growth obtained by recruiting the previously untreated population.

The highest selling brands in the antidiabetics market are Lovenox (enoxaparin) and Plavix (clopidogrel), but these agents will be genericized within our forecast period. Consequently, pipeline agents are expected to become significant drivers in the market.

Acute Coronary Syndrome is usually the first indication for which novel anticoagulants are approved; this is a quick route to market, while drug companies then prepare to launch their products in more lucrative, chronic treatment markets.

Reasons to Purchase

• Understand the factors that will drive the success of next-generation antithrombotics
• Overcome the barriers to entry generated by lifecycle strategies of key players in the market
• Assess the remaining market opportunity, where established therapies and other developmental compounds fail to address key unmet clinical needs

Table of Contents

• About the Disease pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of the analysis
  • Key metrics
    • Anticoagulants
    • Antiplatelet Agents
• CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS
  • Pipeline overview
  • Antithrombotics segmented by mechanism of action
    • Redesigning heparin: the race for ideal coagulation cascade target is still open
    • Antiplatelet agents by drug class
  • Antithrombotics segmented by developing company
    • Japanese companies in the antithrombotics market
  • Key companies involved in the antithrombotics pipeline
    • Overview
    • AstraZeneca
    • Sanofi-Aventis
• CHAPTER 3 PATIENT POTENTIAL
  • Definition of antithrombotic market
  • Antithrombotic launch indications
    • Venous thrombosis
      • VTE prophylaxis in patients undergoing major orthopedic surgery
      • Treatment and secondary prevention of acute venous thromboembolism
    • Arterial thrombosis
      • Coronary thrombosis
      • Acute coronary syndromes
      • Incidence of STEMI
      • Incidence of UA and NSTEMI
    • Cerebrovascular thrombosis
      • Stroke treatment
      • Stroke prevention in atrial fibrillation patients (SPAF)
    • Peripheral thrombosis
      • Peripheral arterial disease (PAD)
  • Marketing considerations: unmet needs, barriers to market entry and uptake
    • Anticoagulants
      • Unmet needs: parenteral anticoagulants
      • Unmet needs: oral anticoagulants
      • Unmet need: increased physician awareness of VTE
      • Points of consideration: factors influencing market entry and uptake
      • Unmet needs summary
    • Antiplatelets
      • Unmet needs
      • Unmet need for rapid onset of action in interventional cardiology
      • Unmet need: increased physician awareness for the need of therapy for PAD
      • Points of consideration: factors influencing market entry and uptake
      • Unmet needs summary
• CHAPTER 4 R&D APPROACH
  • Classification of pipeline products
    • Anticoagulants
      • Hemostasis and the coagulation cascade
      • Indirect thrombin inhibitors
      • Unfractionated heparin (UFH)
      • Low molecular weight heparin (LMWH)
      • Direct thrombin inhibitors (DTIs)
      • Factor IXa inhibitors
      • Factor Xa inhibitors
      • Factor VIIa inhibitors/tissue factor pathway inhibitors
      • Anticoagulant activity
    • Antiplatelet Agents
      • Cyclo-oxygenase (COX) inhibitors: aspirin
      • ADP antagonists
      • GPIIb/IIIa inhibitors
      • PGE-1 antagonists
      • PI3-kinase antagonists
      • PGH2/TXA2 (TP) receptor antagonists
  • Clinical trial design for antithrombotics
    • Phase III sample size
    • Choice of control drug
    • Patient exclusion
    • Patient exclusion from efficacy analysis
    • Duration of drug intervention
    • Pre-operative or post-operative initiation of prophylaxis?
    • Dosing interval
    • Dose timing
  • Clinical trial endpoints for antithrombotics
    • Efficacy endpoints
      • VTE incidence
      • Diagnosis of VTE events
      • Central versus local adjudication
    • Safety endpoints
• CHAPTER 5 ANTICOAGULANTS LATE-STAGE DRUG ANALYSIS AND FORECASTS
  • Overview of the key anticoagulants in late-stage development
    • Pipeline summary
    • drug assessment summary
    • Comparative forecasts
  • Rivaroxaban (BAY-59-7939)
    • Drug overview
    • Clinical data
    • Patient potential
    • Marketing factors
    • Forecasts to 2016
  • Dabigatran etexilate (BIBR-1048) - Rendix
    • Drug overview
    • Clinical data
      • Pharmacokinetics of dabigatran etexilate
      • Phase II clinical trial of Dabigatran etexilate in MOS versus enoxaparin: BISTRO II
    • Patient potential
      • SPAF - greatest potential for dabigatran etexilate
      • Potential device competitor for SPAF indication for high-risk patients?
    • Marketing factors
    • Forecast to 2016
  • Idraparinux
    • Drug overview
    • Clinical data
      • PERSIST trial
      • No significant effect on liver enzymes
      • Phase III VAN GOGH trial in PE patients
      • Phase III AMADEUS trial
    • Patient potential
    • Marketing factors
      • Strong presence and experience in the AF market
      • High price may pose a barrier to uptake
      • Lack of antidote raises concerns
    • Forecast to 2016
  • ART-123
    • Drug overview
    • Clinical data
      • Phase III trials
      • Phase I trials
      • Prevention of VTE after total hip replacement
    • Patient potential
    • Marketing factors
    • Forecast to 2016
• CHAPTER 6 OTHER ANTICOAGULANTS
  • Antithrombin aptamers - NU-172 and ARC1779
    • Drug overview
    • Preclinical data
    • Clinical data
  • Apixaban (BMS-562247)
    • Drug overview
    • Clinical data
  • AVE-5026
    • Drug overview
    • Clinical data
  • AZD-0837
    • Drug overview
    • Clinical data
  • AZD-9684
    • Drug overview
    • Preclinical data
  • Biotinylated Idraparinux (SSR-126517)
    • Drug overview
    • Clinical data
  • DU-176b
    • Drug overview
    • Clinical data
  • E-5555
    • Drug overview
    • Preclinical data
    • Clinical data
  • Elaprin (Oral heparin) and Oral LMWH
    • Drug overview
    • Clinical data
    • comment
  • Flovagatran (TGN-255)
    • Drug overview
    • Clinical data
    • comments
  • GSK-813893
    • Drug overview
  • LY-517717
    • Drug overview
    • Clinical data
  • Odiparcil (SB-424323)
    • Drug overview
    • Clinical data
  • Otamixaban (XRP-0673)
    • Drug overview
    • Clinical data
  • PD-348292
    • Drug overview
  • Pegmusirudin (SPP-200; LU-57291)
    • Drug overview
    • Clinical data
  • PRT-54021
    • Drug overview
    • Clinical data
  • REG-1
    • Drug overview
    • Clinical data
  • SCH-530348
    • Drug overview
    • Preclinical data
    • Clinical data
  • Sofigatran (MCC-977)
    • Drug overview
  • SR-123781
    • Drug overview
    • Preclinical data
    • Clinical data
  • Tanogitran (BIBT-986)
    • Drug overview
    • Clinical data
  • TGN-167
    • Drug overview
    • Clinical data
  • TTP-889
    • Drug overview
    • Clinical data
    • comment
  • YM-150
    • Drug overview
    • Clinical data
• CHAPTER 7 ANTIPLATELET AGENTS: LATE-STAGE ANALYSIS AND FORECASTS
  • Overview of the key antiplatelets in late-stage development
    • Pipeline summary
    • drug assessment summary
    • Comparative forecasts
  • Prasugrel (CS-747)
    • Drug overview
    • Clinical data
      • Phase IIa: Randomized two-way cross-over, open-label study in healthy subjects
      • Phase IIa : Randomized, partially blind, parallel group dose-ranging study
    • Patient potential
    • Marketing factors
    • Forecast to 2016
  • Cangrelor (AR-C69931)
    • Drug overview
    • Clinical Data
    • Patient potential
    • Marketing factors
    • Forecast to 2016
  • Ticagrelor (AZD-6140)
    • Drug overview
    • Clinical data
    • Patient Potential
    • Marketing Factors
    • Forecast to 2016
• CHAPTER 8 OTHER ANTIPLATELET AGENTS
  • DA-697b
    • Drug overview
    • Preclinical data
  • DG-041
    • Drug overview
    • Preclinical data
    • Clinical data
  • Ecraprost
    • Drug overview
    • Clinical data
    • comment
  • Liprostin
    • Drug overview
    • Clinical data
  • Parogrelil (NM-702)
    • Drug overview
    • Clinical data
  • PR-15
    • Drug overview
    • Preclinical data
    • Clinical data
    • comment
  • S-18886
    • Drug overview
    • Clinical data
  • SL-650472
    • Drug overview
    • Preclinical data
    • Clinical data
• BIBLIOGRAPHY
  • Epidemiology
    • National hospital discharge data
• APPENDIX A
  • Methodology
    • forecast methodology
      • Product forecasts
      • Estimated 2006 sales revenue
      • Definition of a standard unit (only use if ForeSight model used to forecast)
    • drug assessment summary
  • Contributing experts
• APPENDIX B
  • About
    • About Healthcare
  • Healthcare therapy area capabilities
    • About the Disease analysis team
    • Key therapy team members
    • Disclaimer
  • List of Tables
    • Table 1: Forecast key pipeline products in Antithrombotics in 2016 ($m)
    • Table 2: Anticoagulant agents in the R&D pipeline, 2007
    • Table 3: Antiplatelet agents in the R&D pipeline, 2007.
    • Table 4: Key players in antithrombotic drug development, 2007
    • Table 5: Incidence of arthroplastic knee surgery in the seven major markets (000s), 2007-2017
    • Table 6: Incidence of arthroplastic hip surgery in the seven major markets (000s), 2007-2017)
    • Table 7: Incidence of deep vein thrombosis, pulmonary embolism and venous thromboembolism in the seven major markets(000s), 2007-2017
    • Table 8: Incidence of ST-segment elevation myocardial infarction (000s), 2007-2017
    • Table 9: Incidence of unstable angina and non-ST segment elevation myocardial infarction in the seven major markets (000s), 2007-2017
    • Table 10: Incidence of percutaneous coronary intervention in the seven major markets (000s), 2007-2017
    • Table 11: Incidence of stroke in the seven major markets (000s), 2007-2017
    • Table 12: Proportion of atrial fibrillation patients at risk of developing stroke
    • Table 13: Prevalence of chronic atrial fibrillation in the seven major markets (000s), 2007-2017
    • Table 14: Prevalence of peripheral arterial disease in the seven major markets (000s), 2007-2017
    • Table 15: Resistance to key oral antiplatelets
    • Table 16: Advantages of direct thrombin inhibitors over heparin
    • Table 17: OASIS-5/Michelangelo trial: efficacy
    • Table 18: OASIS-5/Michelangelo trial: safety
    • Table 19: Key results of CURE substudy
    • Table 20: CLARITY/TIMI-28: efficacy outcomes on angiography
    • Table 21: CLARITY/TIMI-28: safety outcomes
    • Table 22: COMMIT/CCS-2 trial: efficacy endpoints
    • Table 23: COMMIT/CCS-2 trial: safety endpoints
    • Table 24: COMMIT/CCS-2 trial: time to treatment
    • Table 25: COMMIT/CCS-2 trial: thrombolytic background therapy
    • Table 26: ARMYDA-2: number of events at 30 days
    • Table 27: ARMYDA-2: postprocedural peak biomarker levels
    • Table 28: ARMYDA-2: percentage of patients with an elevation of CKMB/troponin I
    • Table 29: ARMYDA-2: number of bleeding events at 30 days
    • Table 30: Key efficacy endpoints used in anticoagulant clinical trials
    • Table 31: Key safety endpoints used in anticoagulant clinical trials
    • Table 32: Key anticoagulants in late-stage development, 2007
    • Table 33: Sales forecasts for late-stage anticoagulants in the seven major markets ($m), 2007-2016
    • Table 34: Proportion of AF patients receiving antithrombotic therapy by level of risk of experiencing stroke
    • Table 35: Comparison of fondaparinux with idraparinux
    • Table 36: PERSIST trial results
    • Table 37: Result of dose-response trial examining ART-123
    • Table 38: Key pipeline antiplatelets, 2007
    • Table 39: Comparative Sales Forecast for late-stage antiplatelet agents
    • Table 40: JUMBO-TIMI 26: number of adverse events
    • Table 41: JUMBO-TIMI 26: patient characteristics
    • Table 42: JUMBO-TIMI 26: primary endpoint (significant bleeding)
    • Table 43: JUMBO-TIMI 26: TIMI major bleeding
    • Table 44: JUMBO-TIMI 26: total bleeding episodes (TIMI major/minor and minimal)
    • Table 45: JUMBO-TIMI 26: secondary endpoint (MACE)
    • Table 46: JUMBO-TIMI 26: MACE components
    • Table 47: drug assessment parameters
  • List of Figures
    • Figure 1: drug assessment summary of pipeline anticoagulants, , 2007-2016
    • Figure 2: drug assessment summary of pipeline antiplatelets, 2007-2016
    • Figure 3: The antithrombotics pipeline by development stage, 2007
    • Figure 4: Antithrombotics development pipeline segmented by mechanism of action, 2007
    • Figure 5: Pipeline antithrombotics segmented by developing company, 2007
    • Figure 6: Key players in the antithrombotics pipeline with products segmented by phase of development, 2007
    • Figure 7: Overlap of ischemic cardiovascular conditions
    • Figure 8: Frequency of disease with symptoms in the three organ systems and their overlap, from the CAPRIE trial
    • Figure 9: Risk of stroke increases with age
    • Figure 10: Breakdown of the peripheral arterial disease population by classification
    • Figure 11: The targets of developmental anticoagulants and selected thrombolytics
    • Figure 12: Aspirin inhibits platelet COX-1 irreversibly
    • Figure 13: The role of purinergic receptors as targets for antiplatelets
    • Figure 14: GPIIb/IIIa receptor antagonists act directly on the receptor
    • Figure 15: CLARITY/TIMI-28: study design
    • Figure 16: COMMIT/CCS-2 trial: dual antiplatelet therapy in acute myocardial infarction
    • Figure 17: ARMYDA-2: trial design
    • Figure 18: drug assessment summary of pipeline anticoagulants, 2007-2016
    • Figure 19: Comparative sales forecast for late-stage anticoagulants in the seven major markets, 2007-2016
    • Figure 20: projected sales for rivaroxaban (BAY-59-7939) in across the seven major markets ($m), 2007-2016
    • Figure 21: projected sales for Rendix (dabigatran etexilate, BIBR-1048) in across the seven major markets ($m), 2007-2016.
    • Figure 22: PERSIST trial design
    • Figure 23: Idraparinux Phase III program: VAN GOGH
    • Figure 24: Idraparinux Phase III program: AMADEUS
    • Figure 25: Is recombinant factor VIIa a valid antidote to idraparinux?
    • Figure 26: projected sales for idraparinux in across the seven major markets ($m), 2007-2016
    • Figure 27: projected sales for ART-123 in across the seven major markets ($m), 2007-2016
    • Figure 28: drug assessment summary of pipeline antiplatelet agents, 2007-2016
    • Figure 29: Comparative sales forecast for late-stage antiplatelet agents
    • Figure 30: JUMBO-TIMI 26: prasugrel in the setting of percutaneous coronary intervention
    • Figure 31: TRITON-TIMI-38: trial design
    • Figure 32: projected sales for prasugrel in across the seven major markets ($m), 2007-2016
    • Figure 33: projected sales for cangrelor in across the seven major markets ($m), 2007-2016
    • Figure 34: Ticagrelor (AZD-6140) is a potent inhibitor of platelet aggregation
    • Figure 35: projected sales for ticagrelor in across the seven major markets ($m), 2007-2016
    • Figure 36: drug assessment summary of pipeline molecular targeted therapies in development for hematological malignancies, 2007