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Published by: Datamonitor
Published: Oct. 4, 2005 - 383 Pages
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE
- About the cardiovascular pharmaceutical analysis team
- CHAPTER 1 EXECUTIVE SUMMARY
- Scope of the analysis
- Datamonitor insight into the antithrombotics market
- The R&D pipeline for antithrombotics is a Phase II-heavy cornucopia of novel agents
- Of the three antithrombotic classes only the anticoagulant class and the antiplatelet class comprise drugs with blockbuster potential
- There is little commercial potential for novel parenteral anticoagulants and for thrombolytics
- Lifecycle management of established brands erects market entry barriers for novel agents
- CHAPTER 2 PIPELINE DYNAMICS
- Pipeline overview
- Antithrombotics segmented by class
- Anticoagulants by drug class
- Antiplatelets by drug class
- Thrombolytics by drug class
- Antithrombotics segmented by company
- Key companies involved in the antithrombotics pipeline
- Overview
- 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
- Cerebrovascular thrombosis
- Stroke treatment
- Stroke prevention in atrial fibrillation patients (SPAF)
- Peripheral thrombosis
- Peripheral arterial disease (PAD)
- Marketability 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
- Thrombolytics
- Unmet needs
- Points of consideration: thrombolytic Indications
- 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
- Enhancing natural anticoagulant activity
- The current comparator therapy
- Antiplatelets
- Cyclo-oxygenase (COX) inhibitors: aspirin
- ADP antagonists
- GPIIb/IIIa inhibitors
- PGE-1 antagonists
- PI3-kinase antagonists
- PGH2/TXA2 (TP) receptor antagonists
- The current comparator therapy: Plavix (clopidogrel)
- Thrombolytics
- Plasminogen activators
- Inhibitors of plasminogen activator inhibitor-1
- Direct clot lytics
- The current comparator therapies: alteplase and tenecteplase
- Comparison of marketed tPA-based thrombolytics
- 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
- Angiographic endpoints (TIMI flow grades)
- Central versus local adjudication
- Safety endpoints
- Bleeding
- CHAPTER 5 ANTICOAGULANTS LATE-STAGE DRUG ANALYSIS AND FORECASTS
- Overview of the key anticoagulants to be launched in long-term indications
- Pipeline summary
- Datamonitor drug assessment summary
- BAY-597939
- Drug overview
- Preclinical data
- Clinical data
- Patient potential
- Marketing factors
- BAY-597939: performance against benchmark criteria
- SWOT analysis: BAY-597939
- Forecast to 2015
- Datamonitor comments
- BIBR-1048 (dabigatran etexilate)
- Drug overview
- Clinical data
- Pharmacokinetics of BIBR-1048
- Pharmacokinetics of BIBR-953, the active form of the oral direct thrombin inhibitor BIBR-1048, in patients undergoing total hip replacement
- The effect of BIBR 953, the active form of the oral direct thrombin inhibitor BIBR-1048, on the prolongation of aPTT and ECT in orthopedic patients
- Phase II clinical trial of BIBR-1048 in MOS versus enoxaparin: BISTRO II
- Patient potential
- SPAF - greatest potential for BIBR-1048
- Potential device competitor for SPAF indication for high-risk patients?
- Marketing factors
- BIBR-1048: performance against benchmark criteria
- SWOT analysis: BIBR-1048
- Forecast to 2015
- Datamonitor comments
- 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
- Idraparinux: performance against benchmark criteria
- SWOT analysis: Idraparinux
- Forecast to 2015
- Datamonitor comments
- Overview of the key parenteral anticoagulants to be launched in acute indications
- Pipeline summary
- Datamonitor drug assessment summary
- ART-123
- Drug overview
- Clinical data
- Phase I trials
- Prevention of VTE after total hip replacement
- Patient potential
- Marketing factors
- ART-123: performance against benchmark criteria
- SWOT analysis: ART-123
- Forecast to 2015
- Datamonitor comments
- DX-9065a
- Drug overview
- Clinical data
- XaNADU-1B trial
- XaNADU-1B results
- XaNADU-ACS trial - ongoing
- DX-9065a versus Lovenox (enoxaparin)
- Patient potential
- Marketing factors
- Low predicted cost of manufacturing
- Out-licensing opportunities in US and Europe
- DX-9065a: performance against benchmark criteria
- SWOT analysis: DX-9065a
- Forecast to 2015
- Datamonitor comments
- CHAPTER 6 OTHER ANTICOAGULANTS
- ARC-183
- Drug overview
- Preclinical data
- Clinical data
- AVE-5026
- Drug overview
- AZD-0837
- Drug overview
- AZD-9684
- Drug overview
- BMS-562247 (apixaban)
- Drug overview
- DU-176b
- Drug overview
- Preclinical data
- EMD-593982
- Drug overview
- KFA-1982
- Drug overview
- LY-517717
- Drug overview
- Preclinical data
- MCC-977
- Drug overview
- Oral heparin and oral LMWH
- Drug overview
- rNAPc2
- Drug overview
- Clinical data
- Treatment of ACS
- Prevention of thromboembolism
- Other indications
- SB-424323 (odiparcil)
- Drug overview
- SCH-530348
- Drug overview
- Preclinical data
- SR-123781
- Drug overview
- Preclinical data
- SSR-126517and SSR-182289
- Drug overview
- Preclinical data
- TGN-167
- Drug overview
- TGN-255
- Drug overview
- Clinical data
- Datamonitor comments
- Tifacogin
- Drug overview
- TTP-889
- Drug overview
- XRP-0673 (otamixaban)
- Drug overview
- Preclinical data
- Clinical data
- YM-150
- Drug overview
- CHAPTER 7 ANTIPLATELETS LATE-STAGE DRUG ANALYSIS & FORECASTS
- Overview of the key pipeline antiplatelets forecast in this report
- Pipeline summary
- Datamonitor drug assessment summary
- Cangrelor (AR-C69931)
- Drug overview
- Preclinical data
- Clinical data
- Patient potential
- Marketing factors
- Cangrelor: performance against benchmark criteria
- SWOT analysis: cangrelor
- Forecast to 2015
- Datamonitor comments
- NCX-4016
- Drug overview
- Gastrointestinal safety better than aspirin
- Endogeneous formation of carcinogenic N-nitroso compounds
- Broad range of therapeutic applications beyond aspirin
- Preclinical data
- Effects of the combination of NCX 4016, aspirin and clopidogrel in a murine model of pulmonary thromboembolism
- Clinical data
- Phase I/II trial: model of systemic inflammation in healthy patients
- Phase II clinical trial in the setting of peripheral arterial disease (PAD)
- Phase II clinical trial in type 2 diabetes patients with endothelial dysfunction
- Patient potential
- Cardiovascular disease
- Potentially limited by the phenomenon of aspirin resistance
- Marketing factors
- NCX-4016: performance against benchmark criteria
- SWOT analysis: NCX-4016
- Forecast to 2015
- Datamonitor comments
- Prasugrel (CS-747)
- Drug overview
- Preclinical data
- Prasugrel in combination with aspirin
- Cerebral and peripheral arterial occlusive diseases
- Clinical data
- Randomized two-way cross-over, open-label study in healthy subjects
- Randomized, partially blind, parallel group dose-ranging Phase IIa study
- Patient potential
- Marketing factors
- Prasugrel: performance against benchmark criteria
- SWOT analysis: prasugrel
- Forecast to 2015
- Datamonitor comments
- CHAPTER 8 OTHER ANTIPLATELET AGENTS
- AZD-6140
- Drug overview
- Preclinical data
- Clinical data
- CLB-1309
- Drug overview
- Ecraprost
- Drug overview
- Clinical data
- INS-50589
- Drug overview
- Clinical data
- Liprostin
- Drug overview
- Clinical data
- Peripheral artery disease
- NM-702
- Drug overview
- Clinical data
- S-18886
- Drug overview
- Clinical data
- Preclinical data
- SL-65.0472
- Drug overview
- Preclinical data
- Xemilofiban
- Drug overview
- GPIIb/IIIa blockade by means of oral GPIIb/IIIa blockers has a long history of failure
- The BRAVO trial - confirms excess mortality associated with oral GPIIb/IIIas
- CHAPTER 9 THROMBOLYTICS LATE-STAGE DRUG ANALYSIS & FORECASTS
- Overview of the key pipeline thrombolytics forecast in this report
- Pipeline summary
- Datamonitor drug assessment summary
- Alfimeprase
- Drug overview
- Clinical data
- Phase I
- Phase II: peripheral arterial disease (PAD)
- Phase II: central venous catheter occlusion (CVCO)
- Phase III: peripheral arterial disease (PAD)
- Phase III: central venous catheter occlusion (CVCO)
- Patient potential
- Marketing factors
- Alfimeprase: performance against benchmark criteria
- SWOT analysis: alfimeprase
- Forecast to 2015
- Datamonitor comments
- Amediplase
- Drug overview
- Preclinical data
- Pharmacokinetics
- Rabbit jugular vein thrombosis model
- Rabbit ear bleeding model
- Clot penetration studies
- Clinical data
- Phase I
- Phase II/III
- Patient potential
- Marketing factors
- Amediplase: performance against benchmark criteria
- SWOT analysis: amediplase
- Forecast to 2015
- Datamonitor comments
- Desmoteplase
- Drug overview
- Preclinical data
- Pharmacokinetics
- Toxicity
- Neuroprotection
- Clinical data
- Phase I/II
- Phase II/III
- Phase II: DIAS
- Phase II: DEDAS
- Patient potential
- Marketing factors
- Desmoteplase: performance against benchmark criteria
- SWOT analysis: desmoteplase
- Forecast to 2015
- Datamonitor comments
- CHAPTER 10 OTHER THROMBOLYTIC AGENTS
- AZD-9684
- Drug overview
- HTU-PA (Hybrid-B PA)
- Drug overview
- Microplasmin
- Drug overview
- PAI-749
- Drug overview
- V-10153
- Drug overview
- Clinical data
- APPENDIX A
- Datamonitor drug assessment summary
- Contributing experts
- Bibliography
- Epidemiology
- National hospital discharge data
- General and clinical trial data
- Datamonitor reports
- 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: Developmental anticoagulants, 2005
Table 2: Developmental antiplatelets, 2005
Table 3: Developmental thrombolytics, 2005
Table 4: Developmental anticoagulants by drug class, 2005
Table 5: Developmental antiplatelets by drug class, 2005
Table 6: Developmental thrombolytics by drug class, 2005
Table 7: Developmental antithrombotics by company, 2005
Table 8: Key players in antithrombotic drug development, 2005
Table 9: Incidence of arthroplastic knee surgery (000s)
Table 10: Incidence of arthroplastic hip surgery (000s)
Table 11: Incidence of DVT, PE and VTE (000s)
Table 12: Incidence of ST-segment elevation myocardial infarction (000s)
Table 13: Incidence of unstable angina and non-ST segment elevation myocardial infarction (000s)
Table 14: Incidence of PCIs (000s)
Table 15: Incidence of stroke (000s)
Table 16: Proportion of atrial fibrillation patients at risk of developing stroke
Table 17: Prevalence of chronic atrial fibrillation (000s)
Table 18: Prevalence of PAD in the seven major markets (000s)
Table 19: Resistance to key oral antiplatelets
Table 20: Proportion of stroke patients eligible for thrombolytic therapy
Table 21: Advantages of direct thrombin inhibitors over heparin
Table 22: OASIS-5/Michelangelo trial: efficacy
Table 23: OASIS-5/Michelangelo trial: safety
Table 24: Key results of CURE sub-study
Table 25: CLARITY/TIMI-28: efficacy outcomes on angiography
Table 26: CLARITY/TIMI-28: safety outcomes
Table 27: COMMIT/CCS-2 trial: efficacy endpoints
Table 28: COMMIT/CCS-2 trial: safety endpoints
Table 29: COMMIT/CCS-2 trial: time to treatment
Table 30: COMMIT/CCS-2 trial: thrombolytic background therapy
Table 31: ARMYDA-2: number of events at 30 days
Table 32: ARMYDA-2: postprocedural peak biomarker levels
Table 33: ARMYDA-2: percentage of patients with an elevation of CKMB/troponin I
Table 34: ARMYDA-2: number of bleeding events at 30 days
Table 35: Comparison of tPA-based thrombolytics
Table 36: Key efficacy endpoints used in anticoagulant clinical trials
Table 37: Key safety endpoints used in anticoagulant clinical trials
Table 38: Profiled key anticoagulants (long-term indications), 2005
Table 39: Research, clinical and commercial attractiveness summary for key anticoagulants to be launched in long-term settings
Table 40: Global sales forecasts for BAY-597939, 2008-15
Table 41: Proportion of AF patients receiving antithrombotic therapy by level of risk of experiencing stroke
Table 42: Global sales forecasts for BIBR-1048, 2008-15
Table 43: Comparison of fondaparinux with idraparinux
Table 44: PERSIST trial results
Table 45: Global sales forecasts for idraparinux, 2007-15
Table 46: Key parenteral anticoagulants (acute indications), 2005
Table 47: Research, clinical and commercial attractiveness summary for key anticoagulants to be launched in acute settings
Table 48: Result of dose-response trial examining ART-123
Table 49: Global sales forecasts for ART-123, 2007-15
Table 50: Prothrombin F1.2 levels at baseline and after 72 hours
Table 51: Global sales forecasts forDX-9065a, 2007-15
Table 52: Key pipeline antiplatelets, 2005
Table 53: Research, clinical and commercial attractiveness summary for key late-phase pipeline antiplatelets
Table 54: Global sales forecasts for cangrelor, 2008-15
Table 55: Global sales forecasts for NCX-4016, 2008-15
Table 56: Comparison of antiplatelet, antithrombotic, and antihemostatic effects of prasugrel, clopidogrel and ticlopidine
Table 57: Number of adverse events
Table 58: JUMBO-TIMI 26: patient characteristics
Table 59: JUMBO-TIMI 26: primary endpoint (significant bleeding)
Table 60: JUMBO-TIMI 26: TIMI major bleeding
Table 61: JUMBO-TIMI 26: total bleeding episodes (TIMI major/minor and minimal)
Table 62: JUMBO-TIMI 26: secondary endpoint (MACE)
Table 63: JUMBO-TIMI 26: MACE components
Table 64: Global sales forecasts for prasugrel, 2008-15
Table 65: Results of the NM-702 Phase IIa study
Table 66: Discontinued oral GPIIb/IIIa inhibitor pipeline
Table 67: Summary of GPIIb/IIIa inhibitor trial failures
Table 68: Key pipeline thrombolytics, 2005
Table 69: Research, clinical and commercial attractiveness summary for key pipeline thrombolytics
Table 70: Global sales forecasts for alfimeprase, 2009-15
Table 71: Global sales forecasts for amediplase, 2009-15
Table 72: DEDAS: safety endpoints
Table 73: Global sales forecasts for desmoteplase, 2007-15
Table 74: Datamonitor drug assessment parameters
List of Figures
Figure 1: Antithrombotics pipeline, 2005
Figure 2: Developmental antithrombotics by company type, 2005
Figure 3: Overlap of ischemic cardiovascular conditions
Figure 4: Frequency of disease with symptoms in the three organ systems and their overlap, from the CAPRIE trial
Figure 5: Risk of stroke increases with age
Figure 6: Breakdown of the PAD population by classification
Figure 7: The targets of developmental anticoagulants and selected thrombolytics
Figure 8: Indication roll-out for Lovenox (enoxaparin)
Figure 9: Aspirin inhibits platelet COX-1 irreversibly
Figure 10: The role of purinergic receptors as targets for antiplatelets
Figure 11: GP IIb/IIIa receptor antagonists act directly on the receptor
Figure 12: CLARITY/TIMI-28: study design
Figure 13: COMMIT/CCS-2 trial: dual antiplatelet therapy in AMI
Figure 14: ARMYDA-2: trial design
Figure 15: Research, clinical and commercial attractiveness summary for key anticoagulants to be launched in long-term settings
Figure 16: Research, clinical and commercial attractiveness summary for key anticoagulants to be launched in long-term settings
Figure 17: Performance against benchmark criteria: BAY-597939
Figure 18: SWOT analysis: BAY-597939
Figure 19: Global sales forecasts for BAY-597939, 2008-15
Figure 20: Performance against benchmark criteria: BIBR-1048
Figure 21: SWOT analysis: BIBR-1048
Figure 22: Global sales forecasts for BIBR-1048, 2008-15
Figure 23: PERSIST trial design
Figure 24: Idraparinux Phase III program: VAN GOGH
Figure 25: Idraparinux Phase III program: AMADEUS
Figure 26: Is recombinant factor VIIa a valid antidote to idraparinux?
Figure 27: Performance against benchmark criteria: idraparinux
Figure 28: SWOT analysis: idraparinux
Figure 29: Global sales forecasts for idraparinux, 2007-15
Figure 30: Research, clinical and commercial attractiveness summary for key anticoagulants to be launched in acute settings
Figure 31: Research, clinical and commercial attractiveness summary for key anticoagulants to be launched in acute settings
Figure 32: Performance against benchmark criteria: ART-123
Figure 33: SWOT analysis: ART-123
Figure 34: Global sales forecasts for ART-123, 2007-15
Figure 35: Performance against benchmark criteria: DX-9065a
Figure 36: SWOT analysis: DX-9065a
Figure 37: Global sales forecasts forDX-9065a, 2007-15
Figure 38: Research, clinical and commercial attractiveness summary for key late-phase pipeline antiplatelets
Figure 39: Research, clinical and commercial attractiveness summary for key late-phase pipeline antiplatelets
Figure 40: Phase II: cangrelor vs. abciximab in the setting of PCI
Figure 41: Performance against benchmark criteria: cangrelor
Figure 42: SWOT analysis: cangrelor
Figure 43: Global sales forecasts for cangrelor, 2008-15
Figure 44: Performance against benchmark criteria: NCX-4016
Figure 45: SWOT analysis: NCX-4016
Figure 46: Global sales forecasts for NCX-4016, 2007-15
Figure 47: Randomized two-way cross-over study in healthy subjects
Figure 48: Randomized, partially blind, parallel group dose-ranging study
Figure 49: JUMBO-TIMI 26: prasugrel in the setting of PCI
Figure 50: TRITON-TIMI-38: trial design
Figure 51: Performance against benchmark criteria: prasugrel
Figure 52: SWOT analysis: prasugrel
Figure 53: Global sales forecasts for prasugrel, 2008-15
Figure 54: AZD-6140 is a potent inhibitor of platelet aggregation
Figure 55: Research, clinical and commercial attractiveness summary for key antiplatelets to be launched in acute settings
Figure 56: Research, clinical and commercial attractiveness summary for key pipeline thrombolytics
Figure 57: Performance against benchmarking criteria: alfimeprase
Figure 58: SWOT analysis: alfimeprase
Figure 59: Global sales forecasts for alfimeprase, 2009-15
Figure 60: Performance against benchmarking criteria: amediplase
Figure 61: SWOT analysis: amediplase
Figure 62: Global sales forecasts for amediplase, 2009-15
Figure 63: Performance against benchmark criteria: desmoteplase
Figure 64: SWOT analysis: desmoteplase
Figure 65: Global sales forecasts for desmoteplase, 2007-15
Figure 66: Example of Datamonitor drug assessment scorecard
Figure 67: Example of Datamonitor drug assessment graphAbstractIntroduction
Datamonitor estimates the total revenue generated from new antithrombotics in the seven major markets will reach approximately $10bn by 2015, with novel oral anticoagulants contributing over 70% to this volume. However, barriers to entry exist and developmental antithrombotics must pursue an aggressive development strategy to compete successfully with well-established gold-standard therapies.
Scope
- Assessment of the patient potential for developmental antithrombotics in the major thrombosis indications over the period 2005-15
- Overview of the antithrombotic R&D pipeline with detailed information on the classes in development
- Commercial analysis of key compounds in development in terms of their ability to satisfy unmet needs, supported by the views of key opinion leaders
- Sales forecasts for key late-stage developmental antithrombotics in the seven major markets to 2015
Highlights
After the demise of AstraZeneca's anticoagulant Exanta, Boehringer Ingelheim's BIBR-1048 and Bayer's BAY-597939 are next in line with a chance to switch warfarin-treated patients and grow the market by recruiting the previously untreated population.
Prasugrel and cangrelor are the most promising developmental antiplatelets with the potential to successfully challenge established drugs such as clopidogrel and GPIIb/IIIa blockers.
Developmental thrombolytics hold little commercial promise because of established competitors, niche-focused launch strategies, and the overall decline of the thrombolytics market, driven by the increase in cardiovascular surgery.
Reasons to Purchase
- Understand the key factors that will contribute to the success of the next generation of antithrombotics
- Assess and beat the barriers to entry created by the lifecycle strategies of existing market players
- Find out what market opportunities remain where developmental anticoagulants, antiplatelets and thrombolytics are unable to fulfill unmet needs
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