Stroke remains the leading cause of disability and the third leading cause of death in the developed world. Scrip's report describes current strategies for the prevention and treatment of stroke, and looks in detail at drugs in development for this devastating condition.

A major recent advance is thrombolytic therapy for acute ischaemic stroke: Scrip's report covers this in detail. Established drugs such as aspirin, dipyridamole and heparin are discussed alongside new candidates including neuroprotective agents. The pathophysiology of stroke and the major risk factors are reviewed, and useful definitions are given.

The report also includes a detailed analysis of the stroke market, with emphasis on the likely impact of emerging drugs.

In addition, detailed profiles are provided of the key companies involved in this important area, including: Boehringer Ingelheim; Genentech; Interneuron; Janssen; Knoll; Roche.

PUBLICATION: FEBRUARY 1998
REF: BS912E
PAGES: 150+
PRICE: £495/$1,040/¥119,000

SEE ALSO:
Atherosclerosis: Developments and opportunities
Antiplatelet Agents: The rise of the superaspirin?
Hypertension: Therapeutic advances and market opportunities

CHAPTER 1 INTRODUCTION
1.1 Definitions
1.1.1 Ischaemic stroke
1.1.2 Haemorrhagic stroke
1.1.3 ICH: the 'forgotten stroke'
1.2 Symptoms of stroke
1.3 Diagnosis of stroke
1.4 Transient ischaemic attacks and silent ischaemia
1.5 Traumatic brain injury
1.6 Emergency treatment of stroke
1.7 Incidence of stroke
1.7.1 Age
1.7.2 An ageing population
1.7.3 Sex
1.7.4 Race
1.8 Deaths caused by stroke
1.9 Disability and rehabilitation
1.9.1 Dementia
1.10 Pathophysiology of stroke
1.10.1 Drug targets
1.11 Risk factors for stroke
1.11.1 Atrial fibrillation
1.11.2 Cholesterol
1.11.3 Hypertension
1.11.4 Atherosclerosis
1.11.5 Heart disease
1.11.6 Diabetes
1.11.7 Oral contraceptives
1.11.8 Hormone replacement therapy
1.11.9 Smoking
1.11.10 Alcohol
1.11.11 TIAs or history of stroke
1.11.12 Homocysteine
1.12 Prevention and treatment of stroke
1.12.1 Non-pharmacological approaches
1.12.2 Pharmacological approaches
1.12.3 Surgical approaches
1.13 Models of stroke
1.14 UK stroke care
1.15 US perspective
1.16 Provision of stroke care
1.17 The cost of stroke
1.17.1 Funding
1.18 Conclusions

CHAPTER 2 THE MANAGEMENT OF STROKE - AVAILABLE THERAPIES
2.1 Introduction
2.2 Prevention of stroke
2.2.1 Antiplatelets
2.2.1.1 Aspirin
2.2.1.2 Clopidogrel
2.2.1.3 Dipyridamole
2.2.1.4 Ticlopidine
2.2.2 Anticoagulants
2.2.2.1 Warfarin
2.2.2.2 Guidelines for oral anticoagulants
2.2.2.3 INR system
2.2.3 Surgery
2.2.4 Antihypertensives
2.3 Acute treatment of stroke
2.3.1 Antiplatelets
2.3.1.1 Aspirin
2.3.2 Anticoagulants
2.3.2.1 Heparin
2.3.3 Thrombolytic therapy
2.3.3.1 Alteplase (tPA)
2.3.3.2 Guidelines for thrombolytic therapy
2.3.4 Surgery
2.4 Conclusions

CHAPTER 3 THE MANAGEMENT OF STROKE - EMERGING THERAPIES
3.1 Introduction
3.2 Neuroprotectives
3.2.1 Calcium channel blockers
3.2.1.1 Calpain inhibitors
3.2.1.2 Felodipine
3.2.1.3 Lacidipine
3.2.1.4 Lemildipine
3.2.1.5 Magnesium
3.2.1.6 Nilvadipine
3.2.1.7 Nimodipine
3.2.1.8 Nisoldipine
3.2.1.9 SNX-111
3.2.1.10 Others
3.2.2 Inhibitors of the actions of toxic neurotransmitters
3.2.2.1 Aptiganel HCl (Cerestat)
3.2.2.2 AR-R15896AR
3.2.2.3 BAY-x-3702
3.2.2.4 BI-II-277-CL
3.2.2.5 CGP 63446
3.2.2.6 Clomethaziole
3.2.2.7 CNS-5161
3.2.2.8 CP-101606
3.2.2.9 Dextrorphan
3.2.2.10 Eliprodil
3.2.2.11 Fosphenytoin
3.2.2.12 Ganaxolone
3.2.2.13 GV-150526
3.2.2.14 GV-196771
3.2.2.15 Licostinel (ACEA 1021)
3.2.2.16 Lubeluzole
3.2.2.17 NBQX
3.2.2.18 NNC 07-0775
3.2.2.19 NPS-1506
3.2.2.20 NS-409
3.2.2.21 PNU-101017
3.2.2.22 Protara
3.2.2.23 Remacemide
3.2.2.24 Selfotel
3.2.2.25 ZD-9379
3.2.2.26 Others
3.2.3 Immunological agents
3.2.3.1 Enlimomab
3.2.3.2 Hu23F2G
3.2.3.3 SMART anti-E/P-selectin antibody
3.2.3.4 SMART anti-L-selectin antibody
3.2.4 Cytokine-mediated drugs and related products
3.2.4.1 AF-1
3.2.4.2 F-spondin
3.2.4.3 Neurturin
3.2.4.4 Neutrophil inhibitory factor
3.2.4.5 Nerve growth factor, Genentech
3.2.4.6 Neurotrophin-3
3.2.4.7 Trafermin
3.2.4.8 Others
3.2.5 Agents which scavenge or prevent formation of free radicals
3.2.5.1 Nitrone-related therapeutics
3.2.5.2 Tirilazad mesylate
3.2.6 Agents targeted at nitric oxide
3.2.6.1 ARL-16556
3.2.6.2 NitroMed
3.2.7 Agents which protect cell membranes
3.2.7.1 Citicoline
3.2.8 Other neuroprotective strategies
3.3 Thrombolytics
3.3.1 TNK-tPA
3.3.2 Reteplase
3.3.3 Other tPAs
3.3.4 Streptokinase
3.3.5 Pro-urokinase
3.4 Anticoagulants
3.4.1 Argatroban
3.4.2 Dalteparin
3.4.3 Enoxaparin
3.4.4 Nadroparin
3.4.5 Org 10172
3.4.6 Ancrod
3.4.7 PAI-1 inhibitors
3.5 Antiplatelets
3.5.1 gpIIb/IIIa antiplatelet agents
3.5.1.1 GPI 562
3.5.1.2 Integrilin
3.5.1.3 Lamifiban
3.5.1.4 Lefradafiban
3.5.1.5 Orbofiban
3.5.1.6 ReoPro
3.5.1.7 Ro-48-3657
3.5.1.8 RPR-10981
3.5.1.9 Sibrafiban
3.5.1.10 Tirofiban
3.5.1.11 Xemilofiban hydrochloride
3.5.2 Isbogrel
3.6 Cholesterol-lowering agents
3.6.1 HMG-CoA reductase inhibitors (statins)
3.6.1.1 Atorvastatin
3.6.1.2 Cerivastatin
3.6.1.3 Fluvastatin
3.6.1.4 Pravastatin
3.7 Tissue regeneration strategies
3.7.1 Cell therapy
3.7.2 Creative BioMolecules
3.8 Other companies/collaborations
3.8.1 Allergan
3.8.2 Biorex
3.8.3 Pharmacopeia and Texas Biotechnology
3.8.4 Vascular Therapeutics
3.9 Conclusions

CHAPTER 4 MARKET INFORMATION
4.1 Introduction
4.2 The world market for cardiovascular and CNS drugs
4.3 Top companies in stroke R&D
4.4 Neuroprotectives
4.5 Thrombolytics
4.6 Antithrombotics
4.6.1 Antiplatelets
4.6.2 Anticoagulants
4.7 Summary of sales figures
4.8 Cholesterol-lowering drugs
4.8.1 Cost comparisons for leading statins
4.9 Antihypertensives
4.10 Conclusions

CHAPTER 5 COMPANY PROFILES
5.1 American Home Products
5.2 Astra
5.3 Bayer
5.4 Boehringer Ingelheim
5.5 Bristol-Myers Squibb
5.6 Cambridge NeuroScience
5.7 CoCensys
5.8 Genentech
5.9 Glaxo Wellcome
5.10 Interneuron
5.11 Johnson & Johnson
5.12 Neurex
5.13 Novartis
5.14 Pfizer
5.15 Pharmacia & Upjohn
5.16 Roche
5.17 Sanofi
5.18 Takeda
5.19 Warner-Lambert

CHAPTER 6 DIRECTORY

REFERENCES

APPENDIX 1 EXCHANGE RATES

List of tables
Table 1.1 Risk factors for stroke
Table 1.2 Estimated direct and indirect costs of stroke, US 1997

Table 3.1 Examples of neuroprotective compounds
Table 3.2 Some NMDA antagonists in development
Table 3.3 Neuroprotective drugs which inhibit the actions of toxic neurotransmitters

Table 4.1 Sales of cardiovascular and CNS drugs by major geographical region, September 1996 to August 1997
Table 4.2 Top companies with compounds in development for stroke, and number of compounds in each phase
Table 4.3 Estimated and projected sales figures for marketed and potential drugs for the management of stroke
Table 4.4 Sales figures for selected statin drugs
Table 4.5 WAC of leading statin drugs

Table 5.1 American Home Products' financial results, nine months ended 30 September 1997 and same period for 1996
Table 5.2 American Home Products' financial results, 12 months ended 31 December 1995 and 1996
Table 5.3 American Home Products' sales by region, 1996
Table 5.4 Astra's financial results, 1996-1997
Table 5.5 Astra's sales by product group, first nine months 1997 and 1996, and full year 1996 (SKr million)
Table 5.6 Astra's sales by region, 1996
Table 5.7 Bayer's financial results, first nine months of 1997 and of 1996
Table 5.8 Boehringer Ingelheim's financial results, 1995-1996
Table 5.9 Bristol-Myers Squibb's financial results for the first nine months of 1997
Table 5.10 Cambridge NeuroScience's financial results, 1996 and 1997
Table 5.11 CoCensys' financial results, first nine months of 1997 and of 1996
Table 5.12 Genentech's financial results, 12 months ended 31 December 1996 and 1997
Table 5.13 Glaxo Wellcome's financial results, six months to 30 June 1997 and 1996
Table 5.14 Glaxo Wellcome's sales by region, six months to 30 June 1997
Table 5.15 Glaxo Wellcome's financial results, full year ended 31 December 1996 and 1995
Table 5.16 Interneuron's financial results, 12 months ended 30 September 1997 and 1996
Table 5.17 Johnson & Johnson's financial results for the first nine months of 1997 and 1996
Table 5.18 Neurex's financial results, first nine months 1997 and 1996
Table 5.19 Neurex's financial results, 12 months ended 31 December
Table 5.20 Novartis' nine-month sales, 1997 and 1996, by division
Table 5.21 Novartis' financial results, 1995-1996
Table 5.22 Pfizer's financial results, nine months ended 30 September 1996 and 1997
Table 5.23 Pfizer's financial results, 1994-1996
Table 5.24 Pharmacia & Upjohn's financial results, first nine months 1997 and 1996
Table 5.25 Roche's sales by division, full year 1997
Table 5.26 Roche's financial results, 1995-1996
Table 5.27 Sanofi's financial results, 1995-1996
Table 5.28 Takeda's first-half financial results to 30 September 1997
Table 5.29 Takeda's financial results, 1993-1997
Table 5.30 Warner-Lambert's nine-month financial results, 1996 and 1997
Table 5.31 Warner-Lambert's financial results, 1995-1996

List of figures
Figure 1.1 Frequency of stroke by type
Figure 1.2 Estimated prevalence of stroke by age and sex, US 1988-1991
Figure 1.3 Deaths per 100,000 population in the US, by sex and race (1993)
Figure 1.4 Functional outcome of patients an average of seven years following stroke

Figure 4.1 Sales of cardiovascular and CNS drugs by major geographical region, September 1996 to August 1997
Figure 4.2 Wholesale costs of antihypertensive drugs in the US, 1992-1995

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