Therapeutic Advances in Neurodegenerative Diseases: Unlocking market opportunities

Therapeutic Advances in Neurodegenerative Diseases: Unlocking market opportunities

Therapeutic

The neurodegenerative disorder market is in desperate need of therapies to cure or modify diseases, rather than just merely treating disease symptoms.

This report looks at the commercial potential afforded by this major healthcare area. With an ageing global population resulting in a rapidly expanding market base, the unmet needs of these illnesses must be tackled soon.

This invaluable guide profiles current therapies and exciting products in R&D looking to overcome the problems associated with existing drugs, particularly the distressing side-effects.

Focusing on the potential of disease modifying products for Alzheimer's and Parkinson's disease and with first-hand interviews from the 53rd Annual Meeting of the American Academy of Neurology, this study answers, amongst others, the following questions:

What size is the market for neurodegenerative diseases?
Which sectors have the greatest potential for growth?
How will novel products be positioned in the market?
What are the pitfalls / potential rewards for R&D in this sector?

Published: July 2001
Pages: 183
Ref: BS1131E
Price: £495/$1,040/¥119,000

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CONTENTS
LIST OF TABLES
LIST OF FIGURES
EXECUTIVE SUMMARY
ABBREVIATIONS

CHAPTER 1 INTRODUCTION TO NEURODEGENERATIVE DISORDERS
1.1 Definition of neurodegenerative disorders
1.2 Types of neurodegenerative disorders
1.2.1 Alzheimer's disease
1.2.1.1 Symptoms of Alzheimer's disease
1.2.1.2 Diagnosis of Alzheimer's disease
1.2.1.3 Prevalence of Alzheimer's disease and economic cost
1.2.1.4 Pathology of Alzheimer's disease
1.2.1.5 Epidemiology of Alzheimer's disease
1.2.2 Other dementias
1.2.2.1 Vascular dementia
1.2.2.2 Dementia with Parkinsonism
1.2.2.3 Dementia associated with AIDS
1.2.2.4 Creutzfeldt-Jakob disease
1.2.2.5 Hydrocephalus
1.2.3 Parkinson's disease
1.2.3.1 Symptoms of Parkinson's disease
1.2.3.2 Diagnosis of Parkinson's disease
1.2.3.3 Prevalence of Parkinson's disease and economic cost
1.2.3.4 Pathology of Parkinson's disease
1.2.3.5 Mechanisms of neurodegeneration in Parkinson's disease
1.2.3.6 Pathophysiology of Parkinson's disease
1.2.3.7 Epidemiology of Parkinson's disease
1.2.4 Other movement disorders
1.2.4.1 Huntingdon's disease
1.2.5 Neuropathies
1.2.6 Multiple sclerosis and amyotrophic lateral sclerosis
1.2.6.1 Multiple sclerosis
1.2.6.2 Amyotrophic lateral sclerosis
1.3 Management of Alzheimer's and other dementias
1.3.1 Treatment of behavioural problems associated with Alzheimer's disease
1.3.2 Slowing the progression of Alzheimer's disease
1.4 Management of Parkinson's disease and other movement disorders
1.4.1 Surgical approaches to the treatment of Parkinson's disease
1.4.1.1 Stereotactic surgery
1.4.1.2 Deep-brain stimulation
1.4.1.3 Neurotransplantation
1.4.2 Treatment of mental disturbances in Parkinson's disease
1.4.3 Dementia and cognitive function in Parkinson's disease
1.4.4 Management of Huntington's disease
1.4.4.1 Neural transplantation in the management of Huntington's disease
1.5 Management of diabetic neuropathy and other peripheral neuropathic conditions
1.6 Management of multiple sclerosis and ALS
1.6.1 Multiple sclerosis
1.6.1.1 Treatment of complication associated with multiple sclerosis
1.6.2 Management of amyotrophic lateral sclerosis

CHAPTER 2 PRODUCTS ON THE MARKET FOR NEURODEGENERATIVE DISORDERS
2.1 Alzheimer's disease/dementia
2.1.1 Cholinesterase inhibitors
2.1.1.1 Donepezil
2.1.1.2 Galantamine
2.1.1.3 Rivastigmine
2.1.1.4 Tacrine
2.2 Parkinson's disease/movement disorders
2.2.1 Levodopa
2.2.1.1 Levodopa + beserazide
2.2.1.2 Levodopa + carbidopa
2.2.2 COMT inhibitors
2.2.2.1 Entacapone
2.2.3 MAO-B inhibitors
2.2.3.1 Selegiline
2.2.4 Dopamine agonists
2.2.4.1 Apomorphine
2.2.4.2 Bromocriptine
2.2.4.3 Cabergoline
2.2.4.4 Pergolide
2.2.4.5 Pramipexole
2.2.4.6 Ropinirole
2.2.5 Anticholinergics
2.3 Huntington's disease
2.4 Multiple sclerosis and ALS
2.4.1 Multiple sclerosis
2.4.1.1 Treatment of relapses in multiple sclerosis
2.4.1.2 Treatment of relapsing-remitting multiple sclerosis
2.4.1.3 Secondary progressive multiple sclerosis
2.4.2 Amyotrophic lateral sclerosis
2.5 Conclusion

CHAPTER 3 PRODUCTS FOR NEURODEGENERATIVE DISEASES IN R&D
3.1 Alzheimer's disease/dementia
3.1.1 Cholinergic neurotransmission enhancers/agonists
3.1.1.1 Cholinesterase inhibitors
3.1.1.2 Acetylcholine release stimulants
3.1.1.3 Choline uptake stimulants
3.1.1.4 Acetylcholine agonists
3.1.1.5 Muscarinic agonists
3.1.2 Serotonin neurotransmission enhancers/agonists
3.1.3 AMPA receptor agonists
3.1.4 Other neurotransmitter modulators
3.1.4.1 GABA receptor agonists
3.1.4.2 MAO-B inhibitors
3.1.4.3 NMDA receptor antagonists
3.1.5 Amyloid plaque formation inhibitors
3.1.6 Anti-inflammatories
3.1.6.1 Non-steroidal anti-inflammatory drugs
3.1.7 Neurotrophic factor
3.1.8 Others
3.1.8.1 Statins
3.1.8.2 Neural transplant for Alzheimer's disease
3.2 Parkinson's disease/movement disorders
3.2.1 Dopamine agonists
3.2.2 MAO-B inhibitors
3.2.3 NMDA antagonists
3.2.4 Adenosine A2a receptor antagonists
3.2.5 Others
3.2.5.1 Neural cell transplants
3.2.5.2 Treatment of dementia in Parkinson's disease
3.2.6 Stem cell research
3.2.6.1 In vitro generation of human CNS precursors
3.2.7 Huntington's disease
3.3 Neuropathies
3.3.1 Aldose reductase inhibitors
3.3.2 ACE inhibitors
3.3.3 Others
3.4 Multiple sclerosis/amyotrophic lateral sclerosis
3.4.1 Drugs in clinical development for multiple sclerosis
3.4.1.1 Immunomodulators
3.4.1.2 Cannabinoid agonists
3.4.1.3 Others
3.4.2 Drugs in development for amyotrophic lateral sclerosis

CHAPTER 4 NEURODEGENERATIVE DISEASE MARKET
4.1 Introduction
4.1.1 Worldwide pharmaceutical market
4.2 Neurodegenerative disease market
4.2.1 Market for Alzheimer's/dementia drugs
4.2.1.1 Incidence of Alzheimer's disease in major markets
4.2.1.2 Current value of Alzheimer's disease market
4.2.1.3 Potential of Alzheimer's disease market
4.2.2 Market for Parkinson's disease/movement disorders
4.2.2.1 Incidence of Parkinson's disease in major markets
4.2.2.2 Current value of Parkinson's disease market
4.2.2.3 Potential of Parkinson's disease market
4.2.3 Market for multiple sclerosis/amyotrophic lateral sclerosis
4.2.3.1 Current value of multiple sclerosis/amyotrophic lateral sclerosis market
4.2.4 Incidence of multiple sclerosis/amyotrophic lateral sclerosis
4.2.4.1 Incidence of multiple sclerosis in major markets
4.2.4.2 Incidence of amyotrophic lateral sclerosis
4.2.5 Market for diabetic neuropathy treatments
4.3 Conclusion

CHAPTER 5 PROFILES OF SELECTED COMPANIES
5.1 Axonyx
5.1.1 Agreements re neurodegenerative therapy
5.1.2 Financial highlights
5.1.3 Neurodegenerative portfolio/pipeline
5.2 Biogen
5.2.1 Agreements re neurodegenerative therapy
5.2.2 Financial highlights
5.2.3 Neurodegenerative drug portfolio/pipeline
5.3 Diacrin
5.3.1 Agreements re neurodegenerative therapy
5.3.2 Financial highlights
5.3.3 Neurodegenerative portfolio/pipeline
5.4 DuPont
5.4.1 Agreements re neurodegenerative therapy
5.4.2 Financial highlights
5.4.3 Neurodegenerative drug portfolio/pipeline
5.5 Eisai Co Ltd
5.5.1 Agreements re neurodegenerative therapy
5.5.2 Financial highlights
5.5.3 Neurodegenerative drug portfolio/pipeline
5.6 Elan Corporation
5.6.1 Agreements re neurodegenerative therapy
5.6.2 Financial highlights
5.6.3 Neurodegenerative drug portfolio/pipeline
5.7 Immune Network Research Ltd
5.7.1 Financial highlights
5.7.2 Neurodegenerative drugs portfolio/pipeline
5.8 Johnson & Johnson
5.8.1 Agreements re neurodegenerative therapy
5.8.2 Financial highlights
5.8.3 Neurodegenerative drug portfolio/pipeline
5.9 Eli Lilly
5.9.1 Agreements re neurodegenerative therapy
5.9.2 Financial highlights
5.9.3 Neurodegenerative portfolio/pipeline
5.10 NeoTherapeutics
5.10.1 Financial highlights
5.10.2 Neurodegenerative drugs portfolio/pipeline
5.11 Novartis
5.11.1 Agreements re neurodegenerative therapy
5.11.2 Financial highlights
5.11.3 Neurodegenerative drug portfolio/pipeline
5.12 Orion Pharma
5.12.1 Agreements re neurodegenerative therapy
5.12.2 Financial highlights
5.12.3 Neurodegenerative drug portfolio/pipeline
5.13 Pfizer
5.13.1 Agreements re neurodegenerative therapy
5.13.2 Financial highlights
5.13.3 Neurodegenerative drug portfolio/pipeline
5.14 Pharmacia Corporation
5.14.1 Agreements re neurodegenerative therapy
5.14.2 Financial highlights
5.14.3 Neurodegenerative drugs portfolio/pipeline
5.15 Roche
5.15.1 Agreements re neurodegenerative therapy
5.15.2 Financial highlights
5.15.3 Neurodegenerative drugs portfolio/pipeline
5.16 Sanofi-Synth�labo
5.16.1 Agreements re neurodegenerative therapy
5.16.2 Financial highlights
5.16.3 Neurodegenerative drug portfolio/pipeline
5.17 Serono Group
5.17.1 Agreements re neurodegenerative therapy
5.17.2 Financial highlights
5.17.3 Neurodegenerative portfolio/pipeline
5.18 Teva
5.18.1 Agreements re neurodegenerative therapy
5.18.2 Financial highlights
5.18.3 Neurodegenerative drug portfolio/pipeline

CHAPTER 6 DIRECTORY

REFERENCES
FURTHER READING

LIST OF TABLES
Table 1.1 Genes involved in the pathogenesis of Alzheimer's disease
Table 1.2 Examples of vascular disorders that can cause dementia
Table 1.3 Physical abnormalities associated with Parkinson's disease
Table 1.4 Summary of mechanisms and factors involved in secondary parkinsonism
Table 1.5 Gene loci associated with Parkinson's disease
Table 1.6 Classification of forms of multiple sclerosis
Table 2.1 Summary of cholinesterase inhibitor products on the market for Alzheimer's disease (as at April 2001)
Table 2.2 Summary of drug classes marketed for the treatment of Parkinson's disease
Table 2.3 Summary of marketed dopaminergic drugs
Table 2.4 Treatment options for Huntington's disease
Table 2.5 Summary of current treatment options for multiple sclerosis
Table 3.1 Products in preclinical development for Alzheimer's disease/dementia
Table 3.2 Summary of cholinergic neurotransmission enhancers/agonists in development for Alzheimer's disease
Table 3.3 Summary of serotonin neurotransmission enhancers/agonists in development for Alzheimer's disease
Table 3.4 Summary of other drugs in development for Alzheimer's disease
Table 3.5 Products in preclinical development for Parkinson's disease
Table 3.6 Dopamineric drugs in development for Parkinson's disease
Table 3.7 Summary of other mechanisms in development for Parkinson's disease
Table 3.8 Drugs in development for Huntington's disease
Table 3.9 Drugs in preclinical development for diabetic neuropathy
Table 3.10 Aldose reductase inhibitors in clinical development for diabetic neuropathy
Table 3.11 Summary of other drugs in development for diabetic neuropathy
Table 3.12 Products in preclinical development for multiple sclerosis
Table 3.13 Drugs in clinical development for amyotrophic lateral sclerosis
Table 4.1 Sales and NPV comparison in CNS and other selected therapeutic categories ($ million), 1997�2002
Table 4.2 Comparison of CNS market value and total pharmaceutical sales of leading companies in the CNS sector, 1999
Table 4.3 Prevalence of select causes of adult-onset brain impairment in the US, 1998
Table 4.4 Ageing demographics in selected countries
Table 4.5 Sales in the Alzheimer's disease market ($ million), 1998�2002
Table 4.6 Value of the Alzheimer's disease market by selected company ($ million), 1999�2002
Table 4.7 Incidence of Parkinson's disease by geographic region, 1996
Table 4.8 Global comparison of mortality rates for Parkinson's disease, 1996
Table 4.9 Average annual mortality rates in Canada for Parkinson's disease by sex, 1977�1996
Table 4.10 Sales of specific drugs in the Parkinson's disease market ($ million), 1998�2002
Table 4.11 Parkinson's disease market value by selected company ($ million), 1999�2002
Table 4.12 Sales of specific drugs in the multiple sclerosis/ALS market ($ million), 1998�2001
Table 4.13 Multiple sclerosis/ALS market value by selected company ($ million), 1999�2002
Table 4.14 Incidence of multiple sclerosis by geographic region, 1996
Table 4.15 Estimated future prevalence of diabetes in five key European markets, 2000�2010
Table 5.1 Axonyx's financial results ($), 1999�2000
Table 5.2 Biogen's financial results ($ thousand), 1998�2000
Table 5.3 Diacrin's financial results ($ thousand), 1998�2000
Table 5.4 DuPont Pharmaceutical's financial results ($ million), 1998�2000
Table 5.5 Eisai's financial results (¥ billion), 1999�2001
Table 5.6 Eisai's leading domestic pharmaceutical products (¥ billion), 1999�2000
Table 5.7 Elan's financial results ($ thousand), 1999�2000
Table 5.8 Sales of Elan's top products, 2000
Table 5.9 Immune Network's financial results ($), 1998�2000
Table 5.10 Johnson & Johnson's financial results ($ million), 1998�2000
Table 5.11 Sales of selected Johnson & Johnson pharmaceutical products ($ million), 1999�2000
Table 5.12 Lilly's financial results ($ million), 1998�2000
Table 5.13 NeoTherapeutics' financial results ($ thousand), 1998�2000
Table 5.14 Novartis' financial results (SwFr million), 1998�2000
Table 5.15 Novartis' top 20 pharmaceutical products (SwFr million), 1999�2000
Table 5.16 Orion's financial results (Euro million), 1999�2000
Table 5.17 Pfizer's financial results ($ million), 1998�2000
Table 5.18 Pfizer's sales by therapy area and product ($ million), 1999�2000
Table 5.19 Pharmacia's financial results ($ million), 1998�2000
Table 5.20 Roche's financial results (SwFr million), 1998�2000
Table 5.21 Roche's sales by region, 2000
Table 5.22 Sanofi-Synth�labo's financial results (Euro million), 1998�2000
Table 5.23 Serono's financial results ($ million), 1999�2000
Table 5.24 Serono's sales by geographic region ($ million), 1999�2000
Table 5.25 Teva's financial results ($ thousand), 1998�2000

LIST OF FIGURES
Figure 1.1 Schematic representation of the direct and indirect GABAergic pathways for dopamine deficiency
Figure 4.1 Pharmaceutical sales in key markets, year to September 2000
Figure 4.2 Pharmaceutical sales by therapeutic category, year to September 2000
Figure 4.3 Sales in the neurodegenerative market for leading companies, 2000
Figure 4.4 Aricept sales by region, 1999�2002
Figure 4.5 Sales Avonex by region, 1999�2002
Figure 4.6 US and non-US sales of Rilutek, 1999�2000
Figure 4.7 Global estimates of diabetes, 2000

Executive Summary
With the baby-boomer generation progressing towards retirement age, the issue of age-related disorders is rapidly growing in importance. Two major neurodegenerative diseases, Parkinson's disease and Alzheimer's disease, both have highly significant age-related risk factors. In the US over-65 population, 10% of individuals have Alzheimer's disease, which rises to 50% in the over-85 population. For Parkinson's disease, one in 100 Americans over the age of 60 is affected, but this rate is 3�4 times higher in the over-75 population. Moreover, advances in medical science have resulted in people living longer � less people die from heart attacks or cancer in their fifties and sixties. Instead, a greater proportion of the population are reaching their 70th, 80th and even 90th birthday and beyond. These figures point to major healthcare concerns. Importantly, this means that the sector of the market for treating age-related disorders such as Parkinson's and Alzheimer's disease can only grow.

This report aims to provide an overview of the current situation within the neurodegenerative disease market as well as discussing the status of R&D within this sector. The report considers in depth the major neurodegenerative disease classes such as Alzheimer's disease, dementia and Parkinson's disease, while also touching on Huntington's disease, multiple sclerosis, diabetic neuropathy and amyotrophic lateral sclerosis.

Neurodegenerative disorders are characterised by selective and symmetric loss of neurons in motor, sensory or cognitive systems. Examination of the patterns of cell loss, along with the identification of disease-specific cellular markers, have resulted in a greater accuracy of disease classification. For example, senile plaques, neurofibrillary tangles, neuronal loss and acetylcholine deficiency define Alzheimer's disease; Lewy bodies and depletion of dopamine characterise Parkinson's disease; cellular inclusions and swollen motor axons are found in amyotrophic lateral sclerosis; and g-aminobutyric acid-containing neurons of the neostriatum are lost in Huntington's disease.

Of the major neurodegenerative disorders, Alzheimer's disease currently affects 4 million people in the US. The clinical features of the condition include progressive memory impairment and short-term memory loss. Onset usually occurs between the ages of 40 and 90 years, with a number of varying factors contributing to an individual's risk of developing the disease. Parkinson's disease affects between 500,000 and 1,500,000 people in the US, with 50,000 new cases reported annually. Some 70% of cases are diagnosed as idiopathic Parkinson's disease, where the exact cause is unknown and cannot be attributed to trauma, infection or drug use.

Chapter 1 provides an introduction to neurodegenerative diseases, covering symptoms, diagnostic criteria, disease prevalence, pathology and aetiology. This chapter also briefly discusses the current treatment options for each disease, including both pharmacological and non-pharmacological approaches.

Chapter 2 details the drugs currently on the market for each of the diseases and discusses the most recent clinical trials. There are currently no existing cures for any of the neurodegenerative diseases, with existing treatment options focusing on alleviating the symptoms of the disease. Levodopa, the most successful treatment for Parkinson's disease to date, was first introduced back in the 1970s. Although effective initially, severe side effects develop that are often just as distressing as the symptoms of Parkinson's disease. In contrast, effective treatments for the symptoms of Alzheimer's disease have emerged only relatively recently. However, all of the products currently on the market for Alzheimer's disease share the same mechanism of action, which relies on the manipulation of the very neurotransmitters that are degraded during the course of Alzheimer's disease. Significant unmet needs exist within all sectors of the neurodegenerative market, with one of the greatest needs being the development of disease-modifying treatments.

Chapter 3 discusses the status of R&D within the neurodegenerative market, with the emphasis placed on drugs in the later stages of clinical development. Drugs which are of particular interest have been profiled in depth, while drugs in preclinical development have been summarised in tables.

Chapter 4 discusses the potential of the neurodegenerative market and predicts future sales for key products. It also highlights the factors that will influence the value of the market and discusses the unmet needs and opportunities for expansion within each of the neurodegenerative sectors.

Chapter 5 provides profiles of selected companies that are either actively pursuing R&D within the neurodegenerative sector, or currently market products in this area.

The neurodegenerative market is still in its infancy, despite the Alzheimer's disease sector alone achieving sales of over $1 billion in 1999. The most valuable sector within the neurodegenerative market is the market for multiple sclerosis and amyotrophic lateral sclerosis, which has the potential to reach over $16 billion. It is clear that the neurodegenerative market presents potential for any company willing to invest in R&D that will result in effective, disease-modifying or curative therapies.