[英文調查報告書] 阿茲海默病：2009年市場・產品線藥・機會

Abstract

Overview:

Today' s armoury of approved drugs for the treatment of Alzheimer' s Disease (AD) largely depends on just five therapeutic agents. In 2007, three of these agents represented 88% of global sales, in a market that this report estimates exceeded $6 billion in 2008. There are presently no cures for AD, and current drugs are only able to treat some of the symptoms in some people, with benefits that are often short-lived. Hope is being placed in future disease-modifying drugs, but this report shows that 80% of these candidates are still at Phases I and II. With the relatively recent suspension of two prominent potential disease-modifying Phase III candidates, immediate hopes for these kinds of new-generation drugs now rest on just two to three late-stage candidates. Historically, efforts to develop drugs to treat neurodegenerative disease have demonstrated significant risk, and failure rates have been high. While this has focused companies' efforts on targeting the underlying disease mechanisms, alternative strategies have been stimulated by studies showing that some of the changes found in AD mirror those seen in some other conditions. This report estimates that 30% of current Phase III trials are investigating drugs already approved for other indications. A high proportion of Phase III studies are also investigating new formulations of existing approved drugs or new drug combinations. The AD market offers high growth potential, particularly as more effective treatments are developed. It is also evident that therapeutic opportunities in this field are still wide open, as unmet medical need grows. This report gives a comprehensive overview of the market performance of approved AD drugs, globally, regionally and in the US. The current pipeline, drug development strategies and opportunities in this field are also reviewed.

Alzheimer' s Disease:

In 2006 it was estimated that 27 million people globally were suffering from AD - a figure that is expected to quadruple to more than 100 million by 2050, if a cure is not found. Direct and indirect costs of AD and other dementias in the US are more than $148 billion annually, with worldwide costs for dementia care estimated at $315 billion annually. The 2003 World Health Report indicated that dementia contributed 11.2% of years lived with disability in people aged 60 years and older. This is higher than strokes (9.5%), musculoskeletal disorders (8.9%), cardiovascular disease (5.0%) and all forms of cancer (2.4%).

Markets:

The global AD drug market has grown steadily over the last decade, from around $500 million in 1999 to over $6 billion in 2008, which is an average increase of more than 33% per year. In the last five years, the average growth rate was 23%. Just five approved drugs dominate global sales, three of which represented 88% of global sales in 2007.

Pipeline:

In contrast to the handful of approved drugs for the treatment of AD - where just five agents account for an estimated 95%+ of drug sales - there are more than 178 candidate drugs or candidate treatments currently in the clinical pipeline. Of these, 82% are at Phases I and II. In addition to drugs aimed at targeting AD directly, more than 35 other drug classes are being investigated in an effort to development other strategies for treating AD and its symptoms.

Questions answered in this report:

Which AD drugs are the market leaders? How are the trends in the sales of AD drugs developing on a global and regional basis? What are the sales of individual AD drugs on a global and (where available) regional basis? What are the growth rates and global sales of AD Drugs? What are the forward projections of market growth in the AD field? What strategies are companies taking in the development of new AD drugs? What are the technical and commercial drivers for drug development in the AD field? What types of potential disease-modifying drugs are being developed to target AD, and where are they in the development pipeline? What therapeutic classes are being investigated in an effort to identify `new-use' applications or repurposing opportunities? What drugs classes are currently in the AD development pipeline? What opportunities are available in the AD therapeutics field? See Content of Report

1. Alzheimer' s Disease

1.1 Alzheimer' s Disease
1.2 Statistics and Costs
1.3 Histopathology
1.4 Amyloid Beta (Aβ)
1.5 Tau Proteins and Neurofibrillary Tangles
1.6 Cholinergic Hypothesis
1.7 Diagnosis
1.8 Cognitive Tests
1.9 Treatment

2. Alzheimer' s Disease Statistics

2.1 Background
2.2 Dementia - Global Population
2.3 Global Incidence
2.4 Global New Cases
2.5 Global Prevalence
2.6 Estimated Global Prevalence in 2020
2.7 Developed and Developing Countries
2.8 Global Trends
2.9 Dementia and AD
2.10 John Hopkins University Study
2.11 Disease Costs

3. The Global Drug Market

3.1 The Global Drug Market

4. Donepezil Hydrochloride (AriceptR)

4.1 Donepezil hydrochloride (AriceptR)
4.2 Global Sales
4.3 Global Sales - Eisai
4.4 Japan Sales - Eisai
4.5 US Sales - Eisai
4.6 Regional Sales - Eisai
4.7 Global Sales - Pfizer

5. Memantine AxuraR NamendaR EbixaR

5.1 Memantine

6. Rivastigmine Tartrate (ExelonR)

6.1 Rivastigmine Tartrate

7. Piracetam NootropilR

7.1 Piracetam

8. Galantamine (RazadyneR)

8.1 Galantamine Hydrobromide

9. Global and Regional Sales

9.1 Overview

10. Other Marketed Therapeutic Agents

10.1 Background
10.2 Colostrinin
10.3 Cerebrolysin
10.4 Nicergoline

11. Drug Repurposing in Alzheimer' s Disease

11.1 Background

12. Drug Pipeline - Phases I-III

12.1 Background
12.2 Phase III
12.3 Phase II
12.4 Phase I

13. Discussion

13.1 Overview
13.2 Markets
13.3 Drug Pipeline
13.4 Conclusions

References

Figures

Figure 1.1 Diagram indicating the two cleavage positions of APP (by β- and γ-secretases), generating Aβ
Figure 2.1 The global population (millions) of individuals e" 60.
Figure 2.2 The global incidence of dementia (Number of Individuals/1000) in 2001.
Figure 2.3 Global new cases of dementia (Number of Individuals/1000) in 2001.
Figure 2.4 The global prevalence of dementia in 2001
Figure 2.5 The estimated prevalence of dementia in 2020
Figure 2.6 The estimated prevalence of dementia in 2040
Figure 2.7 The prevalence of dementia in developed and developing countries in 2001 and estimates of prevalence in 2020 and 2040.
Figure 2.8 Estimate of changes (% change) in the prevalence of dementia between 2001 and 2020.
Figure 2.9 Estimate of changes (% change) in the prevalence of dementia between 2001 and 2040.
Figure 3.1. The global sales (US$, millions) of AD drugs from 1999-2008. These figures reflect the sales of the five major anti-AD drugs namely donepezil (AriceptR, Eisai), memantine (AxuraR/NamendaR/EbixaR,Merz), rivastigmine (ExelonR, Novartis), galantamine (RazadyneR, J&J) and piracetam (NootropilR,UCB). Sales in 2008 of the drugs donepezil and memantine were estimated, based on a 10% increase in their respective 2007 sales figures.
Figure 3.2. The annual change (%) in the global sales of anti-Alzheimer' s disease drugs from 1999-2008. These figures reflect the sales of the five major anti-Alzheimer' s disease drugs namely donepezil (AriceptR, Eisai), memantine (AxuraR/NamendaR/EbixaR,Merz), rivastigmine (ExelonR, Novartis), galantamine (RazadyneR, J&J) and piracetam (NootropilR,UCB). Sales in 2008 of the drugs donepezil and memantine were estimated, based on a 10% increase in their global 2007 sales figures.
Figure 3.3 The global sales histogram (US$, Millions) for 2008 of the anti-Alzheimer' s disease donepezil (AriceptR, Eisai), memantine (AxuraR/NamendaR/EbixaR,Merz), rivastigmine (ExelonR, Novartis), galantamine (RazadyneR, J&J) and piracetam (NootropilR,UCB). Sales for 2008 for the drugs donepezil and memantine were estimated, based on a 10% increase in Eisai and Merz global 2007 sales figures.
Figure 3.4 The global sales pie chart (US$, Millions) for 2008 of the anti-Alzheimer' s disease drugs donepezil (AriceptR, Eisai), memantine (AxuraR/NamendaR/EbixaR,Merz), rivastigmine (ExelonR, Novartis), galantamine (RazadyneR, J&J) and piracetam (NootropilR,UCB). Sales for 2008 for the drugs donepezil and memantine were estimated, based on a 10% increase in Eisai and Merz global 2007 sales figures.
Figure 3.5 The global sales histogram (US$, Millions) for 2007 of the anti-Alzheimer' s disease drugs donepezil (AriceptR, Eisai), memantine (AxuraR/NamendaR/EbixaR,Merz), rivastigmine (ExelonR, Novartis), galantamine (RazadyneR, J&J) and piracetam (NootropilR,UCB).
Figure 3.6 The global sales pie chart (US$, Millions) for 2007 of the anti-Alzheimer' s disease drugs donepezil (AriceptR, Eisai), memantine (AxuraR/NamendaR/EbixaR,Merz), rivastigmine (ExelonR, Novartis), galantamine (RazadyneR, J&J) and piracetam (NootropilR,UCB).
Figure 4.1 Global sales (US$, millions) of AriceptR (donepezil hydrochloride) by Eisai and Pfizer (under licence to Eisai) from 1999 to 2008. Eisai' s own sales for 2008 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase of the company' s global 2007 AriceptR sales figures.
Figure 4.2 The annual growth (as % change) in the global sales of AriceptR (donepezil hydrochloride) by Eisai and Pfizer (under licence to Eisai) from 1999 to 2008. Eisai' s own sales for 2008 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase of the company' s global 2007 AriceptR sales figures.
Figure 4.3 Global sales (US$, millions) of AriceptR (donepezil hydrochloride) by Eisai from 1999 to 2008. Sales for 2008 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase in their global 2007 AriceptR sales figures.
Figure 4.4 The annual change (as % change) in the global sales of AriceptR (donepezil hydrochloride) by Eisai from 1999 to 2008. Sales for 2008 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase in their global 2007 AriceptR sales figures.
Figure 4.5 Sales (US$, millions) of AriceptR (donepezil hydrochloride) in Japan by Eisai from 1999 to 2008. Sales for 2008 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase Eisai' s/Pfizer' s global 2007 AriceptR sales figures.
Figure 4.6 The annual change (as % change) in the sales of AriceptR (donepezil hydrochloride) in Japan by Eisai from 1999 to 2008. Sales for 2008 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase Eisai' s/Pfizer' s global 2007 AriceptR sales figures.
Figure 4.7 US Sales (US$, millions) of AriceptR (donepezil hydrochloride) by Eisai from 1999 to 2008. Sales for 2008 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase in their 2007 AriceptR sales figures.
Figure 4.8 The annual change (as % change) in the sales of AriceptR (donepezil hydrochloride) in the US by Eisai from 2003 to 2008. Sales for 2008 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase in their 2007 AriceptR sales figures.
Figure 4.9 Global and regional sales (US$, millions) of AriceptR (donepezil hydrochloride) by Eisai from 2002 to 2008. Sales for 2008 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase in their 2007 AriceptR sales figures.
Figure 4.10 2007 relative direct sales (US$, millions) of AriceptR by Eisai in the US, Japan, Europe and Asia (excluding Japan).
Figure 4.11 The annual global change in the sales of AriceptR (donepezil hydrochloride) by Pfizer from 2003 to 2008. Source: Biopharm Reports.
Figure 4.12 The annual change (as % change) in the sales of AriceptR (donepezil hydrochloride) in the Pfizer from 2004 to 2008.
Figure 5.1 Global sales (US$, millions) of AxuraR NamendaR EbixaR (memantine) by Merz and licensees from 2003/4 to 2007/8. Sales for 2008/9 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase Merz' and its licensees 2007 sales figures.
Figure 5.2 The annual change (as % change) in the global sales of AxuraR NamendaR EbixaR (memantine) by Merz and its licensees from 2004/5 to 2008/9. Sales for 2008/9 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase in Merz' 2007 sales figures.
Figure 5.3 Annual US sales (US$, millions) of AxuraR NamendaR EbixaR (memantine) by Merz and licensees from 2003/4 to 2007/8. Sales for 2008/9 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase Merz' and its licensees 2007 sales figures.
Figure 5.4 The annual change (as % change) in the US sales of AxuraR NamendaR EbixaR (memantine) by Merz and its licensees from 2004/5 to 2008/9. Sales for 2008/9 for the drugs were not available at the time of publication of this reports and have been estimated based on a 10% increase in Merz' 2007 sales figures.
Figure 5.5 Regional sales (US$, millions) of AxuraR NamendaR EbixaR (memantine) by Merz and licensees from 2003/4 to 2006/7.
Figure 6.1 Global sales (US$, millions) of ExelonR (rivastigmine tartrate) by Novartis from 2000 to 2008.
Figure 6.2 The annual change in the global sales of ExelonR by Novartis from 2001 to 2008.
Figure 6.3 US sales (US$, millions) of ExelonR (rivastigmine tartrate) by Novartis from 2001 to 2008.
Figure 6.4 The annual change in the US sales of ExelonR by Novartis from 2002 to 2008.
Figure 7.1. The global sales (US$, millions) of NootropilR (piracetam) by UCB from 2000 to 2008
Figure 7.2 The annual change (as % change) in the global sales of NootropilR by BMS from 2001 to 2008.
Figure 7.3. The sales (US$, millions) of NootropilR (piracetam) by UCB from 2005 to 2008 (Europe and Worldwide)
Figure 9.1 US sales of donepezil, memantine, Rivastigmine and galantamine in 2007.
Figure 9.2 US sales of donepezil, memantine, rivastigmine and galantamine in 2008.
Figure 9.3 US sales of AD drugs from 2001 - 2008. Sales of Eisai' s Aricept in 2008
have been estimated based on a 10% increase on the company' s sales figures of 2007.
Figure 9.4 US sales of AD drugs from 2004 - 2008, as % Change. Sales of Eisai' s Aricept in 2008 have been estimated based on a 10% increase on the company' s sales figures of 2007.
Figure 12.1. Alzheimer' s disease - drug candidates in the development pipeline, Phase I - III
Figure 12.2 Phase III Alzheimer' s disease drug categories. SA: Single Agent (a single candidate molecule that has not been approved other indications). SOAD: Single Other Approved Drug (a single drug that has already been approved for another indication). Nutr Suppl: Nutritional Supplement MOAD: Multiple Other Approved Drugs (multiple drugs that have already been approved for other indication).
Figure 12.3 Phase III Alzheimer' s disease drug categories. SA: Single Agent (a single candidate molecule that has not been approved other indications). SOAD: Single Other Approved Drug (a single drug that has already been approved for another indication). Nutr Suppl: Nutritional Supplement MOAD: Multiple Other Approved Drugs (multiple drugs that have already been approved for other indication).
Figure 12.4 Phase II Alzheimer' s disease drug categories. SA: Single Agent single candidate molecule that has not been approved other indications). SOAD: Single Other Approved Drug (a single drug that has already been approved for another indication). Nutr Suppl: Nutritional Supplement MOAD: Multiple Other Approved Drugs (multiple drugs that have already been approved for other indication).
Figure 12.5 Phase II Alzheimer' s disease drug categories. SA: Single Agent single candidate molecule that has not been approved other indications). SOAD: Single Other Approved Drug (a single drug that has already been approved for another indication). Nutr Suppl: Nutritional Supplement MOAD: Multiple Other Approved Drugs (multiple drugs that have already been approved for other indication).
Figure 12.6 Phase I Alzheimer' s disease drug categories. SA: Single Agent single candidate molecule that has not been approved other indications). SOAD: Single Other Approved Drug (a single drug that has already been approved for another indication). Nutr Suppl: Nutritional Supplement MOAD: Multiple Other Approved Drugs (multiple drugs that have already been approved for other indication).
Figure 12.7 Phase I Alzheimer' s disease drug categories. SA: Single Agent single candidate molecule that has not been approved other indications). SOAD: Single Other Approved Drug (a single drug that has already been approved for another indication). Nutr Suppl: Nutritional Supplement MOAD: Multiple Other Approved Drugs (multiple drugs that have already been approved for other indication).
Figure 13.1. The global sales of AD drugs from 1999-2008. These figures reflect the sales of the five major anti-Alzheimer' s disease drugs namely donepezil (AriceptR, Eisai), memantine (AxuraR/NamendaR/EbixaR,Merz), rivastigmine (ExelonR, Novartis), galantamine (RazadyneR, J&J) and piracetam (NootropilR,UCB). Sales in 2008 of the drugs donepezil and memantine were estimated, based on a 10% increase in Eisai' s and Merz' global 2007 sales figures.
Figure 13.2. The annual change in the global sales of anti-Alzheimer' s disease drugs from 1999-2008. These figures reflect the sales of the five major anti-Alzheimer' s disease drugs namely donepezil (AriceptR, Eisai), memantine (AxuraR/NamendaR/EbixaR,Merz), rivastigmine (ExelonR, Novartis), galantamine (RazadyneR, J&J) and piracetam (NootropilR,UCB). Sales in 2008 of the drugs donepezil and memantine were estimated, based on a 10% increase in Eisai' s and Merz' global 2007 sales figures.
Figure 13.3 The global sales histogram (US$, Millions) for 2008 of the anti-Alzheimer' s disease donepezil (AriceptR, Eisai), memantine (AxuraR/NamendaR/EbixaR,Merz), rivastigmine (ExelonR, Novartis), galantamine (RazadyneR, J&J) and piracetam (NootropilR,UCB).
Figure 13.4. Alzheimer' s disease - drug candidates in the development pipeline, Phase I - 3

Tables

Table 3.1 The global sales (US$, millions) 2004-2008 of the anti-Alzheimer' s drugs donepezil (AriceptR, Eisai), memantine (AxuraR/NamendaR/EbixaR,Merz), rivastigmine (ExelonR, Novartis), galantamine (RazadyneR, J&J) and piracetam (NootropilR,UCB) and colostrinin (colostrinin"!, Regen Therapeutics). * Sales for 2008 for the drugs donepezil and memantine were estimated, based on a 10% increase in Eisai and Merz global 2007 sales figures.
Table 9.1 Global and regional sales of the AD drugs donepezil, memantine, rivastigmine, Piracetam, galantamine and colostrinin. *= Sales by Eisai **= sales by Pfizer
Table 11.1 Number of drug drugs studies relating to potential repurposing and others which may treat some of symptoms of AD
Table 11.2a Phase III studies relating to potential repurposing and others linked to the treatment of some of the symptoms of AD
Table 12.2 Phase II Alzheimer' s disease drug categories. SA: Single Agent (a single candidate molecule that has not been approved other indications). SOAD: Single Other Approved Drug (a single drug that has already been approved for another indication). Nutr Suppl: Nutritional Supplement MOAD: Multiple Other Approved Drugs (multiple drugs that have already been approved for other indication).
Table 12.3 Phase I Alzheimer' s disease drug categories. SA: Single Agent (a single candidate molecule that has not been approved other indications). SOAD: Single Other Approved Drug (a single drug that has already been approved for another indication). Nutr Suppl: Nutritional Supplement MOAD: Multiple Other Approved Drugs (multiple drugs that have already been approved for other indication).
Table 13.1 Phase III Alzheimer' s disease drug categories. SA: Single Agent (a single candidate molecule that has not been approved other indications). SOAD: Single Other Approved Drug (a single drug that has already been approved for another indication). Nutr Suppl: Nutritional Supplement MOAD: Multiple Other Approved Drugs (multiple drugs that have already been approved for other indication).

阿茲海默病：2009年市場・產品線藥・機會

Alzheimer's Disease: Markets, Pipeline and Opportunities 2009