PharmaFocus: Biomarkers in Alzheimer's Disease -

Published: June 2013 | Pages: 179 

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is characterized by memory loss, cognitive impairment, and functional decline. The disease has emerged as a major global health priority especially because of its rapidly accelerating prevalence worldwide. In order to tackle the AD scourge , there is an urgent need for tools that will allow for the early and accurate diagnosis of AD, as well as the identification of populations at risk. A biomarker is an indicator of biological processes that can be objectively measured and evaluated, and well-validated biomarkers are required to satisfy these needs in AD.
The search for biomarkers that are reflective of the disease process in AD has been and continues to be an active area of research, but has been hampered by a lack of clear understanding of the pathological mechanisms that underlie the disease. Nonetheless, several biomarkers have been developed to date that indicate the presence of AD pathology and AD-associated neuronal injury in vivo. Such biomarkers have the potential for clinical use in etiological determination, predictive prognosis, monitoring disease progression, and in clinical trials of potential disease-modifying therapies for AD.
Key Questions Answered
- What are the main biomarkers in AD? What AD biomarkers are commercially available in the market and which are in pipeline development?
- What are the roles of biomarkers in AD diagnosis and drug discovery?
- What are the major unmet needs with regards to AD biomarkers?
- What are the views of KOLs on the present and future landscape of the AD biomarkers market?
- What is the impact of government regulation on AD biomarker development and market adoption? What governmental and industry changes are likely to influence the use of biomarkers in the near future? 
Key Findings
- Amyloid-based biomarkers, and in particular, amyloid PET ligands, are the furthest developed biomarkers for AD and although they have immense value in diagnosis and drug discovery, there is a remaining need for biomarkers of other pathological processes.
- There is a great need for simple inexpensive biomarker assays that can be implement as diagnostic screens for AD and there are numerous blood-based biomarker assays in pipeline aiming to target this need.
- Government regulation will play a major role in biomarker development, clinical market access and use in drug discovery both in the US and in the EU.
- Overview of Alzheimer's disease, including disease etiology and pathophysiology and how these inform biomarker targets.
- Overview of AD biomarkers, the major classes of biomarkers an the different potential roles of biomarkers in clinical use and drug development.
- Key topics covered include amyloid biomarkers, tau biomarkers, and other molecular biomarkers for AD in development with product profiles for marketed as well as promising pipeline assays. Also discussed are functional and structural imaging biomarkers for AD.
- Analysis of the unmet needs, and opportunities within the AD biomarker arena, as well as drivers and barriers impacting the AD biomarker market.
- Insightful review of the regulatory considerations impacting biomarker development, market access and use in clinical drug development
Key Benefits
- Develop and design your in-licensing and out-licensing strategies through a review of pipeline products and technologies, and by identifying the companies with the most robust pipeline.
- Develop business strategies by understanding the factors shaping and driving AD biomarker development and market adoption.
- Drive revenues by understanding the key trends, innovative products and technologies, and companies likely to impact the AD biomarker market in future.
- Organize your sales and marketing efforts by identifying the market categories and segments that present maximum opportunities for consolidations, investments and strategic partnerships
1.1 List of Tables
1.2 List of Figures
2 Introduction
2.1 Catalyst
3 Alzheimer’s Disease Overview
3.1 Continuum of AD – Preclinical, MCI and AD Dementia
3.1.1 Preclinical AD
3.1.2 MCI
3.1.3 AD Dementia
3.2 Etiology and Pathophysiology
3.2.1 Etiology
3.2.2 Pathophysiology
4 AD Biomarkers – Overview
4.1 What are Biomarkers?
4.2 Criteria for Good Biomarkers
4.2.1 Sensitivity and Specificity of Biomarkers
4.3 Role of Biomarkers in AD Diagnosis
4.3.1 Challenges in Establishing AD Biomarkers as Diagnostic Tools
4.4 Role of Biomarkers in Drug Development
4.5 Biomarker Development and Validation
4.6 Classes of AD Biomarkers by Pathophysiological Mechanism
4.6.1 Temporal Evolution of Biomarkers
5 Unmet Needs Assessment
5.1 Overview
5.2 Unmet Needs Analysis
5.2.1 Patient and Physician Knowledge/Awareness of AD Diagnosis
5.2.2 Generalized Biomarker Unmet Needs
5.2.3 Unmet Need for Diverse Types of Biomarkers
6 AD Biomarkers Market Drivers and Barriers
6.1 Driver: Increasing prevalence of AD corresponding to a growth in the aging population will rapidly expand the biomarker market size
6.2 Driver: Anticipated future cost of biologic AD treatments will drive the use of biomarker diagnostics
6.3 Driver: Favorable regulatory standards for the application of biomarkers in drug discovery
6.4 Barrier: Present lack of disease-modifying treatments hinders the use of diagnostic tests
6.5 Barrier: Rigorous, expensive, and time-consuming nature of biomarker development and validation
6.6 Barrier: Reimbursement restrictions for diagnostic testing
6.7 Barrier: Healthcare system and physician practice barriers limit patient referral to specialists and the use of biomarker tests
7 Amyloid Beta Biomarkers
7.1 Overview of Biomarker Class
7.2 Drug Therapies Targeting Amyloid Beta
7.2.1 Overview
7.2.2 Representative Pipeline Drugs
7.3 Amyloid Biomarker Assays
7.3.1 Amyloid PET-Imaging
7.3.2 CSF-Based Amyloid Assays
7.3.3 Other Amyloid Assays in Development
8 Tau-Related Biomarkers
8.1 Overview of Biomarker Class
8.2 Drug Therapies Targeting Tau
8.2.1 Overview
8.2.2 Representative Products
8.3 Tau Biomarker Assays
8.3.1 CSF-Based Tau Assays
8.3.2 Promising Pipeline Products - Tau PET Imaging Ligands
9 Beyond Amyloid and Tau: Other Molecular AD Biomarkers in Development
9.1 Overview
9.1.1 Neuronal and Synaptic Degeneration
9.1.2 Inflammation and Oxidative Stress
9.2 Promising Pipeline Products
9.2.1 Alzheimer’s CSF 16-Plex Assay (Proteome Sciences)
9.3 Blood-Based Biomarkers
9.3.1 Overview
9.3.2 Promising Pipeline Products
10 Functional Brain Imaging Biomarkers
10.1 Overview of Biomarker Class
10.2 Functional Brain Imaging Assays
10.2.1 FDG-PET
10.2.2 FMRI Biomarkers of AD
11 Structural Brain Imaging Biomarkers
11.1 Overview of Biomarker Class
11.2 Structural Brain Imaging Assays
11.2.1 MRI Hippocampal Volumetry
11.2.2 Other Structural Imaging Biomarkers in Pipeline Development
12 Regulatory Considerations Impacting AD Biomarkers
12.1 Clinical Trial Design in AD Drug Development
12.1.1 Regulatory Agency Recommendations
12.1.2 Key Opinion Leaders on the Use of Biomarkers in Drug Clinical Trials
12.1.3 Mapping the Use of Biomarkers in Key AD Drug Clinical Trials
12.1.4 AD Drug Approval, Population or Stage-Specific Indications, and Off-Label Use
12.2 Reimbursement of Biomarker-Based Testing
12.2.1 Concerns Limiting Reimbursement of Biomarker Testing for AD
12.2.2 Region-Specific Differences in Biomarker Test Reimbursement Policies and Pathways in the US and EU
13 Outlook and Opportunities for AD Biomarkers
13.1 Overview
13.2 Key Players, Partnerships, and Associations
13.2.1 National and International AD Biomarkers Consortia
13.2.2 Private Industry Biomarker Partnerships
13.3 Opportunity Analysis
13.3.1 Opportunity: Biomarkers to Determine Appropriate Use of Treatment
13.3.2 Opportunity: Biomarkers as Populations Screens for Alzheimer’s Disease
13.3.3 Opportunity: Continued Development of Varied Biomarkers of Pathophysiology
14 Appendix
14.1 Bibliography
14.2 Abbreviations
14.3 Research Methodology
14.4 Physicians and Specialists Included in this Study
14.5 About the Authors
14.5.1 Authors
14.5.2 Global Head of Healthcare
14.6 About Us
14.7 Disclaimer 
1.1 List of Tables
Table 1: Biomarker Unmet Needs – Current Level of Attainment
Table 2: AD Biomarkers – Market Drivers and Barriers, 2013
Table 3: AD – Amyloid-Targeting Phase III Pipeline, 2013
Table 4: AD – Amyloid-Targeting Phase II Pipeline, 2013
Table 5: Aß Biomarkers by Stage of Development, 2013
Table 6: SWOT Analysis of Amyloid PET Imaging in AD, 2013
Table 7: Product Profile of Amyvid, 2013
Table 8: SWOT Analysis of Amyvid, 2013
Table 9: Product Profile of [18F] Flutemetamol, 2013
Table 10: SWOT Analysis of [18F] Flutemetamol, 2013
Table 11: Product Profile of [18F] Florbetaben, 2013
Table 12: SWOT Analysis of [18F] Florbetaben, 2013
Table 13: Product Profile of NAV4694, 2013
Table 14: SWOT Analysis of NAV4694, 2013
Table 15: Characteristics of ELISA and xMAP Immunoassay Platforms for the Measurement of CSF Biomarkers in AD
Table 16: SWOT Analysis of CSF-Based Amyloid Tests, 2013
Table 17: Product Profile of INNOTEST ß-Amyloid1-42, 2013
Table 18: SWOT Analysis of INNOTEST ß-Amyloid1-42, 2013
Table 19: Product Profile of INNO-BIA AlzBio3, 2013
Table 20: SWOT Analysis of INNO-BIA AlzBio3, 2013
Table 21: Product Profile of EP-AD Diagnostic CSF Test, 2013
Table 22: SWOT Analysis of EP-AD Diagnostic CSF Test, 2013
Table 23: Product Profile of ABtest, 2013
Table 24: SWOT Analysis of ABtest, 2013
Table 25: Product Profile of SAPPHIRE II Eye Test, 2013
Table 26: SWOT Analysis of SAPPHIRE II Eye Test, 2013
Table 27: AD, Tau-Targeting Therapies, Phase III Pipeline, 2013
Table 28: AD, Tau-Targeting Therapies, Phase II Pipeline, 2013
Table 29: AD, Tau-Targeting Therapies, Phase I Pipeline, 2013
Table 30: Tau Biomarkers by Stage of Development, 2013
Table 31: SWOT Analysis of CSF-based Tau Assays, 2013
Table 32: Product Profile of INNOTEST hTau Ag, 2013
Table 33: SWOT Analysis of INNOTEST hTau Ag, 2013
Table 34: Product Profile of INNOTEST PHOSPHO-TAU(181P), 2013
Table 35: SWOT Analysis of INNOTEST PHOSPHO-TAU(181P), 2013
Table 36: SWOT Analysis of Tau PET Imaging in AD, 2013
Table 37: Potential Biomarkers of AD, 2013
Table 38: Product Profile of Alzheimer’s CSF 16-Plex Assay, 2013
Table 39: SWOT Analysis of Alzheimer’s CSF 16-Plex Assay, 2013
Table 40: Product Profile of AclarusDx, 2013
Table 41: SWOT Analysis of AclarusDx, 2013
Table 42: Product Profile of ADpredict Screening Test, 2013
Table 43: SWOT Analysis of ADpredict Screening Test, 2013
Table 44: Product Profile of Alzheimer’s Plasma 9-Plex Assay, 2013
Table 45: SWOT Analysis of Alzheimer’s Plasma 9-Plex Assay, 2013
Table 46: Product Profile of ADtect, 2013
Table 47: SWOT Analysis of ADtect, 2013
Table 48: Product Profile of MCItect, 2013
Table 49: SWOT Analysis of MCItect, 2013
Table 50: Product Profile of LymPro Test, 2013
Table 51: SWOT Analysis of LymPro Test, 2013
Table 52: Functional Brain Imaging Biomarkers by Stage of Development, 2013
Table 53: SWOT Analysis of FDG- PET Imaging in AD, 2013
Table 54: SWOT Analysis of FMRI Biomarkers in AD, 2013
Table 55: Structural Brain Imaging Biomarkers by Stage of Development, 2013
Table 56: SWOT Analysis of MRI Hippocampal Volumetry, 2013
Table 57: Features of an Early-AD Therapy Clinical Trial, 2013
Table 58: Summary of the FDA Guidance for Drug Development in Early AD, 2013
Table 59: Biomarker Use in Ongoing AD Drug Clinical Trials, 2013 
1.2 List of Figures
Figure 1: The Continuum of Alzheimer’s Disease
Figure 2: Atrophy of the Brain in Alzheimer’s Disease
Figure 3: Key Pathological Features in Alzheimer’s Disease
Figure 4: Non-Amyloidogenic Metabolism of APP
Figure 5: Amyloidogenic Metabolism of APP
Figure 6: Neurofibrillary Tangles
Figure 7: Oxidative Damage due to Free Radicals
Figure 8: Biomarkers in Drug Discovery
Figure 9: AD Biomarker Tests by Pathophysiology
Figure 10: Dynamic Changes in Alzheimer’s Disease Biomarkers