Report: Stakeholder Opinions: Diagnostics in Neurology - Predictive biomarkers expand drug revenues TOC

ABOUT DATAMONITOR HEALTHCARE
- About the CNS pharmaceutical analysis team
CHAPTER 1 EXECUTIVE SUMMARY
- Scope of the analysis
- Contributing experts
- Datamonitor insight into diagnostics in neurology
- Related reports
CHAPTER 2 BACKGROUND
- What is a diagnostic test?
  - Biomarkers - objective measures
- Regulation of diagnostics
  - Imaging
  - In vitro diagnostics
    - European Union
    - United States
- The value of a diagnostic test
  - Technical performance
  - Clinical performance
  - False positives and false negatives
CHAPTER 3 CURRENT DIAGNOSTIC TECHNIQUES AND CHALLENGES
- Neurological conditions - differing disease pathophysiology influences biomarker unmet need
  - Delay to accurate diagnosis is particularly slow in Alzheimer' s disease at present
- Alzheimer' s disease
  - Challenges for Alzheimer' s disease biomarkers
    - Proposed criteria for effective biomarkers in Alzheimer' s disease
  - Current diagnostic criteria
    - DSM-IV-TR
    - NINCDS-ADRDA
    - Recent revising suggestion - aiming for earlier detection
  - Functional tests
    - Mini-Mental Status Exam
    - Ruling out other conditions
  - Pathological diagnosis post-mortem
  - Time to accurate diagnosis of Alzheimer' s disease
- Parkinson' s disease
  - Diagnosis is based on clinician observation of symptoms
    - Primary symptoms used for diagnosis
    - Neurological evaluation of Parkinson' s disease
    - Ruling out disorders that produce parkinsonian symptoms
  - Current imaging techniques used by neurologists
  - Time to accurate diagnosis of Parkinson' s disease
- Multiple sclerosis
  - Current diagnostic technique includes MRI scans
  - Magnetic resonance imaging
    - Clinical signs and MRI might be enough for diagnosis
  - Spinal tap
  - Evoked Potential Tests
  - Differential diagnosis
  - Time to accurate diagnosis of multiple sclerosis
- Epilepsy
  - Patient and family reported signs
  - Electroencephalography
    - Portable EEG
  - Magnetic Resonance Imaging
  - Genetic testing
- Migraine
- Insomnia
  - Basic requirements
    - Optional requirements
  - Clinical history
  - Sleep history
  - Polysomnography
- Huntington' s disease
  - Pre-symptomatic diagnosis, but no disease-modifying treatment
    - Predictive genetic test is available, but use is only moderate
    - Pre-implantation screening is rarely undertaken
- Amyotrophic lateral sclerosis
  - The El Escorial diagnostic criteria
CHAPTER 4 IMPACT OF FUTURE DEVELOPMENTS
- Future disease diagnosis
  - Alzheimer' s disease
    - Future diagnostic algorithm likely to include several biomarkers
  - Parkinson' s disease
    - Disease-modifying drug will stimulate early diagnostics research
  - Multiple sclerosis
    - Comparatively mature diagnostic market with several biomarkers
  - Epilepsy
    - Patient reported events and electroencephalography (EEG) likely to remain the mainstay of diagnosis
  - Migraine and insomnia
  - Amyotrophic lateral sclerosis
- Molecular biomarkers present high value market for diagnostic companies
  - Imaging companies
  - Genetic testing companies
  - In vitro assay companies
- Benefit to pharmaceutical companies is substantial
  - Defined patient population leads to more targeted marketing
  - Earlier treatment results in greater revenues
  - Case studies-quantifying the impact of improved biomarkers on drug sales
    - Huntington' s disease-pre-symptomatic "at risk" population-the lucrative untapped market
    - Alzheimer' s disease-incorporation of patients with mild cognitive impairment
- Benefit to patients is significant
  - Earlier treatment and pre-symptomatic medicine
  - Personalized medicine
  - More sophisticated drug development
- Payers will welcome the clarity biomarkers offer
CHAPTER 5 FUTURE IMAGING TECHNOLOGIES
- Definitions
- Alzheimer' s disease and mild cognitive impairment
  - Structural imaging
  - Radiotracer fluorodeoxyglucose
  - Beta-amyloid proves to be the dominant imaging biomarker
    - Beta-amyloid radioligands using PET scans
    - GE Healthcare' s Pittsburgh Compound-B
    - Other beta-amyloid tracers
  - Acetylcholinesterase
- Parkinson' s disease
  - Radiotracers
    - GE Healthcare' s DaTSCAN
  - Transcranial sonography
- Other neurological diseases
  - Epilepsy
  - Multiple sclerosis
CHAPTER 6 FUTURE IN VITRO DIAGNOSTIC TESTS
- Summary
- Serum- and urine-based biomarkers (including genomics)
  - Alzheimer' s disease and mild cognitive impairment
    - Power3' s NuroPro protein serum biomarkers
    - Proteome Sciences' TMT technology mass spectrometry tool for protein biomarker development
    - Nymox Pharmaceutical' s AlzheimAlert urine test
    - Genetic blood testing-DiaGenic and IMGM Laboratories
    - Pronucleon peptides, fluorescently labeled peptides for amyloid detection-Adlyfe
    - Sulfatide, possible specificity for mild Alzheimer' s disease
    - Genomics, genetic susceptibility of sporadic form is becoming clear-Athena Diagnostics and others
  - Parkinson' s disease
    - Neuromelanin-endogenous pigment identifies Parkinson' s disease
    - Genomics, genetic susceptibility of sporadic form is becoming clear-Athena Diagnostics and others
    - Power 3' s NuroPro
  - Multiple sclerosis
    - Anti-glycan antibodies in early stage patients-Glycominds
    - Plasma markers of the disease and Tysabri side effect-BG Medicine
    - Genomics in multiple sclerosis
  - Amyotrophic lateral sclerosis
    - Genomics of ALS-attention shifts to sporadic form
  - Other neurological diseases
- Cerebrospinal fluid
  - Alzheimer' s disease (AD)
    - Beta-amyloid and tau levels have been extensively studied
    - Isoprostane-8,12-iso-iPF2a-VI
  - Parkinson' s disease
    - Neurofilament heavy-chain' s expose axonal damage
  - Other neurological conditions
    - Amyotrophic lateral sclerosis
    - Multiple sclerosis
BIBLIOGRAPHY
- Journal papers and conference abstracts
- Websites
- Datamonitor reports
APPENDIX
- Contributing experts
- About Datamonitor
  - About Datamonitor Healthcare
- Datamonitor Healthcare' s therapy area capabilities
  - About the Disease analysis team
  - Disclaimer
List of Tables
- Table 1: Comparative biomarker potential across key neurological diseases
- Table 2: DSM-IV criteria for Alzheimer' s disease type dementia
- Table 3: Unified Parkinson' s Disease Rating Scale-cognition, behavior and mood
- Table 4: New multiple sclerosis diagnostic criteria (McDonald criteria)
- Table 5: Prevalence rate of mild cognitive impairment (MCI)
- Table 6: A(1-42 in cerebrospinal fluid
List of Figures
- Figure 1: Typical diagnostic biomarker development process
- Figure 2: Distribution graph of biomarker accuracy
- Figure 3: False positives and false negatives - distribution curve
- Figure 4: Mean time between initial presentation to accurate diagnosis of Alzheimer' s disease, Parkinson' s disease and multiple sclerosis
- Figure 5: Time (months) from presentation to accurate diagnosis of Alzheimer' s disease, 2006
- Figure 6: Percentage of neurologists using each diagnostic imaging technique to make a diagnosis of Parkinson' s disease, 2007
- Figure 7: Time (months) from presentation to accurate diagnosis of Parkinson' s disease, 2007
- Figure 8: Current diagnostic algorithm for multiple sclerosis
- Figure 9: MRI scan image of a multiple sclerosis patients brain, and a normal individual
- Figure 10: Magnetic resonance imaging (MRI) scanner
- Figure 11: Time (months) from presentation to accurate diagnosis of multiple sclerosis (MS), 2006
- Figure 12: An electroencephalograph (EEG)
- Figure 13: Photograph of a portable eletroencephalography (EEG) unit
- Figure 14: Genetic risk of developing Huntington' s disease
- Figure 15: Points of diagnosis of Alzheimer' s disease
- Figure 16: Revenue gain in the Alzheimer' s disease market value with the inclusion of patients with amnestic mild cognitive impairment (amMCI), 2013-17

Stakeholder Opinions: Diagnostics in Neurology - Predictive biomarkers expand drug revenues

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