Traumatic Brain Injury: Therapeutic and Diagnostic Pipeline Assessment and Commercial Prospects
Traumatic brain injury (TBI) is the single leading cause of death and disability worldwide in children and young adults following an injury. With around 10 million new cases diagnosed and 1.5 million deaths occurring per annum globally; this ‘silent’ epidemic accounts for more fatalities than diabetes or lung cancer.
Publication Date: October 21, 2014
Pricing:
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Despite three decades of intensive research and development effort, translating benchside to bedside success remains the single greatest challenge in TBI. All 33 Phase III TBI clinical trials testing the efficacy of neuroprotective agents have failed over the past 20 years. Consequently, no FDA-approved TBI therapy exists.
Nevertheless, 2013 witnessed the creation of a National Research Action Plan (NRAP) to address the current unmet needs in TBI. Point-of-care (POC) diagnostic devices look set to revolutionize the diagnosis of TBI. By year end 2014, a number of POC diagnostic devices may be approved by the FDA.
Key Features:
♦ Identification of the major challenges within TBI R&D including unmet needs, clinical trial design and alternative R&D approaches, the potential of biomarkers, regulatory hurdles and ethical issues
♦ Clinical and commercial analysis of key Phase III TBI drug candidates and point-of-care diagnostic devices
♦ An assessment of the potential financial TBI market, with seven major market forecasts to 2020 for key pipeline drug candidates and point-of-care diagnostic devices
Purchase of this report will enable you to:
♦ Assess opportunities and challenges influencing strategic TBI R&D
♦ Identify key TBI drug candidates and point- of-care diagnostic devices in late-phase development based on sales forecasts to 2020
♦ Gain an impartial perspective of strategies that can be used to enhance commercial success
Key questions answered:
♦ What are the major unmet needs in the treatment of TBI?
♦ What are the leading potential TBI biomarkers?
♦ Who are the key specialist players involved in the TBI market and what business models are they using to raise company performance?
♦ What lessons can investors learn from failed TBI drug candidates?
♦ How can companies optimize strategic TBI R&D to maximize commercial success?
♦ What are the key leading drug candidates in the TBI pipeline?
♦ What are the key leading point-of-care diagnostic devices in the TBI pipeline?
♦ What are the anticipated revenues for key pipeline drug candidates?
♦ What are the anticipated revenues for key pipeline point-of-care diagnostic devices?
Table of Contents
1 EXECUTIVE SUMMARY
1.1 Scope of Traumatic Brain Injury Research and Development Highlights 2014
1.2 Methodology
1.3 Traumatic Brain Injury is the Leading Cause of Death and Disability Following an Injury
1.4 Supportive Management Forms the Cornerstone of TBI Treatment
1.5 Failure of Over 30 Phase III Trials Presents Major Research and Development (R&D) Challenges in TBI
1.6 There are Numerous Unmet Needs in TBI
1.7 The Late-Stage Therapeutic TBI Pipeline is Limited
1.8 Emerging TBI Diagnostic Products
1.9 Financial Analysis of the Potential TBI Market
2 TRAUMATIC BRAIN INJURY: DISEASE BACKGROUND
2.1 An Introduction to Traumatic Brain Injury
2.2 There is No Clear, Concise Definition of TBI
2.3 TBI is a Complex Disorder with a Range of Typologies
2.3.1 Primary TBI
2.3.2 Secondary TBI
2.3.3 Focal TBI
2.3.4 Diffuse TBI
2.3.5 Open TBI
2.3.6 Closed TBI
2.4 Falls are the Leading Cause of TBI
2.5 Specific Symptoms are Indicative of TBI
2.6 Two Pathological Stages are Involved in TBI
2.7 There is No Gold-Standard TBI Diagnostic Test
2.7.1 Glasgow Coma Score
2.7.2 Rancho Los Amigos Scale
2.7.3 Westmead Post Traumatic Amnesia (PTA) Scale
2.8 The Staging of TBI is Dependent Upon Brain Injury Severity
2.8.1 Mild TBI
2.8.2 Moderate TBI
2.8.3 Severe TBI
2.8.4 The Majority of the TBI Patient Population Sustain Mild Brain Injuries
2.9 Predicting the Prognosis of TBI is Difficult
2.9.1 Glasgow Outcome Scale
2.9.2 Disability Rating Scale
2.9.3 The NIH’s International Mission for Prognosis and Clinical Trial (IMPACT) Prognosis Model
2.9.4 The MRC’s Corticosteroid Randomization After Significant Head Injury (CRASH) Prognosis Model
2.10 The Prognosis of Severe TBI is Particularly Poor
2.10.1 Numerous Complications are Associated with TBI
3 THE EPIDEMIOLOGY AND FINANCIAL IMPLICATIONS OF TBI
3.1 Epidemiology of TBI in the Seven Major Markets
3.1.1 Road Traffic Accidents Set To Become the Third Leading Cause of Global Disease and Disability
3.1.2 The incidence of Combat –Related TBI is Rising
3.2 The Financial Impact of TBI is High
4 THE CURRENT MANAGEMENT OF TBI
4.1 The Management of TBI
4.2 Acute Complications of Mild TBI are a Priority Concern
4.3 The Management of Moderate and Severe TBI Attempts to Minimize Secondary Injury
4.4 Pharmacological Treatment Forms the Cornerstone of Post TBI Complications
4.5 TBI Rehabilitation Involves a Multi Therapy Approach
5 THE MAJOR CHALLENGES OF TBI RESEARCH AND DEVELOPMENT (R&D)
5.1 Failure of Over 30 TBI Phase III Clinical Trials of Neuroprotectives in the Past 20 Years
5.2 The Vision of TBI Research
5.3 Obama's National Research Action Plan
5.4 TBI Clinical Trial Challenges
5.4.1 Heterogeneity of the TBI Population
5.4.2 Clinical Trial Design
5.4.3 International Mission on Prognosis and Clinical Trials in TBI (IMPACT) Recommendations
5.5 Alternative Approaches to TBI Research
5.5.1 Systems Biology Research in TBI
5.5.2 Comparative Effectiveness Research in TBI
5.6 The Potential of TBI Biomarkers to Aid R&D
5.6.1 Proteomics-Based Biomarker Discovery in TBI
5.6.2 TBI Diagnostic and Patient Monitoring Platform Development
5.6.3 The Potential of Theranostics in TBI R&D
5.7 TBI Regulatory Issues
5.8 TBI Ethical Challenges
6 UNMET NEEDS IN THE TBI MARKET
6.1 Lack of a Universally Accepted Definition of TBI
6.2 Lack of a Gold-Standard TBI Diagnostic Test
6.3 Under Diagnosis of Mild TBI
6.4 Management of TBI is Not Standardized
6.5 No Approved TBI Treatment is Available
6.6 Elderly TBI Patients are Underserved
6.7 Lack of Big Pharma/Biotech Investment in the TBI Arena
6.8 International TBI Collaborations and Alliances are Required
7 TBI THERAPEUTIC PIPELINE ANALYSIS
7.1 Introduction to the TBI Therapeutics Pipeline
7.2 BHR Pharma’S BHR-100 (Progesterone)
7.2.1 BHR-100’s SyNAPSe Trial
7.3 Teva Pharmaceuticals/Cephalon's Nuvigil (Armodafinil)
7.3.1 Nuvigil’s Phase II Trial Results
7.4 Key Neurotek Pharmaceuticals' KN38-7271
7.5 Neuren Pharmaceuticals’ NNZ-2566
7.5.1 NNZ-2566’s Intrepid- 2566 Trial
7.5.2 NNZ-2566 Oral Formulation Trials
7.6 NNZ-2566’S Commercialization Potential
7.7 Neurohealing Pharmaceuticals' NH001 (Apomorphine)
7.8 Neurovive Pharmaceuticals' NEUROSTAT (Ciclosporin-A)
7.8.1 NeuroSTAT’s Clinical Trials
7.8.2 NeuroSTAT’s Commercialization Potential
7.9 Oxygen Biotherapeutics' Oxycyte (Perflurocarbon Oxygen Carrier)
7.10 Vasopharm's VAS203
7.10.1 VAS203’s Nostra Trial Results
7.11 Remedy Pharmaceuticals’ RP-1127
7.11.1 RP-1127 Clinical Trials
7.11.2 RP-1127 Commercialization Potential
8 OVERVIEW OF KEY ACADEMIC AND GOVERNMENTAL TBI RESEARCH
8.1 Introduction to Academia and Governmental TBI Research
8.2 Review of Leading TBI Pipeline Drug Classes
8.2.1 Acetylcholinesterase Inhibitors
8.2.2 Erythropoietin
8.2.3 Growth Hormone
8.2.4 Stem Cells
8.3 Academic Research for the Discovery of New TBI Drug Targets
8.3.1 5-Lipoxgenase Activating Proteins (FLAP) Inhibitors
8.3.2 Purinergic Receptor Antagonists
8.3.3 Proinflammatory Cytokine Inhibitors
8.3.4 Cysteine Protease Inhibitors
8.3.5 Transcranial Delivery of Glutathione Used in Innovative Dynamic Imaging Study of Mild TBI
8.3.6 Membrane Attack Complex (MAC) of the Terminal Complemental Pathway
8.4 US Governmental Agency Research for the Discovery of New TBI Drug Targets
8.4.1 US Department of Veterans Affairs
8.4.2 US Department of Defense
8.4.3 National Institute of Neurological Disorders and Stroke
9 POTENTIAL TBI BIOMARKERS
9.1 Introduction to Potential TBI Biomarkers
9.2 S100 Β Caclcium Binding Protein
9.3 Neuron Specific Enolase (NSE)
9.4 Glial Fibrillary Acidic Protein (GFAP)
9.5 Neurofilament Light Protein (NFL)
9.6 Spectrin Breakdown Products
9.7 Beta-Amyloid Protein (AΒ)
9.8 Myelin Basic Protein (MBP)
9.9 Ubiquitin Carboxyl-Terminal Hydrolase Isoenzyme L1 (UCH-L1)
9.10 Tau Proteins
9.11 Ampar Peptide/GLUR1
9.12 TBI Biomarker Assay Services
9.12.1 Grace Laboratories
9.12.2 Banyan Biomarkers
10 TBI POINT OF CARE DIAGNOSTIC DEVICES PIPELINE ANALYSIS
10.1 Introduction to the TBI Point of Care Diagnositc Devices Pipeline
10.2 Luoxis Diagnostics/Ampio Pharmaceuticals' Redoxsys Diagnostic System
10.2.1 RedoxSYS Diagnostic System’s Phase III Isolated TBI Trial Results
10.2.2 RedoxSYS Diagnostic System’s Commercialization Potential
10.3 Banyan Biomarkers' UCH-L1/GFAP Detection Assay
10.3.1 UCH-L1/GFAP Detection Assay Commercialization Potential
10.4 Biodirections' Tbit Test Platform
10.4.1 Tbit Test Platform’s Commercialization Potential
10.5 SFC Fluidics' TBI Diagnostic Platforms
10.5.1 SFC Fluidics’ TBI Diagnostic Platforms Commercialization Potential
10.6 Brainscope's Ahead M-100
10.6.1 Ahead M-100’s Clinical Trial Results
10.6.2 Ahead M-100 Commercialization Potential
10.7 Cerora's Mindreader Biosensor Biomarker Program
10.7.1 Mindreader’s Commercialization Potential
10.8 ELMindA's BNA Platform
10.8.1 BNA Platform’s Commercialization Potential
10.9 Neuro Assessment Systems' Neuro-Screen
10.9.1 Neuro-Screen’s Commercialization Potential
11 FINANCIAL FORECAST OF THE POTENTIAL TBI MARKET
11.1 Arrowhead's Analysis of the Potential Therapeutic TBI Market
11.2 Analysis of the Potential TBI POC Diagnostic Devices Market
11.3 SWOT Analysis of the Potential TBI Market
11.4 Summary of the Potential TBI Market
12 COMPANY BRIEFS
12.1 Banayan Biomarkers Inc.
12.2 BHR Pharma LLC
12.3 Biodirection Inc.
12.4 Brainscope Company Inc.
12.5 Cerora Inc.
12.6 ElMindA Ltd.
12.7 Grace Laboratories LLC
12.8 KeyNeurotek Pharmaceuticals AG
12.9 Luoxis Diagnostics
12.10 Neuro Assessment Systems
12.11 Neurohealing Pharmaceuticals
12.12 Neuren Pharmaceuticals Ltd.
12.13 Neurovive Pharmaceuticals AB
12.14 Oxygen Biotherapeutics Inc.
12.15 Phlogistix LLC
12.16 Remedy Pharmaceuticals Inc.
12.17 SFC Fluidics LLC
12.18 TEVA Pharmaceutical Industries Ltd.
12.19 Vasopharm
13 BIBLIOGRAPHY
List of Tables
Table 1: TBI Incidence Forecast in 2014 and 2020 in the Seven Major Markets
Table 2: TBI Pipeline Candidates Undergoing Late-Stage Clinical Development by Pharma/Biotech Companies
Table 3: Late-stage TBI POC Diagnostic Devices Pipeline, Jan 2014
Table 4: Financial Forecast of the Potential TBI Market, in 2014 and 2020 in the US and EU ($ billions)
Table 5: The Glasgow Coma Score
Table 6: The Ranchos Los Amigos Scale
Table 7: Summary of TBI Severity Stratification
Table 8: The Glasgow Outcome Scale
Table 9: The Disability Rating Scale
Table 10: The Disability Rating Scale Prognosis Outcome
Table 11: Complications Associated with TBI
Table 12: Crude Incidence Rate of TBI (per 100,000) in the Seven Major Markets, 2014
Table 13: TBI Incidence Forecast in the Seven Major Markets, 2014-2020
Table 14: Mild TBI Incidence Forecast in the Seven Major Markets, 2014-2020
Table 15: Moderate TBI Incidence Forecast in the Seven Major Markets, 2014-2020
Table 16: Severe TBI Incidence Forecast in the Seven Major Markets, 2014-2020
Table 17: Brain Trauma Foundation Guidelines for the Acute Management of Severe TBI
Table 18: Management of Common Post-TBI Complications
Table 19: Failed Phase III Clinical Trials of Novel Neuroprotectives in Moderate and Severe TBI over the Past 30 Years
Table 20: National Research Action Plan Deadline Targets in TBI
Table 21: IMPACT Recommendations for the Use of Common Outcome Measures in TBI
Table 22: Applications of TBI Diagnostic and Patient Monitoring Platforms
Table 23: Incentives Granted to Orphan Drug Developers
Table 24: TBI Therapeutic Pipeline, Jan 2014
Table 25: Comparison of ProTECT II and Xiao Clinical Trials
Table 26: Comparison of SyNAPSe and ProTECT III Clinical Trials
Table 27: TBI Point- of-Care Diagnostic Devices Pipeline, Jan 2014
Table 28: Arrowhead’s Financial Forecast of the Potential Therapeutic TBI Market in the US and EU, 2014-2020 ($ millions)
Table 29: Arrowhead’s Financial Forecast of the Potential TBI POC Diagnostic Devices Market in the US and EU, 2014-2020 ($ millions)
Table 30: Arrowhead’s Financial Forecast of the Potential TBI Market in the US and EU, 2014-2020 ($ billions)
List of Figures
Figure 1: TBI Incidence Forecast in 2014 and 2020 in the Seven Major Markets
Figure 2: Major Unmet Needs in TBI
Figure 3: Finanical Forecast of the Potential TBI Market, in 2014 and 2020 in the US and EU ($ billions)
Figure 4: The Anatomy of the Human Brain
Figure 5: Cause of all TBIs within the US General Population, 2010
Figure 6: The Pathophysiological Pathways Involved in Secondary Brain Injury
Figure 7: TBI Patient Population by Brain Injury Severity
Figure 8: TBI Incidence Forecast in the Seven Major Markets, 2014-2020
Figure 9: Mild TBI Incidence Forecast in the Seven Major Markets, 2014-2020
Figure 10: Moderate TBI Incidence Forecast in the Seven Major Markets, 2014-2020
Figure 11: Severe TBI Incidence Forecast in the Seven Major Markets, 2014-2020
Figure 12: Info graphic on Global Road Traffic Accidents
Figure 13: Number of Persons Injured in a Road Traffic Accident within the US, 2000-2011
Figure 14: Total Worldwide Number of TBIs Diagnosed in US Military Personnel, 2000-2012
Figure 15: The Total Worldwide Number of Combat-Related TBIs Diagnosed in US Military Personnel, 2000-2012
Figure 16: Management Algorithm of TBI According to Glasgow Coma Score
Figure 17: NRAP’s Approach to Address the Current Unmet Needs in TBI R&D
Figure 18: The Use of Biomarkers to Maximize TBI R&D
Figure 19: Systems Biology-Based Selection of Potential TBI Biomarkers,
Figure 20: Number of Phase III Randomized Controlled Trials in Moderate and Severe TBI per Five –Year Time Period Between1980 to 2005
Figure 21: Potential TBI Biomarkers
Figure 22: Illustrative of BNA Platform’s Brain Network Activation Patterns
Figure 23: Arrowhead’s Financial Forecast of the Potential Therapeutic TBI Market in the US and EU, 2014-2020 ($ millions)
Figure 24: Arrowhead’s Financial Forecast of the Potential TBI Therapeutics Market in the US and EU, 2014-2020 ($ millions)
Figure 25: SWOT Analysis of the TBI Market, 2014
Figure 26: Arrowhead’s Financial Forecast of the Potential TBI Market in the US and EU, 2014-2020 ($ billions)