1. Executive Summary
1.1 Orphan Drugs for CNS Diseases: Market Overview
1.2 Report Contents - Chapter Overviews
1.3 Research and Analysis Methods

2. Introduction to Orphan Drugs for CNS Disorders
2.1 Defining Orphan Diseases
2.2 What are the Major Orphan CNS Indications?
2.2.1 Huntington's Disease
2.2.2 Amyotrophic Lateral Sclerosis (ALS)
2.2.3 Myasthenia Gravis
2.2.4 Other Orphan CNS Indications
2.3 Orphan Drug Designation: Providing Incentives to Companies
2.3.1 What Benefits Come with Orphan Drug Designation?
2.4 Demand for Orphan Drugs Gathers Momentum
2.4.1 Development of Orphan Drugs

3. The World Orphan CNS Drugs Market, 2014-2024
3.1 How Large Was the Orphan Drugs Market in 2013?
3.1.1 Huntington's Disease: The Largest Orphan CNS Disease Sector in 2012
3.2 The Orphan CNS Drug Market: Revenue Forecast, 2013-2024
3.2.1 What Will Drive Growth in the Market to 2024?
3.2.2 What Will Restrain the Market From 2014-2024?
3.3 Orphan Drugs in Huntington's Disease
3.3.1 Huntington's Disease: Submarket Forecast, 2013-2024
3.3.1.1 Huge Unmet Need to Drive HD Treatment Market
3.3.1.2 Enactment of New Law in US May Add Growth Impetus
3.4 Orphan Drugs in Amyotrophic Lateral Sclerosis
3.4.1 Amyotrophic Lateral Sclerosis: Submarket Forecast, 2013-2024
3.4.1.1 New Drug Launches Will Provide Market Recovery Following Patent Expiry of Rilutek
3.5 Orphan Drugs in Myasthenic Gravis
3.5.1 Myasthenia Gravis: Submarket Forecast, 2013-2024
3.5.1.1 Clinical R&D into New Treatments Keep Patients Hopeful

4. Leading National Markets for Rare CNS Indications 2014-2024
4.1 Regional Breakdown of The Orphan CNS Drug Market
4.2 Leading National Markets: Revenue Forecasts, 2013-2024
4.3 The US: The Leading Market for Orphan CNS Drugs in 2012
4.3.1 Orphan Drug Regulations in the US
4.3.2 Benefits for Orphan Drug Developers
4.3.3 The US Orphan CNS Drug Market: Revenue Forecast, 2013-2024
4.4 Orphan Drugs in Leading EU Markets
4.4.1 The EU5 Orphan CNS Drug Market: Revenue Forecasting, 2013-2024
4.4.1.1 The Incentives for Orphan Drug Development in the EU
4.4.2 Orphan CNS Drugs in the EU5: Submarket Revenue Forecasts, 2013-2024
4.4.2.1 The German Orphan CNS Drug Market: Revenue Forecast, 2013-2024
4.4.2.2 The French Orphan CNS Drug Market: Revenue Forecast, 2013-2024
4.4.2.3 The UK Orphan CNS Drug Market: Revenue Forecast, 2013-2024
4.4.2.4 The Spanish Orphan CNS Drug Market: Revenue Forecast, 2013-2024
4.4.2.5 The Italian Orphan CNS Drug Market: Revenue Forecast, 2013-2024
4.5 The Japanese Orphan CNS Drug Market: Revenue Forecast, 2013-2024
4.5.1 Orphan Drug Regulations and Benefits in Japan
4.6 Potential for Orphan CNS Drugs in Emerging National Markets, 2013-2024
4.6.1 The Chinese Orphan CNS Drug Market: Revenue Forecast, 2013-2024
4.6.2 The Indian Orphan CNS Drug Market: Revenue Forecast, 2013-2024
4.6.2.1 Large Patient Population to Draw Drug Developers to India
4.6.3 The Russian Orphan CNS Drug Market: Revenue Forecast, 2013-2024
4.6.3.1 Attempts to Introduce Orphan Designation and Incentives 2010-2013
4.6.4 The Brazilian Orphan CNS Drug Market: Revenue Forecast, 2013-2024

5. Outlooks for Leading Orphan CNS Drugs 2014-2024
5.1 Huntington's Disease Treatments
5.1.1 Xenazine (Tetrabenazine; Lundbeck/Valeant Pharmaceuticals)
5.1.1.1 Omerus Pipeline HD Treatment Receives Orphan Designation
5.1.1.2 Xenazine: Revenue Forecast, 2013-2024
5.2 Amyotrophic Lateral Sclerosis Treatments
5.2.1 Rilutek (Riluzole; Covis Pharmaceuticals)
5.2.1.1 Patent Expiry to Cause Influx of Generic Treatments
5.2.1.2 Rilutek: Revenue Forecast, 2013-2024
5.3 Myasthenia Gravis Treatments
5.3.1 Mestinon (Pyridostigmine bromide; Valeant Pharmaceuticals)
5.3.1.1 Lack of Novel Treatments to Compete With Branded Drug
5.3.1.2 Mestinon: Revenue Forecast, 2013-2024
5.3.2 Imuran (Azathioprine; Prometheus Laboratories/Aspen Pharmacare)
5.3.2.1 Serious Adverse Events May Further Reduce Use of Imuran
5.3.2.2 Imuran: Revenue Forecast, 2013-2024

6. Orphan CNS Drugs: R&D Pipelines
6.1 Drugs in the Huntington's Disease Pipeline
6.1.1 ALN-HTT (Alnylam Pharmaceuticals/Medtronic Inc.): Drug-Device Combination Therapy
6.1.2 HD-02 (Avicena Group Inc.): Correcting the Body's Cellular Energy
6.1.3 CERE-120 (Ceregene Inc.): Delivering Neurotrophic Factors to Reverse Disease Process
6.1.4 Lead Compounds (Chaperone Therapeutics): Targeting Protein Misfolding
6.1.5 CX929 (Cortex Pharmaceuticals): Ampakine Treatment to Encourage Neuronal Growth
6.1.6 EPI-743 (Edison Pharmaceuticals): Redox Therapy in Preclinical Testing
6.1.7 GSK356278 (GSK): Respiration Treatment in Line for Additional HD Indication
6.1.8 Modified Antisense Oligo-Nucleotides (Isis Pharmaceuticals): Partnering with Roche to Aid Drug Discovery
6.1.9 NsG33 (Meteorin; NsGene A/S): Neurotrophic Protein Shown to Stimulate Neurite Growth in Preclinical Studies
6.1.10 LSD-1/MAO-B Inhibitor (Oryzon Genomics): Reducing Enzyme Activity May Provide Therapeutic Benefit
6.1.11 PBT2 (Prana Biotechnology): Targeting Metal-Protein Interactions to Reduce Protein Aggregation
6.1.12 PRO289 (Prosensa): Lowering Levels of Mutant Gene Proteins
6.1.13 RP103 (Raptor Pharmaceutical Corporation): Cysteamine Treatment Receives Orphan Designation
6.1.14 Zinc DNA Transcription Factors (Sangamo Biosciences/Shire AG): Switching Genes On and Off
6.1.15 Selisistat (SEN196; Siena Biotechnology): Orphan Drug Targeting Sirtuin Protein Inhibition in Phase II Development
6.1.16 Huntexil (Teva Pharmaceuticals): Neutralizing Dopaminergic Activity
6.2 Drugs in the Amyotrophic Lateral Sclerosis Pipeline, 2013
6.2.1 ALS-02, ALS-05 and ALS-08 (The Avicena Group): Designated Orphan Drug in Advanced Clinical Testing
6.2.2 NurOwn™ (BrainStorm Cell Therapeutics): Stem Cell Treatment to Replace Damaged Cells
6.2.3 Tirasemtiv (CK-2017357; Cytokinetics): Skeletal Muscle Activator Advances to Phase II Trials
6.2.4 E0302 (Mecobalamin; Eisai): Vitamin B12 Therapy Shown to Improve Muscle Wasting
6.2.5 Ozanezumab (GSK1223249; GSK): Monoclonal Antibody Treatment Recruiting Patients for Phase II Trial
6.2.6 Radicut (Edaravone; Mitsubishi Tanabe): Free Radical Scavenger in Advanced Trials
6.2.7 Region Specific Stem Cells (Neuralstem): Neuronal Stem Cell Therapy in Preclinical Testing
6.2.8 NP001 (Neuraltus Pharmaceuticals): Altering Macrophage Activity
6.2.9 sNN0029 (NeuroNova): Growth Factor Treatment Shown to Improve Muscle Strength
6.2.10 TDI-132 (Gilenya™; Novartis & The ALS Therapy Development Institute): Therapy to Counteract Aggressive Immune Cells
6.3 Drugs in the Myasthenia Gravis Pipeline, 2013
6.3.1 Soliris® (Eculizumab; Alexion Pharmaceuticals): Blood Disorder Treatment Investigated as Potential MG Therapy
6.3.2 BHT-3034 (Bayhill Therapeutics): Vaccine Therapy to Reverse Harmful Immune Responses
6.3.3 BKT130 (Biokine Therapeutics): Chemokine Inhibitor
6.3.4 CK-2017357 (Tirasemtiv; Cytokinetics): Designated Orphan Drug Tested in Multiple Indications

7. Orphan Drugs in CNS: Industry Trends, 2014-2024
7.1 Orphan Drugs in CNS: Strengths and Weaknesses, 2013-2024
7.2 Orphan Drugs in CNS: Opportunities and Threats, 2013-2024
7.3 Orphan Drugs in CNS: STEP Analysis, 2013-2024
7.3.1 Social Factors
7.3.1.1 Ethical Considerations in Funding Orphan Drug Development
7.3.2 Technological Developments
7.3.2.1 Increased Understanding of Disease Will Drive Innovation
7.3.3 Economic Pressures
7.3.3.1 Discounts in Drug Prices Will Increase Accessibility
7.3.4 Political Issues
7.3.4.1 Harmonising Global Regulatory Pathways
7.4 Trends in Orphan CNS Drug Development
7.4.1 Clinical Trials for Orphan Drugs
7.4.1.1 Are Adverse Events More Acceptable for Orphan Drugs?
7.4.1.2 Challenges and Opportunities in Patient Recruitment
7.4.2 Biomarkers for Orphan CNS Indications
7.4.2.1 Companion Diagnostics: Driving Personalised Medicine
7.4.3 The Role of Public Funding in Orphan Drug Development
7.5 Commercialising Orphan Drugs in CNS
7.5.1 Pricing of Orphan Drugs May Become Crucial to Success
7.5.2 Market and Patient Access Are Crucial for Orphan Drug Success
7.5.3 Repositioning Drugs for Orphan CNS Indications
7.5.3.1 Expanding Beyond Orphan Indications
7.5.4 Big Pharma and Orphan Drugs
7.5.4.1 Orphan Drugs Fit the Personalised Medicine Model
7.5.5 Common Market Entry Strategies
7.5.6 Orphan Indications as an Opportunity for Generic Drug Manufacturers

8. Research Interviews
8.1 Dr Tsao-Nivaggioli, CEO and Board Member, Avicena Group
8.1.1 Avicena Group
8.1.2 Rare Diseases and Applying for Orphan Drug Status
8.1.3 HD-02: Targeting the Body's Cellular Energy Systems
8.1.4 Challenges in Developing Orphan Drugs
8.1.5 Future Growth Opportunities and Perspective for the Market
8.2 Respondent from Edison Pharmaceuticals
8.2.1 Edison Pharmaceuticals
8.2.2 Defining Orphan Disease and Drug Submissions in Target Markets
8.2.3 The Market Potential (and Risk) of Pursuing Treatments for Mitochondrial Diseases
8.2.4 Company Alliances and Future Prospects for the Market

9. Conclusions from Our Study
9.1 The State of the Orphan CNS Drugs Market
9.2 Renewed Interest in Rare CNS Diseases will Stimulate that Market
9.3 The US will Maintain its Market Dominance from 2014-2024
9.4 High Price of Treatments May Limit Market Potential

List of Tables
Table 1.1 Currency Exchange Rates
Table 1.2 Common Abbreviations Used in this Report
Table 2.1 EU Prevalence Statistics for Selected Rare CNS Indications, 2013
Table 3.1 Global Orphan CNS Drug Market: Revenue ($m) and Market Share (%) by Sector, 2012
Table 3.2 Global Orphan CNS Drug Market: Overall Market and Revenue Forecasts by Sector ($m, AGR %, CAGR %), 2013-2024
Table 3.3 Global Orphan CNS Drug Market: Submarket Shares (%), 2012-2024
Table 3.4 Huntington's Disease Submarket: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 3.5 Amyotrophic Lateral Sclerosis Submarket: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 3.6 Myasthenia Gravis Submarket: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 4.1 Global Orphan CNS Drug Market: Revenue ($m) and Market Share (%) by Region, 2012
Table 4.2 Global Orphan CNS Drug Market: Revenue Forecasts ($m, AGR %, CAGR %) by Region, 2013-2024
Table 4.3 Global Orphan CNS Drug Market: Regional Submarket Shares (%),2012-2024
Table 4.4 US Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 4.5 EU5 Orphan CNS Drug Market: Revenue ($m) and Market Share (%) by Country, 2012
Table 4.6 EU5 Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %) by Country, 2013-2024
Table 4.7 Fee Reductions (%) Available for SMEs Developing Orphan Drugs in the EU, 2013
Table 4.8 German Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 4.9 French Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 4.10 UK Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 4.11 Spanish Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 4.12 Italian Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 4.13 Japanese Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 4.14 Chinese Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 4.15 Indian Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 4.16 Russian Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 4.17 Brazilian Orphan CNS Drug Market: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 5.1 Top Orphan CNS Drugs: Revenues ($m) and Leading Revenue Shares (%), 2012
Table 5.2 Xenazine: Revenue ($m), 2009-2012
Table 5.3 Xenazine: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 5.4 Rilutek: Revenue ($m), 2010-2012
Table 5.5 Rilutek: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 5.6 Mestinon: Revenue ($m), 2010-2012
Table 5.7 Mestinon: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 5.8 Imuran: Revenue ($m), 2008-2012
Table 5.9 Imuran: Revenue Forecast ($m, AGR %, CAGR %), 2013-2024
Table 6.1 Selected Pipeline Candidates in Development for Huntington's Disease, 2012
Table 6.2 Selected Pipeline Candidates in Development for ALS, 2013
Table 6.3 Selected Pipeline Candidates in Development for Myasthenia Gravis, 2013
Table 7.1 Global Orphan CNS Drug Market: Strengths and Weaknesses, 2013-2024
Table 7.2 Global Orphan CNS Drug Market: Opportunities and Threats, 2013-2024
Table 9.1 Global Orphan CNS Drug Market: Revenue ($m, CAGR %), and Market Share (%) by Sector, 2012, 2018 & 2024
Table 9.2 Global Orphan CNS Drug Market: Revenue ($m, CAGR %) and Market Share (%) by Region, 2012, 2018 & 2024

List of Figures
Figure 2.1 Orphan Disease Prevalence by Country/Region, 2013
Figure 2.2 Orphan Drugs Clinical Pipeline by Therapeutic Category, 2012
Figure 2.3 Orphan Drug Designation Benefits in Major Markets, 2013
Figure 3.1 Orphan Drug Approvals in the US, 2000-2013
Figure 3.2 Global Orphan CNS Drug Market: Share (%) by Sector, 2012
Figure 3.3 Global Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 3.4 Global Orphan CNS Drug Market: Submarket Shares (%), 2018
Figure 3.5 Global Orphan CNS Drug Market: Submarket Shares (%), 2024
Figure 3.6 Global Orphan CNS Drug Market: Drivers and Restraints, 2014-2024
Figure 3.7 Huntington's Disease Market: Revenue Forecast ($m), 2013-2024
Figure 3.8 Amyotrophic Lateral Sclerosis Market: Revenue Forecast ($m), 2013-2024
Figure 3.9 Myasthenia Gravis Market: Revenue Forecast ($m), 2013-2024
Figure 4.1 Global Orphan CNS Drug Market: Share (%) by Region, 2012
Figure 4.2 Global Orphan CNS Drug Market: Share (%) by Region, 2018
Figure 4.3 Global Orphan CNS Drug Market: Share (%) by Region, 2024
Figure 4.4 US Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 4.5 EU5 Orphan CNS Drug Market: Share (%) by Country, 2012
Figure 4.6 EU5 Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 4.7 German Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 4.8 French Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 4.9 UK Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 4.10 Spanish Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 4.11 Italian Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 4.12 Japanese Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 4.13 Chinese Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 4.14 Indian Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 4.15 Russian Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 4.16 Brazilian Orphan CNS Drug Market: Revenue Forecast ($m), 2013-2024
Figure 5.1 Top Orphan CNS Drug: Revenue Shares (%), 2012
Figure 5.2 Xenazine: Revenue ($m), 2009-2012
Figure 5.3 Xenazine: Revenue Share (%) by Region, 2012
Figure 5.4 Xenazine: Revenue Forecast ($m), 2013-2024
Figure 5.5 Rilutek: Revenue ($m), 2010-2012
Figure 5.6 Rilutek: Revenue Forecast ($m), 2013-2024
Figure 5.7 Mestinon: Revenue ($m), 2010-2012
Figure 5.8 Mestinon: Revenue Forecast ($m), 2013-2024
Figure 5.9 Imuran: Revenue ($m), 2008-2012
Figure 5.10 Imuran: Revenue Forecast ($m), 2013-2024
Figure 9.1 Global Orphan CNS Drug Market: Revenue ($m) by Sector, 2012, 2018 & 2024
Figure 9.2 Global Orphan CNS Drug Market: Revenue ($m) by Region, 2012, 2018 & 2024