ABOUT DATAMONITOR HEALTHCARE 2
About the CNS pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the myasthenia gravis market 3
Contributing experts 5
Related reports 5
Key metrics 6
CHAPTER 2 MARKET OVERVIEW 8
Definition of myasthenia gravis 9
Disease overview 9
Classification of myasthenia gravis subtypes 9
Age of onset 10
Presence or absence of anti-acetylcholine antibodies 10
Presence of muscle-specific receptor tyrosine kinase (MuSK) antibodies 10
Severity 10
Symptoms of myasthenia gravis 11
Diagnosis of myasthenia gravis 12
Anti-acetylcholine receptor antibodies 12
Edrophonium testing 12
Electrophysiological testing 12
Etiology of myasthenia gravis 13
Prognosis 14
Epidemiology of myasthenia gravis 15
More prevalent than Huntington's disease or amyotrophic lateral sclerosis 15
Trends in myasthenia gravis epidemiology 16
Prevalence of myasthenia gravis 16
Few epidemiology studies have been conducted investigating the prevalence of myasthenia gravis 16
Population size and prevalence rate of myasthenia gravis 18
Small patient population hinders research 18
Treatment tree 19
Datamonitor's myasthenia gravis treatment tree 19
First-line - Mestinon 20
Second-line therapy - Steroid immunosuppression or thymectomy 20
Third-, fourth- and fifth-line therapy 23
Short-term therapies 23
Published treatment algorithms and recommendations 23
Current market value and trends 26
Cost of current treatments 28
Unmet need in myasthenia gravis 29
More favorable dosing regimens 30
Improved side-effect profiles 31
Polytherapy adds to side-effect burden 31
Mestinon (pyridostigmine) 32
Prednisolone and Prednisone 32
Drug-free remission 33
Quicker onset of action 34
Quicker diagnosis 35
Commercial viability of the myasthenia gravis market 36
Positive commercial attributes of the disease 36
High unmet need 36
Chronic condition 37
Well understood etiology 37
Low competition 37
Defined patient groups and markets 37
Low generic competition 38
Negative commercial attributes of the disease 39
Most patients respond to current treatments 39
Cost of care is not particularly high 39
Not typically life-threatening 39
Patient population is small 40
Leading brand - Mestinon 40
Seven major market sales for 2004-07 41
Generic incursion in the US drives down brand sales 42
Mestinon sales constitute over half of the total myasthenia gravis market 42
Forecast to 2017 43
Clinical profile 44
Side-effect profile is undesirable 45
Three dosage formulations of Mestinon are available 46
Patients may take up to 25 tablets a day 46
Key opinion leader-reported typical dosing regimens 47
CHAPTER 3 FUTURE MARKET POTENTIAL 48
Future market 49
Base scenario - EN101 only proving to be a symptomatic treatment 49
Steroid-sparing scenario 51
Non EN101 scenario 54
CHAPTER 4 PIPELINE OVERVIEW AND DYNAMICS 55
Pipeline drugs market potential 56
Pipeline overview 57
Classification of pipeline products 58
CHAPTER 5 CLINICAL-STAGE DRUG ANALYSIS & FORECASTS 59
EN101 60
Drug overview 60
Forecasts to 2017 60
Market penetration 61
Marketing factors 66
EN101 pricing assumptions - two scenarios 66
Marketing resources 71
Patient potential 73
Satisfaction of unmet needs 73
More favorable dosing regimens 73
Improved side-effect profile 74
Quicker onset of action 74
Clinical trial data 75
Interim analysis of Phase IIa trial 75
Completed Phase Ib trial 76
Scientific background 78
RNA therapy 78
Oral delivery of RNA therapies is a challenge 78
Animal model suggests that EN101 does reach muscles when administered orally 79
Preclinical investigations 79
Rituxan (rituximab) 81
Drug overview 81
Forecast to 2017 81
Marketing factors 84
Cost of Rituxan/MabThera in the seven major markets 85
Patient population 86
Patient population for Rituxan is very small 86
Satisfaction of unmet needs 88
More favorable dosing regimens 88
Drug-free remission 88
Clinical trial data 88
Other drugs in clinical development for myasthenia gravis 89
Kenketsu Venoglobulin-IH (Polyethylene Glycol Treated Human Normal Immunoglobulin) 89
Drug overview 89
Eculizumab 90
Drug overview 90
Hematopoietic stem cell therapy 90
Drug overview 90
BIBLIOGRAPHY 92
Journals 92
Websites 94
APPENDIX 97
Data definitions, limitations and assumptions 97
Standard Units 97
Japanese market data 97
Derivation of sales forecasts and pricing trends 97
Forecast methodology 98
Product forecasts - Base scenario 98
Product forecasts - steroid-sparing scenario 98
Contributing experts 99
About Datamonitor 99
About Datamonitor Healthcare 99
About the CNS analysis team 100
Disclaimer 102
List of Tables
Table 1: Patient populations of the three neurological diseases covered in Datamonitor's orphan disease series, 2008 16
Table 2: Population size and prevalence rate of myasthenia gravis across the seven major markets, 2008 18
Table 3: Barohn (2008) treatment recommendations for myasthenia gravis, 2008 23
Table 4: Annual cost of therapy for myasthenia gravis in the US, 2007 29
Table 5: Neurological conditions with similar symptoms to myasthenia gravis 35
Table 6: Commercial viability of the myasthenia gravis market, 2008 36
Table 7: R&D clinical-stage pipeline in myasthenia gravis, 2008 57
Table 8: Methodologies for EN101 forecasts in the seven major markets, 2008 63
Table 9: Datamonitor's EN101 pricing at launch in the US, Japan and 5EU 67
Table 10: Cost of symptomatic neurology drugs with orphan disease status in the US, 2007 68
Table 11: Cost of disease-modifying neurology drugs in the US, 2007 71
Table 12: Cost of Rituxan/MabThera in the US and 5EU for the treatment of myasthenia gravis, 2008 85
List of Figures
Figure 1: Seven major market myasthenia gravis market size, 2004-2017 6
Figure 2: Myasthenia gravis treatment tree derived from Datamonitor's primary and secondary research, 2008 19
Figure 3: Hilton-Jones (2007) treatment algorithm for ocular myasthenia 2007 24
Figure 4: Hilton-Jones (2007) treatment algorithm for generalized myasthenia, 2007 25
Figure 5: Myasthenia gravis-specific sales revenue in the US, Japan and 5EU, 2004-07 26
Figure 6: Myasthenia gravis-specific sales volume (IMS Standard Units) in the US, Japan and 5EU, 2004-07 27
Figure 7: Regional share of myasthenia gravis sales in the seven major markets, 2007 28
Figure 8: Unmet need in myasthenia gravis treatment, 2008 30
Figure 9: Mestinon myasthenia gravis-specific sales ($m), 2004-07 41
Figure 10: Mestinon (pyridostigmine hydroxide) and pyridostigmine hydroxide generics by volume of IMS Standard Units sold, 2004-07 42
Figure 11: Pyridostigmine (Mestinon and generics) share of the myasthenia gravis market across the seven major markets, 2004-07 43
Figure 12: Mestinon (pyridostigmine) sales ($m) forecast in the seven major markets, 2007-2017 44
Figure 13: Myasthenia gravis total market forecast to 2017 across the seven major markets; base scenario - EN101 symptomatic treatment only 50
Figure 14: Estimated number of myasthenia gravis patients taking each treatment in the US; base scenario - EN101 symptomatic treatment only, 2004-2017 51
Figure 15: Myasthenia gravis total market forecast to 2017 across the seven major markets; EN101 steroid-sparing scenario 52
Figure 16: Estimated number of myasthenia gravis patients taking each treatment in the US in Datamonitor's EN101 steroid sparing scenario, 2004-2017 53
Figure 17: Myasthenia gravis total market forecast to 2017 across the seven major markets; No EN101 scenario 54
Figure 18: Summary of myasthenia gravis pipeline drugs potential ($m), 2008-2017 56
Figure 19: Number of patients forecast to receive EN101 across the seven major markets, 2010-17 64
Figure 20: EN101 sales revenue ($m) forecast for myasthenia gravis across the seven major markets, 2010-17 65
Figure 21: Number of patients forecast to receive Rituxan (rituximab) across the seven major markets, 2009-2017 83
Figure 22: Rituxan (rituximab) sales revenue ($m) forecast for myasthenia gravis across the seven major markets, 2009-17 84