Table of Contents

ABOUT DATAMONITOR HEALTHCARE 2
About the Central Nervous System pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Contributing experts 4
Datamonitor insight into the ADHD market 4
CHAPTER 2 MARKET OVERVIEW AND POTENTIAL 10
Disease definition 11
Etiology of ADHD 11
Genetic predisposition 11
Neurotransmitter dysfunction 12
Acquired brain lesions and structural abnormalities 13
Environmental influence 13
Diagnostic criteria of ADHD 14
Epidemiology of ADHD 16
ADHD is estimated to affect over 37 million people in the seven major markets 16
The adult ADHD population is twice the size of the current pediatric population 20
Key patient segments 21
ADHD is more prevalent in boys than girls 21
ADHD carries a high risk of co-morbidity 22
ADHD negatively impacts on quality of life 25
Clinical unmet needs of ADHD 25
More effective medications for patients who do not respond to stimulants 27
Efficacy in the absence of insomnia 28
Improved compliance 29
Diagnostic unmet needs of ADHD 30
Developmentally appropriate diagnostic criteria at older ages 30
Current treatment classes and mechanisms 31
Treatment algorithm 31
Pharmacological treatment 32
Psychosocial therapy 34
Current market value and future market forecasts 35
The ADHD market has grown consistently over the last 4 years 35
The US dominates the ADHD market with a 94% market share 36
Shire's Adderall XR continues to reign as market leader 38
There exists seasonal variation in uptake of ADHD drugs 40
The ADHD market is set to grow throughout the forecast period 42
Near-term growth (2008-2010) - continued strong growth followed by decline in sales 43
Medium-term growth (2010-2015) - continued growth driven by ongoing uptake of marketed drugs 43
Long-term outlook (2015-2017) - patent expiries take their toll 43
CHAPTER 3 GLOBAL OPPORTUNITIES AND THREATS 44
Key opportunities 45
Opportunities for growth remain in the adult ADHD market 45
There remains room in the market for further patch formulations 48
Substantial commercial potential exists for efficacious non-stimulant 48
Garner competitive edge by targeting cognition 48
Key threats 49
Less acceptance of pharmaceutical intervention in non-US markets 49
Increasing presence of leading players is a barrier to market entry 51
CHAPTER 4 BRAND DYNAMICS AND LEADING COMPARATOR THERAPIES 53
Marketed brands overview 54
Adderall and Adderall XR (amphetamine) 55
Drug overview 56
Forecasts to 2017 57
SWOT analysis 59
Clinical trial data 59
Adderall XR's clinical trial program and study designs 60
Efficacy of Adderall XR 60
Adderall side effects 62
Mechanism of action 63
Concerta (methylphenidate) 63
Concerta drug overview 63
Forecasts to 2017 65
SWOT analysis 66
Clinical trial data 67
Concerta's clinical program and study designs 67
Efficacy of Concerta 67
Concerta demonstrates efficacy in treating adult ADHD 68
Concerta side effects 68
Mechanism of action 69
Strattera (atomoxetine) 69
Drug overview 70
Forecasts to 2017 72
SWOT analysis 73
Clinical trial data 73
Strattera clinical program and study designs 74
Efficacy of Strattera 74
Strattera efficacious in improving ADHD symptoms in patients with co-morbid alcohol abuse 74
Side effects of Strattera 74
Mechanism of action 75
Focalin and Focalin XR (dexmethylphenidate) 75
Drug overview 75
Forecasts to 2017 77
SWOT analysis 78
Clinical trial data 78
Focalin XR clinical program and study designs 78
Efficacy of Focalin XR 79
Side effects of Focalin XR 79
Mechanism of action 80
Metadate (methylphenidate hydrochloride) 80
Drug overview 80
Forecasts to 2017 82
SWOT analysis 83
Clinical trial data 84
Metadate CD's clinical trial program and study designs 84
Efficacy of Metadate CD 84
Side effects of Metadate CD 85
Daytrana (methylphenidate) 85
Drug overview 85
Forecasts to 2017 88
SWOT analysis 89
Clinical trial data 89
Daytrana's clinical trial program and study designs 89
Efficacy of Daytrana 90
Side effects of Daytrana 90
Vyvanse (lisdexamfetamine dimesylate) 90
Drug overview 90
Forecasts to 2017 93
SWOT analysis 94
Clinical trial data 94
Vyvanse clinical program and study designs 95
Efficacy of Vyvanse 95
Vyvanse demonstrates equivalent efficacy and duration of action to Adderall XR 95
Phase III trial demonstrates Vyvanse's efficacy in adult patients 95
Side effects of Vyvanse 96
Ritalin (methylphenidate hydrochloride) 96
Drug overview 96
Forecasts to 2017 99
SWOT analysis 100
Clinical trial data 100
Ritalin LA clinical program and study designs 101
Efficacy of Ritalin 101
Side effects of Ritalin LA 101
CHAPTER 5 FORECAST ANALYSIS 102
Key events 103
Product launches in the US and 5EU 104
Key drug launch assumptions 104
Product launches in Japan 107
Strattera 107
Patent expiries 107
Adderall XR 108
Focalin XR 109
Ritalin LA 109
Concerta 110
Strattera 110
Data definitions, limitations and assumptions 111
Standard units 111
Japanese market data 111
Derivation of sales forecasts and pricing trends 111
Forecast methodology 111
CHAPTER 6 PIPELINE OVERVIEW - R&D DYNAMICS AND APPROACH 112
Pipeline overview 113
Classification of pipeline products 114
Alpha-adrenergic agonists 114
Amphetamines 114
Nicotinic agonists 115
Other drug classes 115
Clinical trial design 115
Primary clinical trial endpoints in ADHD 116
ADHD Rating Scale 116
Conners Global Index - Parent and Teacher Forms (CGI-P & CGI-T) 116
SKAMP behavioral rating scale 116
The IOWA Conners Rating Scale 116
Adult ADHD Investigator Symptom Rating Scale (AISRS) 117
Conners Adult ADHD Rating Scale - Self-report (CAARS-S:S) 117
Secondary clinical trial endpoints in ADHD 118
Clinical Global Impression Improvement Scale 118
Child Health Questionnaire 118
Key considerations in clinical trial design 119
Participant sample 119
Objective clinical trial endpoints 120
Regulatory barriers to the development of pediatric medications 120
Non-regulatory barriers to the development of pediatric medications 121
CHAPTER 7 LATE-STAGE DRUG ANALYSIS & FORECASTS 123
Late-stage pipeline overview 124
Alpha adrenergic agonist pipeline drugs 127
Pipeline summary 127
Intuniv (guanfacine hydrochloride) 127
Drug overview 128
Forecasts to 2017 129
Marketing factors 130
Patient potential 134
Clinical trial data 135
Clonicel (clonidine hydrochloride) 139
Drug overview 139
Forecasts to 2017 139
Marketing factors 141
Patient potential 142
Clinical trial data 143
Amphetamine pipeline drugs 144
Liquadd 144
Drug overview 144
Forecasts to 2017 145
Marketing factors 146
Patient potential 147
Satisfaction of unmet needs 147
Clinical trial data 147
SPD-465 148
Drug overview 148
Forecasts to 2017 148
Marketing factors 150
Patient potential 151
Clinical trial data 152
Nicotinic acetylcholine receptor agonists 154
Pipeline summary 154
GTS-21 155
ABT-089 156
ABT-894 156
Other pipeline drugs 157
Pipeline summary 157
MK-0249 158
NRC 071A 158
Abilify (aripiprazole) 158
NS2359/GSK372475 159
Recently suspended/discontinued drugs 159
CX717 159
Sparlon (modafinil) 160
CHAPTER 8 COMMERCIAL IMPACT AND LIFECYCLE MANAGEMENT: CASE STUDIES 161
Introduction 162
Focus on ADHD provides long-term growth 162
Timely launch of Adderall XR was a winning strategy for Shire 163
The future of Shire's ADHD franchise depends on a successful switch to Vyvanse 164
Daytrana's novel delivery formulation has diversified Shire's ADHD franchise 166
As the first patch formulation approved for ADHD, Daytrana offers convenient and flexible dosing 166
Daytrana serves to reduce Shire's reliance on Vyvanse as a follow-on product to Adderall XR 167
There is room in the market for further patch formulations 168
Continued development of new treatments demonstrates long-term commitment 169
Concerta - a successful launch strategy 170
First-to-market status of the once-daily treatments provided firm grounding for growth 170
EU launch maximized the commercial potential of Concerta 171
Focus promotional spend on maintaining relationships with prescribers 171
J&J should look to in-licensing if it is to maintain long term market share 172
Seasonal factors should be considered at drug launch 173
BIBLIOGRAPHY 175
Journal papers, books, and conference abstracts 175
Websites 186
Datamonitor reports 195
APPENDIX 196
Report methodology 196
Contributing experts 198
About Datamonitor 198
About Datamonitor Healthcare 198
About the Disease analysis team 199
Disclaimer 201
List of Tables
Table 1: Symptoms for ADHD/HKD in the DSM-IV and ICD-10 14
Table 2: Definition of ADHD in the DSM-IV 15
Table 3: Results of epidemiology studies of ADHD across the seven major markets 16
Table 4: Prevalence of ADHD in the seven major markets, 2008 19
Table 5: Performance of the US, 5EU and Japan ADHD markets, 2006-7 37
Table 6: Adderall/Adderall XR: key facts, 2008 57
Table 7: Concerta: key facts, 2008 64
Table 8: Strattera: key facts, 2008 71
Table 9: Focalin/Focalin XR: key facts, 2008 76
Table 10: Metadate CD: key facts, 2008 81
Table 11: Daytrana: key facts, 2008 87
Table 12: Vyvanse: key facts 92
Table 13: Ritalin franchise: key facts 98
Table 14: Forecast launch dates in the US and 5EU 104
Table 15: Forecast launch dates in Japan 107
Table 16: Key patent expiries for key marketed drugs in the US and 5EU 107
Table 17: Drugs in early stage development for ADHD, 2008 113
Table 18: Key pipeline drugs in late-stage development for ADHD, 2008 126
Table 19: Key late-stage development pipeline, alpha receptor agonist, 2008 127
Table 20: Factors impacting on the revenues of Intuniv, 2008-2017 129
Table 21: Factors impacting on the revenues of Clonicel, 2008-2017 140
Table 22: Factors impacting on the revenues of Liquadd, 2008-2017 145
Table 23: Factors impacting on the revenues of SPD-465, 2008-2017 149
Table 24: Key late-stage development pipeline for ADHD, nicotinic agonists, 2008 154
Table 25: Key late-stage development pipeline, other classes, 2008 157
Table 26: Shire's ADHD pipeline, 2008 169
Table 27: Datamonitor drug assessment parameters 197
List of Figures
Figure 1: Drug assessment summary overview of key marketed and pipeline ADHD drugs, 2008 7
Figure 2: Historical (2004-07) and forecast (2008-17) ADHD sales revenue for key marketed and pipeline drugs across the 7MM 8
Figure 3: Prevalence of ADHD co-morbidities in the MTA study 24
Figure 4: Key unmet clinical need in the treatment of ADHD 27
Figure 5: Revenues of ADHD drugs, 7MM, 2004-07 36
Figure 6: Revenue market share of the leading branded ADHD drugs, 2004-07 39
Figure 7: US sales revenues for ADHD drugs, 2004-07 41
Figure 8: ADHD market value in the US, Japan and 5EU, 2004-17 42
Figure 9: Sales revenue ($m) of ADHD drugs prescribed for pediatric, adolescent and adult patients, 2004-07 45
Figure 10: Growth of sales revenue ($m) of drugs prescribed for pediatric, adolescent and adult ADHD in the US, 2004-07 47
Figure 11: Sales revenue garnered by key players in the ADHD market (2006-2007 estimates), 2008-17 forecasts 52
Figure 12: Current key marketed drugs - clinical and commercial attractiveness, 2008 54
Figure 13: Historical (2004-07) and forecast (2008-2017) ADHD sales revenue for key marketed and pipeline drugs across the 7MM 55
Figure 14: Adderall and Adderall XR ADHD-specific sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-2017 forecasts 58
Figure 15: Adderall XR: SWOT analysis, 2008 59
Figure 16: Concerta sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-2017 forecasts 65
Figure 17: Concerta: SWOT analysis 66
Figure 18: Strattera sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-2017 forecasts 72
Figure 19: Strattera: SWOT analysis 73
Figure 20: Focalin XR revenue ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 77
Figure 21: Focalin XR: SWOT analysis 78
Figure 22: Metadate CD sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 82
Figure 23: Metadate CD: SWOT analysis 83
Figure 24: Daytrana sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 88
Figure 25: Daytrana: SWOT analysis 89
Figure 26: Vyvanse sales revenue ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 93
Figure 27: Vyvanse: SWOT analysis 94
Figure 28: Ritalin LA sales ($m) across the 7MM, 2006-07 estimates, 2008-17 forecasts 99
Figure 29: Ritalin LA: SWOT analysis 100
Figure 30: Impact of each key event on the ADHD market across the seven major markets, 2008-2017 103
Figure 31: Drugs in late-stage development for ADHD by class, 2008 113
Figure 32: Comparative late-stage pipeline ADHD drug sales revenue forecast, 2008-2017 125
Figure 33: Sales forecast of Intuniv in the 7MM, 2007-2017 129
Figure 34: Intuniv drug assessment summary, 2008 130
Figure 35: Sales forecast of Clonicel in the 7MMs, 2007-2017 140
Figure 36: Clonicel drug assessment summary, 2008 141
Figure 37: Sales forecast of Liquadd in the 7MMs, 2007-2017 145
Figure 38: Liquadd drug assessment summary 146
Figure 39: Sales forecast for SPD-465 in the 7MMs 148
Figure 40: SPD-465 drug assessment summary, 2008 150
Figure 41: Shire ADHD franchise forecast ($m), 2008-17 162
Figure 42: Vyvanse's drug homepage 165
Figure 43: Promotional spend on physician detailing for key ADHD products in the US and 5EU, 2004-06 172
Figure 44: Seasonal revenue growth and decline of ADHD drug 173