Pipeline and Commercial Insight: Anxiety Disorders - Viable indication for antipsychotics companies

Pipeline and Commercial Insight: Anxiety Disorders - Viable indication for antipsychotics companies

Introduction

Despite forming the mainstay of pharmacological treatment of anxiety disorders, response rates to serotonergic-based treatments are often less than robust. As such, physicians are increasingly looking towards novel drugs. For pharmaceutical companies, the pressure to meet this need and maintain market share is growing as the patent expiries of three major brands draws near.

Scope

*Analysis of key marketed brands and late-stage pipeline drugs.

*Anxiety disorders-specific drug sales volume and value forecasts to 2017 in the US, Japan, and five major European markets.

*Identification of future market events that are expected to affect anxiety disorders drug revenues.

*Analysis of patient potential, unmet needs and clinical trial design in anxiety disorder.

Highlights

Atypical antipsychotics are expected to change the landscape of the future anxiety disorders market, with Seroquel XR set to benefit from first-to-market status upon approval in generalized anxiety disorder. Seroquel XR will be positioned as a second/third-line treatment for patients who have failed to respond to available antidepressants.

In view of the high co-morbidity between anxiety and depression, it remains in the interests of antidepressant manufacturers to maximize the patient potential of their products. However, with three key brands set to experience patent expiration over the forecast period (20082017), competition within the antidepressant drug classes will intensify.

The presence of neurokinin (NK) receptor antagonists and corticotrophin releasing factor (CRF) antagonists in the anxiety disorders pipeline have generated much interest among interviewed key opinion leaders. Datamonitor regards NK receptor antagonists as holding the greatest promise in the treatment of anxiety disorders.

Reasons to Purchase

*Understand the current anxiety disorder market dynamics and how they are expected to evolve out to 2017.

*Benchmark key late-stage pipeline anxiety disorder compounds against the current market leading brands.

*Understand unmet needs in the anxiety disorders market based on key opinion leader comments.

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 5
Datamonitor insight into the anxiety disorders market 6
Related reports 9
Upcoming reports 9
CHAPTER 2 PATIENT POTENTIAL 11
Definition of anxiety disorders 12
Classification of anxiety disorders 12
ICD-10 classification 13
DSM-IV classification 14
Etiology of anxiety disorders 14
Generalized anxiety disorder 15
Panic disorder 15
Social anxiety disorder 16
Obsessive-compulsive disorder 16
Post-traumatic stress disorder 17
Agoraphobia 18
Specific phobias 18
Acute stress disorder 19
Epidemiology of anxiety disorders 19
Anxiety disorders are the most prevalent psychiatric conditions 19
Generalized anxiety disorder 22
Panic disorder 24
Social anxiety disorder 26
Obsessive-compulsive disorder 28
Post-traumatic stress disorder and acute stress disorder 30
Agoraphobia 33
Specific phobias 34
Other anxiety disorders 36
Key patient segments 36
Acute versus chronic anxiety 36
Anxiety disorders are twice as prevalent among women 38
Greater research is required to elucidate reasons for the greater prevalence of anxiety disorders in women 38
Anxiety disorders are characterized by an early age of onset 39
Co-morbidity is a fundamental feature of anxiety disorders 40
Depression is the most common co-morbid condition of anxiety 41
Clinical unmet needs in anxiety disorders 43
Improvement in response and remission rates 43
Limiting side effects is essential 46
Improving patient compliance 47
Diagnostic unmet needs in anxiety disorders 48
Need to increase low diagnosis rates 48
Raising awareness of anxiety disorders is necessary 51
CHAPTER 3 MARKET OVERVIEW 54
Current treatment classes and mechanisms 55
Most treatment guidelines recommend SSRIs as first-line treatment for anxiety disorders 55
Pharmacological treatments 55
Non-pharmacological treatment 59
Current market assessment 60
The anxiety disorders market was worth $4.1 billion in 2007 60
Despite experiencing the greatest decline in sales, the US remained the largest market in 2007 62
Antidepressants and mood stabilizers achieve the greatest sales revenue, while tranquillizers dominate volume sales 64
The top six brands constitute only 44% of the total market 65
Mixed anxiety and depressive disorders account for a quarter of market value in 2007 69
Future market assessment 70
The anxiety disorders market is set to experience modest growth over the forecast period 2008-2017 70
CHAPTER 4 BRAND DYNAMICS 75
Marketed brands overview 76
Lexapro (escitalopram, Lundbeck/Forest) 78
Drug overview 78
Forecasts to 2017 81
SWOT analysis 83
Clinical trial data 83
Generalized anxiety disorder 83
Panic disorder 85
Social anxiety disorder 85
Obsessive-compulsive disorder 86
Lexapro side effects 87
Effexor/Effexor XR (venlafaxine, Wyeth) 88
Drug overview 88
Forecasts to 2017 90
SWOT analysis 92
Clinical trial data 92
Generalized anxiety disorder (GAD) 93
Social anxiety disorder 94
Panic disorder 95
Effexor XR side effects 96
Cymbalta (duloxetine, Eli Lilly) 97
Drug overview 97
Forecasts to 2017 99
SWOT analysis 101
Clinical trial data 102
Generalized anxiety disorder (GAD) 102
Cymbalta side effects 103
Paxil/Paxil CR (paroxetine, GlaxoSmithKline) 104
Paxil/Paxil CR drug overview 104
Forecasts to 2017 107
SWOT analysis 108
Clinical trial data 108
Social anxiety disorder 108
Panic disorder 109
Paxil CR side effects 110
Xanax/Xanax XR (alprazolam, Pfizer) 111
Drug overview 111
Forecasts to 2017 113
SWOT analysis 114
Clinical trial data 114
Panic disorder 115
Side effects of Xanax XR 116
Lyrica (pregabalin, Pfizer) 117
Drug overview 117
Forecasts to 2017 119
SWOT analysis 120
Clinical trial data 122
Generalized anxiety disorder (GAD) 123
Side effects of Lyrica 124
CHAPTER 5 PIPELINE OVERVIEW - R&D DYNAMICS AND APPROACH 125
Pipeline overview 126
GlaxoSmithKline has a strong presence in the late-stage anxiety disorders pipeline 126
Gamma-aminobutyric acid (GABA) modulators represent the most prevalent drug class in early-stage development 129
Classification of pipeline products 132
Corticotrophin releasing factor antagonists 132
Neurokinin receptor antagonists 133
NMDA receptor modulators 133
Other drug classes 133
Discontinued and suspended projects 134
Pexacerfont (BMS-562086) 134
Amibegron (SR-58611A) 134
Clinical trial design in anxiety disorders 134
Key considerations in clinical trial design of anxiety disorder trials 135
Results from studies which exclude patients with co-morbid psychiatric conditions have limited relevance to the naturalistic population 135
Progress is being made in clarifying the term "remission" 136
Clinical trial design guidance 137
Inclusion criteria 137
Exclusion criteria 138
Assessing efficacy 138
Key research recommendations 139
Primary clinical trial endpoints and anxiety rating scales 139
Hamilton Anxiety Scale 139
Hospital Anxiety and Depression Scale 140
Liebowitz Social Anxiety Scale 140
Social Phobia and Anxiety Inventory (SPAI) 140
Social Phobia Inventory (SPIN) 141
Clinician-Administered PTSD Scale 141
Treatment Outcome PTSD Scale 141
Davidson Trauma Scale 142
Short PTSD Rating Interview 142
Brief Social Phobia Scale 142
Panic Disorder Severity Scale 142
Panic and Agoraphobia Scale 143
Yale-Brown Obsessive-Compulsive Scale 143
Secondary clinical trial endpoints in anxiety disorders 143
Patient Global Impression of Improvement scale 143
Clinical Global Impression Improvement scale 144
Sheehan Disability Scale 144
CHAPTER 6 LATE-STAGE DRUG ANALYSIS AND FORECASTS 146
Key late-stage pipeline summary 148
Comparative forecasts 148
Comparative drug assessment 149
Definition of current comparator therapy 150
Forest/Lundbeck's Lexapro is Datamonitor's comparator therapy 150
Clinical trial data 151
Side-effect profile 152
Forecasted late-stage pipeline drugs 153
Seroquel XR (quetiapine fumarate extended release, Astrazeneca) 153
Drug overview 153
Forecasts to 2017 154
Marketing factors 156
Patient potential 159
Satisfaction of unmet needs 160
Clinical trial data 161
LuAA21004 (Lundbeck, Takeda) 164
Drug overview 164
Forecasts to 2017 165
Marketing factors 167
Patient potential 168
Satisfaction of unmet needs 168
Clinical trial data 169
TIK-101 (Tikvah Therapeutics) 170
Drug overview 170
Forecasts to 2017 171
Marketing factors 172
Patient potential 174
Clinical trial data 175
PD-332334 (Pfizer) 177
Drug overview 177
Forecasts to 2017 177
Marketing factors 180
Patient potential 182
Satisfaction of unmet needs 183
Clinical trial data 183
Unforecasted late-stage drugs 186
Saredutant (SR-48968, Sanofi-Aventis) 186
Drug overview 186
Despite well documented failures of NK receptor antagonists in treating major depressive disorder, this drug class still holds potential in anxiety disorders 186
Completed clinical trials 188
Osemozotan (MN-305, MediciniNova) 189
TGWOOAA (Fabre-Kramer) 190
TGWOOAA's mechanism of action is not particularly unique 190
Efficacy in treating sexual dysfunction will serve as a key product differentiator 190
Fabre-Kramer will need to find a marketing partner 191
ABIO-08-01 (BTG-1640, Abiogen) 191
Casopitant (679769, GlaxoSmithKline) 192
BCI-540 (BrainCells) 193
GW-876008 (Neurocrine, GlaxoSmithKline) 194
GSK-561679 (Neurocrine, GlaxoSmithKline) 195
PH-94B (Pherin) 196
NPL-2003 (Neuropharm) 197
Rufinamide (SYN-111, Synosia) 199
Nepicastat (SYN-117, Synosia Therapeutics) 200
SEP-225441 (Sepracor) 202
LuAA24530 (Takeda, Lundbeck) 203
SPN-805 (Supernus) 204
AZ-002 (alprazolam, Alexza, Symphony Allegro) 204
BIBLIOGRAPHY 206
Journal papers, books, and conference abstracts 206
Websites 221
Datamonitor reports 236
APPENDIX A -MARKET ASSUMPTIONS 237
New product launches 237
Patent expiries 237
Data definitions, limitations and assumptions 240
Standard units 240
Japanese market data 240
Derivation of sales forecasts and pricing trends 240
Indication-specific sales methodology 240
Anxiety-specific sales calculations 240
Diagnosis values for key brands 241
Report methodology 241
APPENDIX B 244
Contributing experts 244
About Datamonitor 244
About Datamonitor Healthcare 245
About the Disease analysis team 246
Disclaimer 247
List of Tables
Table 1: ICD-10 classification codes for anxiety disorders 13
Table 2: DSM-IV classification codes for anxiety disorders 14
Table 3: Prevalence of anxiety disorder subtypes across the seven major markets, 2008 22
Table 4: Prevalence rates of generalized anxiety disorder 23
Table 5: Prevalence of generalized anxiety disorder in the seven major markets, 2008 24
Table 6: Prevalence rates of panic disorder in the seven major markets, 2008 25
Table 7: Prevalence of panic disorder in the seven major markets, 2008 26
Table 8: Prevalence rates of social anxiety disorder 27
Table 9: Prevalence of social anxiety disorder in the seven major markets, 2008 28
Table 10: Prevalence rates of obsessive-compulsive disorder 29
Table 11: Prevalence of obsessive-compulsive disorder in the seven major markets, 2008 30
Table 12: Prevalence rates of post-traumatic stress disorder 31
Table 13: Prevalence of post-traumatic stress disorder (PTSD) in the seven major markets, 2008 32
Table 14: Prevalence rates of agoraphobia across the seven major markets 33
Table 15: Prevalence of agoraphobia in the seven major markets, 2008 34
Table 16: Prevalence rates of specific phobias 35
Table 17: Prevalence of specific phobias in the seven major markets, 2008 36
Table 18: Prevalence of a co-morbid psychiatric condition with anxiety disorders across the seven major markets 41
Table 19: Sales of the top six drugs indicated for anxiety disorders, seven major markets, 2006-07 65
Table 20: Seven major market sales forecast for key branded drugs within the anxiety disorders market ($m), 2007-2017 72
Table 21: Leading branded drug sales revenue ($m) for anxiety disorders in the seven major markets, 2007 and 2017 77
Table 22: Lexapro: key facts, 2008 80
Table 23: Key clinical trials of Lexapro in the treatment of generalized anxiety disorder 84
Table 24: Key clinical trial results of Lexapro in the treatment of panic disorder 85
Table 25: Key clinical trial results of Lexapro in the treatment of social anxiety disorder (SAD) 86
Table 26: Key clinical trials of Lexapro in the treatment of obsessive-compulsive disorder 86
Table 27: Effexor/Effexor XR: key facts, 2008 89
Table 28: Key clinical trials of Effexor XR in the treatment of generalized anxiety disorder 93
Table 29: Key clinical trials of Effexor XR in the treatment of social anxiety disorder 94
Table 30: Key clinical trials of Effexor XR in the treatment of panic disorder 95
Table 31: Cymbalta: key facts, 2008 98
Table 32: Key clinical trials of Cymbalta in the treatment of generalized anxiety disorder 102
Table 33: Paxil/Paxil CR: key facts, 2008 104
Table 34: Key clinical trial results of Paxil CR in the treatment of social anxiety disorder (SAD) 109
Table 35: Key clinical trial results of Paxil CR in the treatment of panic disorder 109
Table 36: Xanax franchise: key facts 111
Table 37: Key clinical trials of Xanax XR in the treatment of panic disorder 116
Table 38: Lyrica: key facts 118
Table 39: Key clinical trials of Lyrica in the treatment of generalized anxiety disorder (GAD) 123
Table 40: Key pipeline drugs in late-stage development for anxiety disorders, 2008 127
Table 41: Drugs in early-stage development for anxiety disorders, 2008 129
Table 42: Number of key anxiolytics by class and Phase of development, 2008 131
Table 43: Forecasted late stage pipeline drugs, 2008 148
Table 44: Lexapro: key clinical trial results 151
Table 45: Factors impacting on the revenues of Seroquel XR, 2008-2017 155
Table 46: Factors impacting on the revenues of LuAA21004, 2008-2017 166
Table 47: Phase III trials of LuAA21004 in generalized anxiety disorder, 2008 169
Table 48: Factors impacting the revenues of TIK-101, 2008-2017 171
Table 49: Factors impacting on the revenues of PD-332334, 2008-2017 178
Table 50: Pfizer's anxiety disorders portfolio, 2008 180
Table 51: Phase III trials of PD-332334 generalized anxiety disorder, 2008 185
Table 52: Phase III trials of saredutant in generalized anxiety disorder 188
Table 53: Key facts: Phase II trial of casopitant in social anxiety disorder 192
Table 54: Key facts: Phase II trial of BCI-540 in depression and anxiety 194
Table 55: Key facts: Phase II trial of NLP-2003 in obsessive-compulsive disorder 198
Table 56: Key facts: Phase II trial of rufinamide in generalized anxiety disorder 199
Table 57: Key facts: Phase II trial of nepicastat in post-traumatic stress disorder 201
Table 58: Key facts: Second Phase II trial of nepicastat in post-traumatic stress disorder 201
Table 59: Key facts: Phase II trial of SEP-225441 in generalized anxiety disorder 202
Table 60: Datamonitor's launch dates for anxiety disorder products across the US, 5EU and Japan, 2008-2017 237
Table 61: Patent expiries of key branded anxiolytics across the US, the 5EU and Japan 237
Table 62: Patent expiries of key branded drugs prescribed off-label for anxiety disorders across the US, the 5EU and Japan 238
Table 63: Anxiety diagnosis values (%) for key brands sales ($) in the US, 2005-07 241
Table 64: Datamonitor drug assessment parameters 243
List of Figures
Figure 1: Datamonitor drug competitive positioning analysis of pipeline drugs in development for anxiety disorders in the seven major markets over the forecast period, 2008-2017 8
Figure 2: Historical (2004-2007) and forecast (2008-2017) anxiety-specific sales revenue for key marketed and pipeline drugs across the 7MM 9
Figure 3: Prevalence of anxiety disorder subtypes across the seven major markets, 2008 21
Figure 4: Patient distribution: acute versus chronic anxiety 37
Figure 5: Key unmet needs in the treatment of anxiety disorders, 2008 43
Figure 6: Value ($) and volume (SU) sales of anxiety disorder therapies across the seven major markets, 2004-07 61
Figure 7: Key events affecting the anxiety disorders market, 2004-08 62
Figure 8: Anxiety disorder-specific sales by country in the seven major markets, 2006-07 63
Figure 9: Share of key drug classes used to treat anxiety disorders in the seven major market, 2007 65
Figure 10: Seven major market sales revenue of the leading branded anxiety disorder drugs, 2004-07 66
Figure 11: Total non-direct to consumer promotional spend of key brands, 2005-2007 68
Figure 12: Seven major market anxiety disorder sales revenue by indication, 2007 70
Figure 13: Anxiety disorder-specific sales revenue across the US, Japan and 5EU, ($m), 2004-2017 71
Figure 14: Key events impacting the anxiety disorders market, 2008-2017 74
Figure 15: Lexapro (escitalopram)- clinical and commercial attractiveness, 2008 76
Figure 16: Key marketed drugs approved for specific anxiety disorders in the US, 5EU and Japan, 2008 78
Figure 17: Lexapro: proportion of branded anxiety disorder sales across the seven major markets, 2004-07 81
Figure 18: Lexapro anxiety-specific sales revenue ($m) across the seven major markets, 2004-07 historical, 2008-2017 forecasts 82
Figure 19: Lexapro (escitalopram): SWOT analysis for the anxiety disorders market, 2008 83
Figure 20: Effexor/Effexor XR: proportion of branded anxiety disorder sales across the seven major markets, 2004-07 90
Figure 21: Effexor/Effexor XR anxiety-specific sales revenue ($m) across the seven major markets, 2004-07 historical, 2008-2017 forecasts 91
Figure 22: Effexor XR(venlafaxine extended release): SWOT analysis for the anxiety disorders market, 2008 92
Figure 23: Cymbalta: proportion of branded anxiety disorder sales across the seven major markets, 2004-07 99
Figure 24: Cymbalta anxiety-specific sales revenue ($m) across the seven major markets, 2004-07 historical, 2008-2017 forecasts 100
Figure 25: Cymbalta (duloxtine): SWOT analysis for the anxiety disorders market, 2008 101
Figure 26: Paxil/Paxil CR: proportion of branded anxiety disorder sales across the seven major markets, 2004-07 106
Figure 27: Paxil franchise anxiety-specific sales revenue ($m) across the seven major markets, 2004-07 historical, 2008-2017 forecasts 107
Figure 28: Paxil CR (paroxetine controlled release): SWOT analysis for the anxiety disorders market, 2008 108
Figure 29: Xanax/Xanax XR: proportion of branded anxiety disorder sales across the seven major markets, 2004-07 112
Figure 30: Xanax franchise anxiety-specific sales ($m) across the seven major markets, 2004-07 historical, 2008-17 forecasts 113
Figure 31: Xanax XR (alprazolam extended release): SWOT analysis for the anxiety disorders market, 2008 114
Figure 32: Lyrica anxiety-specific sales ($m) across the seven major markets, 2004-07 historical, 2008-17 forecasts 120
Figure 33: Lyrica (pregabalin): SWOT analysis for the anxiety disorders market, 2008 122
Figure 34: Drugs in development for anxiety disorders by class and development stage, 2008 130
Figure 35: Comparative late-stage pipeline anxiety disorder drug sales revenue forecast, 2008-2017 149
Figure 36: Datamonitor drug assessment summary of pipeline drugs in development for anxiety disorders across the seven major markets, 2008-2017 150
Figure 37: Anxiety-specific sales forecast of Seroquel XR in the seven major markets, 2008-2017 154
Figure 38: Datamonitor's competitive positioning analysis of Seroquel XR in anxiety disorders across the seven major markets, 2008-2017 155
Figure 39: Anxiety specific sales ($m) in the seven major markets of Seroquel/Seroquel XR and key drugs approved for anxiety disorders, 2004-07 156
Figure 40: Anxiety-specific sales forecast of LuAA21004 in the seven major markets, 2007-2017 165
Figure 41: Datamonitor's competitive positioning analysis of LuAA21004 in anxiety disorders across the seven major markets, 2008-2017 166
Figure 42: Anxiety-specific sales forecast of TIK-101 in the seven major markets, 2008-2017 171
Figure 43: Datamonitor's competitive positioning analysis of TIK-101 in anxiety disorders across the seven major markets, 2008-2017 172
Figure 44: Anxiety-specific sales forecast of PD-332334 in the seven major markets, 2008-2017 178
Figure 45: Datamonitor's competitive positioning analysis of PD-332334 in anxiety disorders across the seven major markets, 2008-2017 179
Figure 46: Phase II results: PD-332334 in generalized anxiety disorder 184