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

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

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