Pipeline Insight: Depression - Novel drugs to grow third-line market
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Scope of the analysis - page 3
- Datamonitor insight into the depression market - page 5
- Summary - page 5
- Key metrics - page 6
- Datamonitor Pipeline Assessment Summary - page 7
- CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS - page 23
- Pipeline overview - page 24
- Pipeline drugs in pre-registration and registration - page 25
- Pipeline drugs in Phase III clinical development - page 26
- Pipeline drugs in Phase II clinical development - page 27
- Discontinued and suspended projects - page 28
- CP-316311 and CP-122721 - page 28
- Aprepitant and L-759274 - page 28
- Dilopetine - page 28
- MN-305 - page 28
- OPC-14523 - page 29
- Radafaxine - page 29
- Key companies involved in the depression pipeline - page 29
- GSK - page 29
- Paxil - page 30
- Wellbutrin - page 30
- GSK will hope that pipeline drugs fill the gap left by Paxil's decline - page 31
- Sanofi-Aventis - page 32
- GSK - page 29
- Key R&D company strategies - page 33
- Reformulation strategies - page 33
- Drug delivery reformulations - page 33
- Chemical reformulation - page 35
- Secondary indications - page 36
- Reformulation strategies - page 33
- Datamonitor's gold standard MDD drug - page 37
- Paxil chosen due to its frequent incorporation into clinical trial designs - page 37
- Pipeline overview - page 24
- CHAPTER 3 DEPRESSION - MARKET POTENTIAL - page 39
- Definition of depression - page 40
- DSM-IV - page 40
- ICD-10 - page 41
- Segmentation of MDD - page 42
- Elderly MDD - page 42
- Child and adolescent MDD - page 43
- Epidemiology of depression - page 45
- MDD prevalence in the major markets - page 45
- 12-month prevalence rate of 6.6% in the US - page 45
- 12-month prevalence rate of 6.7% across Europe - page 46
- Substantially lower prevalence rate in Japan than in the US or Europe - page 46
- Age group variance in MDD prevalence rate - page 46
- Diagnosis and treatment - page 46
- Current classes used in depression treatment - page 47
- MAOIs and TCAs-effective but side effects and safety are a concern - page 47
- SSRIs retain the efficacy of MAOIs and TCAs but with more favorable side-effect and safety profiles - page 49
- SNRIs have added to the treatment options, but are generally not used first-line - page 50
- Treatment algorithms for MDD - page 51
- Co-morbid disorders - page 52
- More than half of MDD sufferers also suffer from anxiety - page 52
- MDD prevalence in the major markets - page 45
- Unmet needs in depression - page 54
- Faster onset of action - page 55
- Side effects - page 56
- Patient compliance - page 57
- Efficacy - page 57
- Efficacy may be low for first monotherapy, but improves at second-line - page 57
- Efficacy similar between currently available antidepressants - page 58
- Better combinations - page 59
- Definition of depression - page 40
- CHAPTER 4 R&D APPROACH - page 60
- Classification of pipeline products - page 61
- Datamonitor's classification of pipeline products - page 61
- SNRIs - page 61
- Triple reuptake inhibitors - page 61
- NK receptor antagonists - page 61
- Serotonin receptor ligands - page 62
- Other therapies - page 63
- Datamonitor's classification of pipeline products - page 61
- Clinical trial design in depression - page 63
- Patient population - page 63
- Placebo effect - page 63
- Clinical trial endpoints in depression - page 64
- Hamilton Rating Scale for Depression - page 64
- Hamilton Rating Scale for Anxiety - page 65
- Montgomery-Asberg Depression Rating Scale - page 65
- Clinical Global Impression Scale - page 65
- The Beck Depression Rating Scale - page 66
- The Zung Self-Rating Depression Scale - page 66
- Brief Psychiatric Rating Scale - page 66
- Classification of pipeline products - page 61
- CHAPTER 5 SEROTONIN NOREPINEPHRINE REUPTAKE INHIBITORS LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 67
- Overview for SNRIs - page 68
- Pipeline summary - page 68
- Definition of current comparator therapy - page 68
- Effexor XR (venlafaxine extended release) - page 68
- Desvenlafaxine (Pristiq) - page 70
- Profile - page 70
- Drug overview: metabolite of the blockbuster Effexor - page 70
- Clinical trial data - page 71
- Efficacy and safety of Pristiq in the treatment of MDD - page 71
- Randomized, double-blind, placebo-controlled study of desvenlafaxine succinate in MDD - page 72
- Adverse events in the two desvenlafaxine Phase III studies - page 73
- Double-blind, placebo- and moxifloxacin-controlled crossover study of the effects of desvenlafaxine succinate on QT interval in healthy adult female subjects - page 73
- Ongoing clinical trials investigating the efficacy of desvenlafaxine as a treatment of MDD - page 74
- Preclinical - page 74
- Patient potential - page 75
- Marketing factors - page 78
- Satisfaction of unmet needs - page 80
- Forecasts to 2016 - page 81
- Generic Effexor XR launch - page 82
- Switching from Effexor XR to Pristiq in the estimated two years before the launch of generics - page 83
- Datamonitor drug assessment summary - page 84
- Profile - page 70
- Overview for SNRIs - page 68
- CHAPTER 6 TRIPLE REUPTAKE INHIBITORS (SEROTONIN/NOREPINEPHRINE/DOPAMINE) LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 85
- Overview for triple reuptake inhibitors - page 86
- Pipeline summary - page 86
- Triple reuptake inhibitors are designed to inhibit the reuptake of serotonin, norepinephrine and dopamine - page 86
- Studies investigating triple reuptake inhibition with two separate compounds - page 87
- Definition of current comparator therapy - page 88
- Effexor XR - page 88
- DOV-216 303 - page 88
- Profile - page 88
- Drug overview : DOV-216,303 has a complicated licensing history - page 88
- Clinical trial data - page 88
- Phase II clinical trial - page 89
- Phase 1b clinical trial - page 89
- Phase 1a clinical trial - page 90
- Preclinical studies - page 91
- Datamonitor comments - page 91
- Profile - page 88
- NS-2359 (GSK372475) - page 94
- Profile - page 94
- Drug overview: triple reuptake inhibitor under development by GSK - page 94
- Ongoing clinical trials - page 95
- Datamonitor comments - page 95
- Profile - page 94
- Overview for triple reuptake inhibitors - page 86
- CHAPTER 7 NK RECEPTOR ANTAGONISTS LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 96
- Overview for NK receptor antagonists - page 97
- Pipeline summary - page 97
- Lack of efficacy of the NK1 receptor antagonist aprepitant in the treatment of MDD - page 97
- Definition of current comparator therapy - page 99
- Saredutant - page 99
- Profile - page 99
- Drug overview: NK2 receptor antagonist - page 99
- Clinical trials data - page 99
- Phase IIb clinical trial data - page 99
- Preclinical data - page 100
- Ongoing clinical trial program for saredutant in MDD - page 101
- Patient potential - page 102
- Room for an alternative mode of action in the depression market - page 102
- Possible indication expansion into anxiety and pain - page 102
- Marketing factors - page 103
- Sanofi-Aventis has a broad experience of marketing drugs to psychiatrists - page 103
- Satisfaction of unmet needs - page 104
- Speed of onset of action - page 104
- Side effects - page 104
- Patient compliance - page 105
- Better combinations - page 105
- Forecasts to 2016 - page 106
- Saredutant could gain market share from current third-line therapies - page 107
- Datamonitor drug assessment summary - page 108
- Profile - page 99
- Other NK receptor modulators in development - page 109
- Casopitant - page 109
- Vestipitant + paroxetine - page 109
- Overview for NK receptor antagonists - page 97
- CHAPTER 8 SEROTONIN RECEPTOR LIGANDS LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 110
- Overview for serotonin receptor ligands - page 111
- Pipeline summary - page 111
- Definition of current comparator therapy - page 111
- Gepirone ER - page 111
- Profile - page 111
- Drug overview: resubmission likely six years following original submission - page 111
- Regulatory submissions - page 112
- Clinical trial data - page 113
- Relapse prevention with gepirone ER in outpatients with MDD - page 113
- Retrospective subgroup analysis in patients with MDD - page 114
- Sustained efficacy of gepirone-IR in MDD: a double-blind placebo substitution trial - page 115
- Relapse prevention with gepirone ER in outpatients with MDD - page 116
- Effect of gepirone ER on sexual function in patients with MDD - page 117
- Gepirone ER in patients with anxious depression - page 118
- Effects of gepirone ER on depression with anxiety symptoms: a double-blind, placebo-controlled study - page 118
- Gepirone ER: new evidence for efficacy in the treatment of MDD - page 119
- Phase II relapse prevention during long-term gepirone IR therapy for MDD: a double-blind substitution trial - page 120
- Patient potential - page 121
- Marketing factors - page 122
- Satisfaction of unmet needs - page 123
- Faster onset of action - page 123
- Side effects - page 123
- Patient compliance - page 124
- Efficacy - page 124
- Better combinations - page 124
- Forecasts to 2016 - page 125
- Gepirone ER will gain market share from third-line therapies in the US and EU - page 126
- Datamonitor drug assessment summary - page 128
- Profile - page 111
- Quetiapine (Seroquel SR) - page 129
- Profile - page 129
- Drug overview: atypical antipsychotic - page 129
- Clinical trial data - page 130
- BOLDER I-A randomized, double-blind, placebo-controlled trial of Seroquel (quetiapine) in the treatment of bipolar I or II depression. - page 130
- BOLDER II-Efficacy of Seroquel (quetiapine) monotherapy in bipolar depression: A confirmatory double-blind, placebo-controlled study - page 131
- Ongoing clinical trial program for Seroquel SR in MDD - page 132
- Current state of development - page 132
- Profile - page 129
- Vilazodone - page 134
- Profile - page 134
- Drug overview: targeting niche sub-population of MDD sufferers - page 134
- Genetically guided antidepressant - page 135
- Clinical trial data - page 135
- Phase III program - page 135
- Preclinical - page 135
- Ongoing clinical trial program - page 136
- Current state of development - page 136
- Profile - page 134
- Other Serotonin receptor ligands - page 137
- Elzasonan - page 137
- F-2695 - page 137
- Overview for serotonin receptor ligands - page 111
- CHAPTER 9 OTHER THERAPIES LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 138
- Overview for other therapies - page 139
- Pipeline summary - page 139
- Definition of current comparator therapy - page 140
- Agomelatine - page 140
- Profile - page 140
- Drug overview: the first melatonergic antidepressant - page 140
- Failed European submission by Servier - page 140
- US filing by Novartis - page 141
- Clinical trial data - page 141
- Placebo-controlled trial of agomelatine in the treatment of MDD presented at the 13th Congress of the Association of European Psychiatrists (April 2005). - page 141
- Placebo-controlled trial of agomelatine in the treatment of MDD - page 142
- Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with Paxil: a randomized, double-blind, placebo-controlled discontinuation study. - page 143
- Double-blind pilot study comparing the therapeutic effect of two doses of agomelatine in the treatment of MDD - page 144
- Determination of the dose of agomelatine, a melatonergic agonist and selective 5-HT2C antagonist, in the treatment of MDD: a placebo-controlled dose range study. - page 145
- Melatonin and agomelatine increase REM sleep and wake-up propensity without modifying NREM sleep homeostasis. - page 146
- Ongoing clinical trials - page 146
- Patient potential - page 147
- Marketing factors - page 149
- Satisfaction of unmet needs - page 149
- Faster onset of action - page 149
- Side effects - page 150
- Patient compliance - page 150
- Efficacy - page 150
- Better combinations - page 150
- Forecasts to 2016 - page 151
- Significant market share gained from hypnotics currently prescribed for depression - page 152
- Datamonitor drug assessment summary - page 153
- Profile - page 140
- Nemifitide - page 154
- Profile - page 154
- Clinical trial data - page 154
- Double-blind, placebo-controlled study of nemifitide in the treatment of outpatients with MDD - page 154
- Phase IIc open-label extension study - page 155
- Phase IIa - A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of nemifitide, a novel antidepressant peptide, in the treatment of major depression - page 156
- Clinical pharmacokinetic studies with INN 00835 (nemifitide), a novel pentapeptide antidepressant - page 157
- Preclinical - page 158
- Patient potential - page 159
- Marketing factors - page 160
- Satisfaction of unmet needs - page 161
- Faster onset of action - page 161
- Side effects - page 161
- Patients compliance - page 161
- Efficacy - page 161
- Better combinations - page 162
- Forecasts to 2016 - page 162
- Uptake is slow and market share gain limited due to route of administration - page 163
- Datamonitor drug assessment summary - page 164
- Corlux (mifepristone) - page 165
- Profile - page 165
- Drug overview: specifically targeting psychotic depression - page 165
- Clinical trial data - page 166
- Corcept 09 - page 166
- Corcept 07 - page 166
- Corcept 03 - Mifepristone versus placebo in the treatment of psychosis in patients with psychotic major depression - page 167
- Corcept 02 - Clinical and biological effects of mifepristone treatment for psychotic depression - page 168
- An eight-week open-label trial of a six-day course of mifepristone for the treatment of psychotic depression - page 168
- An open-label trial of C-1073 (mifepristone) for psychotic major depression - page 169
- Rapid reversal of psychotic depression using mifepristone - page 170
- Ongoing clinical trial program for mifepristone in MDD - page 170
- Profile - page 165
- Amibegron - page 172
- Profile - page 172
- Drug overview: beta-3 adrenergic receptor agonist - page 172
- Clinical trial data - page 172
- Phase III European study in patients with a recurrent major depressive episode (EFC 5374) - page 172
- EFC 5379 - Non-conclusive result from North American study - page 174
- Ongoing clinical trial program for amibegron in MDD - page 174
- Profile - page 172
- Other novel therapies in clinical development - page 176
- Miraxion (LAX-101) - page 176
- BMS-562086 - page 176
- TRIDMAC - page 177
- Clinical trial data - page 177
- Org 24448 - page 178
- Org 34517 - page 179
- Ongoing clinical trials - page 180
- SSR149415 - page 180
- Ongoing clinical trials - page 181
- YKP10A - page 181
- Phase II study - page 181
- Phase I - page 182
- Overview for other therapies - page 139
- CHAPTER 10 INNOVATIVE EARLY-STAGE PROJECTS - page 183
- Key Phase I and preclinical compounds in MDD - page 184
- Key Phase I compounds in depression - page 185
- TC-2216 - page 185
- How are NNRs and depression linked? - page 185
- Preclinical and clinical development of TC-2216 - page 186
- SEP-225289 - page 187
- TC-2216 - page 185
- BIBLIOGRAPHY - page 189
- Journals - page 189
- Websites - page 197
- APPENDIX A - page 201
- Methodology - page 201
- Datamonitor forecast methodology - page 201
- ICD-10 codes used to define current depression market - page 201
- Estimated 2006 sales revenue - page 202
- MDD specific sales calculations - page 202
- Product forecasts - page 202
- Definition of a standard unit - page 202
- Japanese market data - page 203
- Datamonitor drug assessment summary - page 203
- Datamonitor forecast methodology - page 201
- Report methodology - page 203
- Methodology - page 201
- APPENDIX B - page 204
- About Datamonitor - page 204
- About Datamonitor Healthcare - page 204
- Datamonitor Healthcare's therapy area capabilities - page 205
- Disclaimer - page 206
- About Datamonitor - page 204
- List of Tables
- Table 1: Datamonitor's forecast MDD revenues of key pipeline drugs and the total MDD market across the seven major markets ($m), 2008-2016 - page 6
- Table 2: Key pipeline drugs in registration and pre-registration for MDD in the seven major markets, 2007 - page 25
- Table 3: Key pipeline drugs in Phase III development for MDD in the seven major markets, 2007 - page 26
- Table 4: Key pipeline drugs in Phase II development for MDD, 2007 - page 27
- Table 5: Prevalence rate and population size for MDD across the seven major markets, 2007 - page 45
- Figure 6: Non-cost related unmet needs in MDD, 2007 - page 54
- Table 6: Key SNRI class drugs in the late-stage MDD R&D pipeline, 2007 - page 68
- Table 7: Estimated key events, approvals and launch dates impacting Pristiq's revenue forecast, 2006-2016 - page 82
- Table 8: Key triple reuptake inhibitor class drugs in the late-stage MDD R&D pipeline, 2007 - page 86
- Table 9: Key NK receptor antagonist class drugs in the late-stage MDD R&D pipeline, 2007 - page 97
- Table 10: Estimated key events, approvals and launch dates impacting saredutant's revenue forecast, 2006-2016 - page 107
- Table 11: Key serotonin receptor ligands class drugs in the late-stage MDD R&D pipeline, 2007 - page 111
- Table 12: Estimated key events, approvals and launch dates impacting gepirone ER's revenue forecast, 2006-2016 - page 126
- Table 13: Key other therapies class drugs in the late-stage MDD R&D pipeline, 2007 - page 139
- Table 14: Estimated key events, approvals and launch dates impacting agomelatine's revenue forecast, 2006-2016 - page 152
- Table 15: Estimated key events, approvals and launch dates impacting nemifitide's revenue forecast, 2006-2016 - page 163
- Table 16: Key pipeline drugs in Phase I development for MDD, 2007 - page 184
- Table 17: Key pipeline drugs in preclinical development for MDD, 2007 - page 185
- Table 18: Possible roles of neuronal nicotinic receptors - page 187
- Table 19: ICD-10 and DSM-IV codes for MDD - page 201
- List of Figures
- Figure 1: Datamonitor's MDD drug assessment summary - page 7
- Figure 2: Drugs in development at each stage of development for MDD, 2007 - page 24
- Figure 3: $1.8 billion decrease in GSK's global depression portfolio between 2003 and 2006. - page 31
- Figure 4: Company reported, all-indication global sales revenue for Prozac, 2000-05 - page 34
- Figure 5: STAR*D treatment algorithm for depression - page 52
- Figure 7: Effexor (venlafaxine) versus SSRIs - page 69
- Figure 8: Datamonitor's forecast of MDD specific sales for Pristiq across the seven major markets ($m), 2006-2016 - page 81
- Figure 9: Datamonitor's competitive positioning analysis for Pristiq in MDD - page 84
- Figure 10: Datamonitor's forecast of MDD specific sales for saredutant across the seven major markets ($m), 2006-2016 - page 106
- Figure 11: Datamonitor's competitive positioning analysis for saredutant in MDD - page 108
- Figure 12: Datamonitor's forecast of MDD specific sales for gepirone ER across the seven major markets ($m), 2006-2016 - page 125
- Figure 13: Datamonitor's competitive positioning analysis for gepirone in MDD - page 128
- Figure 14: Dose adjustment of Seroquel for different indications. - page 130
- Figure 15: Datamonitor's forecast of MDD specific sales for agomelatine across the seven major markets ($m), 2006-2016 - page 151
- Figure 16: Datamonitor's competitive positioning analysis for agomelatine in MDD - page 153
- Figure 17: Datamonitor's forecast of MDD specific sales for nemifitide across the seven major markets ($m), 2006-2016 - page 162
- Figure 18: Datamonitor's competitive positioning analysis for nemifitide in MDD - page 164
- Figure 19: Clinical trial path for amibegron MDD trial (EFC5374) - page 173
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