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