Bipolar Disorder - New treatments for bipolar depression set to drive near-term growth
ABOUT DATAMONITOR HEALTHCARE 2
About the CNS pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the bipolar disorder market 4
Summary 6
Datamonitor Pipeline Assessment Summary 8
CHAPTER 2 PATIENT POTENTIAL 22
Definition of bipolar disorder 23
Characteristics of bipolar disorder phases 23
Segmentation of bipolar disorder subtypes 24
Bipolar I disorder 25
Bipolar II disorder 25
Bipolar III disorder (cyclothymia) 25
Epidemiology of bipolar disorder 27
Prevalence and diagnosis rate of bipolar disorder 27
Increased prevalence rate due to relaxing of inclusion criteria 27
Poor correct diagnosis rates leave room for market expansion 27
Unmet needs in bipolar disorder 29
Unmet need 1: improved maintenance therapy 29
Improved prophylactic treatment the key to real patient benefit 29
Unmet need 2: bipolar depression 30
Sufferers spend significantly longer in bipolar depression than mania 30
High suicide rate during depressive phase 30
Traditional antidepressants have limited efficacy 31
Unmet need 3: treatment non-compliance 32
Unmet need 4: side effects 32
Unmet need 5: onset of therapeutic action 32
Etiology of bipolar disorder 33
Neurobiology of bipolar disorder 33
Dopamine hypothesis of schizophrenia and bipolar mania 34
Monoamine theory of major depression and bipolar depression 35
CHAPTER 3 R&D APPROACH 37
Market overview 38
Current treatment paradigms for bipolar disorder 38
Treatment of manic episodes associated with bipolar disorder 38
Maintenance and prophylactic therapy 38
Treatment of bipolar depression 39
Sales of antipsychotics generated approximately half the revenues associated
with bipolar disorder pharmacotherapy 39
Off-label use of antidepressants for bipolar disorder treatment 40
Classification of pipeline drugs seeking indication in bipolar disorder 42
Novel mood stabilizers 42
Anticonvulsants 43
Antipsychotics 44
Pharmacological development of antipsychotics 44
Mixed molecular targets of the current and pipeline atypical antipsychotics 45
Increasing concentration on side-effect profile for the antipsychotic class of
therapy 46
Clinical trial design in bipolar disorder 47
Young mania rating scale 47
Montgomery-Åsberg Depression Rating Scale 47
Hamilton Rating Scale for Depression 48
Positive and Negative Syndrome Scale 48
Problems associated with bipolar disorder clinical trial design 48
Pipeline overview 49
Pipeline drugs in pre-registration 49
Pipeline drugs in Phase III clinical development 50
Pipeline drugs in Phase II clinical development 51
Pipeline drugs in Phase I clinical development 51
Lack of innovative and Phase I drugs found in the bipolar disorder pipeline 52
Key companies involved in the bipolar disorder pipeline 53
Johnson & Johnson's bipolar disorder franchise will decline from 2008 onwards
despite the launch of paliperidone 53
Generic incursion expected when key CNS products come off-patent 53
Follow-on antipsychotic may not be sufficiently differentiated 53
Off-label bipolar-specific sales of topiramate may deteriorate following
negative trial results 54
RepliGen are developing a novel intracellular mood stabilizer 54
RG-2417 (Uridine) a potential novel mood stabilizer 55
Previous failure to show statistically significant efficacy of secretin in
schizophrenia 55
Phase I trial with RG-2133-another Uridine pro-drug 56
CHAPTER 4 ANTIPSYCHOTIC LATE-STAGE DRUG ANALYSIS & FORECASTS 58
Overview of antipsychotic class of bipolar therapy 59
Pipeline summary 59
Definition of current comparator therapy 59
US market leader status for Seroquel despite not being licensed for maintenance
therapy 62
Sales of atypical antipsychotics are higher for bipolar disorder than
schizophrenia in the US 63
Short to medium-term sales unaffected by indication expansion 64
Experience from prescribing for schizophrenia drove the bipolar atypical
antipsychotic market 67
Indication expansion may not be financially beneficial unless the right bipolar
indication is sought 67
Factors required for a pipeline antipsychotic to compete in the bipolar disorder
market 69
Market sales and forecast caveats 70
Seroquel for bipolar depression 71
Profile 71
Drug overview: indication expansion into bipolar depression imminent 71
Clinical trial data 72
Clinical trial data and pharmacodynamic summary 74
Why would an atypical antipsychotic have therapeutic efficacy against bipolar
depression? 75
Patient potential 79
Marketing factors 80
Satisfaction of unmet needs 82
Unmet need 1: improved maintenance therapy 82
Unmet need 2: bipolar depression 82
Unmet need 3: treatment non-compliance 82
Unmet need 4: side effects 83
Unmet need 5: onset of therapeutic action 83
Forecasts to 2015 84
Brief explanation of impacting factors 85
Datamonitor drug assessment summary 86
Geodon for bipolar depression 87
Profile 87
Drug overview: indication expansion into bipolar depression 87
Clinical trial data 87
Clinical trial data and pharmacokinetic summary 90
Patient potential 90
Marketing factors 90
Satisfaction of unmet needs 91
Unmet need 1: improved maintenance therapy 91
Unmet need 2: bipolar depression 91
Unmet need 3: treatment non-compliance 91
Unmet need 4: side effects 91
Unmet need 5: onset of therapeutic action 92
Forecasts to 2015 92
Brief explanation of impacting factors 93
Datamonitor drug assessment summary 94
Risperdal Consta 95
Profile 95
Drug overview: intramuscular sustained-release formulation of Risperdal 95
Clinical trial data 95
Clinical trial data and pharmacokinetic summary 97
Patient potential 97
Significant off-label usage reduces the "new" patient population 97
Risperdal Consta will be competing with the oral formulations rather than IM
formulations 99
Marketing factors 100
Price is primary concern but sales revenue looks strong 100
Increased use of risperidone might have a positive effect on Risperdal Consta
sales 101
J&J should target its marketing of Risperdal Consta towards treating severely
manic patients 102
Satisfaction of unmet needs 103
Unmet need 1: improved maintenance therapy 103
Unmet need 2: bipolar depression 103
Unmet need 3: treatment non-compliance 103
Unmet need 4: side effects 104
Unmet need 5: onset of therapeutic action 104
Forecast to 2015 105
Brief explanation of impacting factors 106
Datamonitor drug assessment summary 107
Intramuscular Abilify 108
Profile 108
Drug overview: intramuscular version of Abilify for acute intervention 108
Clinical trial data 108
Clinical trial data and pharmacokinetic summary 111
Patient potential 112
IM version may boost sales of oral Abilify as a first-line therapy 112
Abilify needs to demonstrate strong efficacy in a head-to-head study 113
Abilify's positive side-effect profile may not be a significant advantage in the
acute setting 114
Abilify's lack of sedation may prove to be a disadvantage for acute mania
treatment 115
Marketing factors 116
How will Abilify IM be priced? 116
BMS/Otsuka should consider a long-acting IM version of Abilify 118
Satisfaction of unmet needs 119
Unmet need 1: improved maintenance therapy 119
Unmet need 2: bipolar depression 119
Unmet need 3: treatment non-compliance 119
Unmet need 4: side effects 119
Unmet need 5: onset of therapeutic action 119
Forecast to 2015 120
Brief explanation of impacting factors 121
Datamonitor drug assessment summary 122
Asenapine 123
Profile 123
Drug overview: "new" atypical antipsychotic 123
Clinical trial data 123
Clinical trial data and pharmacokinetic summary 125
Patient potential 128
Marketing factors 128
Pfizer bring a wealth of experience in marketing atypical antipsychotics to the
table 128
Establishing a niche patient population for asenapine will be important for its
commercial success in bipolar disorder 129
Delay in development may impact future sales estimates 130
Satisfaction of unmet needs 130
Unmet need 1: improved maintenance therapy 130
Unmet need 2: bipolar depression 130
Unmet need 3: treatment non-compliance 130
Unmet need 4: side-effects 131
Unmet need 5: onset of therapeutic action 132
Forecast to 2015 133
Brief explanation of impacting factors 134
Datamonitor drug assessment summary 135
Bifeprunox 136
Profile 136
Drug overview: New atypical antipsychotic with similar mode of action to Abilify
136
Clinical trial data 136
Clinical trial data and pharmacokinetic summary 139
Patient potential 140
Bifeprunox unlikely to be used for acute mania, but may have a niche in
first-line maintenance therapy 140
Marketing factors 142
Solvay's and Wyeth's experience in psychiatry and Lundbeck's launch of
sertindole will provide a strong base for the commercialization of bifeprunox
142
Differentiation from Abilify may become a problem 142
Indication in bipolar depression could boost sales and save time/money 143
Key events which could impact the revenue growth of bifeprunox 143
Satisfaction of unmet needs 143
Unmet need 1: improved maintenance therapy 143
Unmet need 2: bipolar depression 144
Unmet need 3: treatment non-compliance 144
Unmet need 4: side effects 144
Unmet need 5: onset of therapeutic action 144
Forecast to 2015 145
Brief explanation of impacting factors 146
Datamonitor drug assessment summary 147
Paliperidone ER 148
Profile 148
Drug overview: metabolite of risperidone 148
Clinical trial data 148
Clinical trial data and pharmacokinetic summary 150
Patient potential 150
Development of paliperidone IM for bipolar disorder could be a better strategy
151
Marketing factors 153
Are active metabolites commercially viable? 153
Following Risperdal patent expiry-making the switch to paliperidone versus
generic risperidone 154
Satisfaction of unmet needs 157
Unmet need 1: improved maintenance therapy 157
Unmet need 2: bipolar depression 157
Unmet need 3: treatment non-compliance 157
Unmet need 4: side effects 157
Unmet need 5: onset of therapeutic action 158
Forecast to 2015 159
Brief explanation of impacting factors 160
Datamonitor drug assessment summary 161
CHAPTER 5 ANTICONVULSANT LATE-STAGE DRUG ANALYSIS & FORECASTS 162
Overview for anticonvulsants 163
Pipeline summary 163
Definition of current comparator therapy 163
Anticonvulsant 'gold-standard': lamotrigine 163
Licarbazepine 167
Profile 167
Drug overview: Metabolite of the anticonvulsant oxcarbazepine 167
Clinical trial data 167
Patient potential 173
Marketing factors 173
Satisfaction of unmet needs 174
Unmet need 1: improved maintenance therapy 174
Unmet need 2: bipolar depression 175
Unmet need 3: treatment non-compliance 175
Unmet need 4: side effects 175
Unmet need 5: onset of therapeutic action 175
Forecast to 2015 176
Brief explanation of impacting factors 176
CHAPTER 6 NOVEL MOOD STABILIZER LATE-STAGE DRUG ANALYSIS & FORECAST 178
Overview for novel mood stabilizers 179
Pipeline summary 179
Definition of current comparator therapy 179
Mood stabilizer 'gold-standard': lithium 179
RG-2417 (Uridine) 180
Profile 180
Drug overview: Novel metabolism modulator 180
Clinical trial data 180
Patient potential 182
Marketing factors 182
Satisfaction of unmet needs 182
Forecast to 2015 182
Memantine 183
Profile 183
Drug overview: NMDA receptor antagonist 183
Clinical trial data 183
Patient potential 185
Marketing factors 185
Satisfaction of unmet needs 185