Pipeline Insight: Schizophrenia - Asenapine; a future market leader?

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 schizophrenia market 5
Key metrics 7
CHAPTER 2 PATIENT POTENTIAL 21
Etiology of schizophrenia 21
DSM-IV defined symptoms of schizophrenia 22
A - Characteristic symptoms 22
B - Social/occupational dysfunction 23
C - Duration 23
D - Schizoaffective and mood disorder exclusion 23
E - Substance/general medical condition exclusion 23
F - Relationship to a pervasive developmental disorder 24
Classification of schizophrenia 24
Epidemiology of schizophrenia 25
Schizophrenia affects 1% of the population 25
Comorbidities of schizophrenia 25
Anxiety is the most prevalent comorbidity of schizophrenia 26
Substance and alcohol abuse is frequently observed in schizophrenia 28
Depression affects a third of schizophrenia patients 28
Diagnosis rates of schizophrenia 30
Unmet needs in schizophrenia 31
Improving patient compliance is key 31
Lack of insight into schizophrenia, and the management thereof, are the most frequent reasons for patient noncompliance 36
Increased public and physician awareness and education 36
The importance of identifying a market niche before launch 39
Greater efficacy with fewer side-effects 40
A need for drugs targeting negative and cognitive symptoms, and partial-responders 41
Long-acting depots and patch technology are favored to improve patient compliance 43
CHAPTER 3 R&D APPROACH 47
Classification of marketed and pipeline products 47
Serotonergic and dopaminergic receptor antipsychotics 48
Dopaminergic antipsychotics 49
Dopamine antagonists 49
Dopamine agonists 49
Serotonergic antipsychotics 50
Serotonin antagonists 50
Serotonin agonists 51
Novel antipsychotics 52
Alpha 2 adrenoceptor antagonists 53
Glutamate (AMPA and NMDA) and glycine receptor modulators 53
Cannabinoids 54
Cyclooxygenase-2 inhibitors 55
Monoaminergic antipsychotics 55
Muscarinic M(1) receptor agonists 55
Neurokinin 3 (NK3) receptor antagonists 56
Nicotinic acetylcholine receptor modulators 56
Secretin 56
Clinical trials and drug development 57
Clinical trial endpoints and schizophrenia rating scales 57
Positive and Negative Syndrome Scale 57
Brief Psychiatric Rating Scale 57
Brief Assessment of Cognition in Schizophrenia 57
Neuropsychological Assessment Battery 58
Other tests 58
A number of other tests are used in the diagnosis and monitoring of patients during general treatment management and for the duration of clinical trials: 58
Clinical trial design guidance 59
MATRICS recommendations for the clinical trial design for cognition enhancing drugs in schizophrenia 59
Key research recommendations 62
Increased focus on cost containment 63
Improved quality of life 64
CHAPTER 4 PIPELINE DRUG ANALYSIS 66
Pipeline overview 66
Approved drugs yet to be launched 66
Drugs in pre-registration 67
Pipeline drugs in Phase III 68
Pipeline drugs in Phase II 69
Pipeline drugs in Phase I 70
Key companies involved in the development of novel schizophrenia therapeutics 71
J&J’s schizophrenia franchise will decline from 2008 onwards despite the launch of paliperidone 71
Lundbeck’s experience with marketing sertindole will provide a strong base from which to launch bifeprunox 74
Organon’s asenapine will be an exciting entrant to the schizophrenia market 78
Pfizer’s schizophrenia franchise will continue to grow through 2011 81
Dainippon-Sumitomo’s blonanserin will first launch in Japan, despite competing with the recently launched Abilify 84
GSK’s antipsychotic pipeline drugs are unlikely to have a significant impact on the schizophrenia market 85
Methodology of Datamonitor’s competitive positioning analysis 88
Gold standard antipsychotic 90
The market value is calculated using IMS diagnosis value 92
Forecast caveats 94
CHAPTER 5 LATE-STAGE PIPELINE DRUG ANALYSIS AND FORECASTS 95
Paliperidone 95
Clinical trial data 95
Study 1 95
Study 2 96
Study 3 97
Study 4 98
Study 5 98
Study 6 99
Completed trials 100
Ongoing clinical trials 101
Physicians not overly impressed with paliperidone therapeutic profile 103
Paliperidone IM - an improvement over Risperdal Consta? 105
Risperdal patent expiry and switch to paliperidone over generic risperidone 107
How will J&J price paliperidone IM compared to Risperdal Consta 109
Paliperidone ER will be the next entrant to the US market in H2 2006 111
Intramuscular Zyprexa 114
Clinical trial data 114
Ongoing clinical trials 114
Zyprexa’s undesirable side-effect profile will limit the uptake of the long-acting IM formulation 114
Intramuscular Abilify 118
Clinical trial data 118
Study 1 118
Study 2 119
Study 3 120
Study 4 121
Study 5 121
Completed clinical trials 122
Abilify IM may lead to increased use of Abilify as a first-line maintenance therapy 123
Abilify needs to demonstrate strong efficacy in a head-to-head study 124
Multiple IM doses within a 24-hour period may limit use of Abilify IM compared to other IM formulations 125
How will Abilify IM be priced? 126
BMS/Otsuka should consider a long-acting IM version of Abilify 128
Sertindole 130
Clinical trial data 130
Study 1 130
Study 2 131
Study 3 132
Study 4 133
Study 5 133
Other clinical studies 134
Physicians not impressed with sertindole’s tolerability despite new data 135
Sertindole will be the next entrant to the EU market in H2 2006 139
Asenapine (Org-5222) 142
Clinical trial data 142
Study 1 142
Study 2 143
Study 3 144
Study 4 146
Ongoing clinical trials 146
Asenapine’s potential in treating negative symptoms will be a key therapeutic and commercial advantage 147
Twice daily dosing of asenapine may limit uptake 149
Asenapine will be the leading market entrant in terms of revenue value by 2015 152
Bifeprunox 155
Clinical trial data 155
Study 1 155
Additional clinical trial data 156
Completed clinical trials 156
Ongoing clinical trials 156
Bifeprunox’s tolerability is a key therapeutic and commercial attribute 157
Bifeprunox unlikely to be used for acute psychosis, but may have a niche in first episode psychosis 159
Bifeprunox’s pharmacokinetic profile is suitable for once-daily dosing, with a potential for numerous reformulation strategies 161
Solvay and Wyeth’s experience in psychiatry and Lundbeck’s launch of sertindole will provide a strong base for the commercialization of bifeprunox 162
Bifeprunox will be the second-highest new entrant in terms of cash value to the schizophrenia market by 2015 163
Blonanserin 166
Clinical trial data 166
Study 1 166
Study 2 166
Blonanserin demonstrates no clear advantages over marketed or pipeline schizophrenia drugs 167
Almirall’s limited commercial presence in the EU, and lack of presence in the US will limit uptake of blonanserin outside of Japan 169
Blonanserin will receive its strongest uptake in the Japanese market 170
Seroquel SR 173
Clinical trial data 173
Ongoing clinical trials 173
Seroquel SR unlikely to provide significant differentiation from Seroquel 174
Seroquel will retain patent protection until 2011, safeguarding the initial uptake of Seroquel SR from generic quetiapine 176
Will US health insurers pay the increased costs for the SR formulation? 177
Seroquel SR is not expected to receive a strong uptake, and revenues will decline from 2012 onwards 178
Iloperidone 180
Clinical trial data 180
Ongoing clinical trials 181
If approved, QT will limit iloperidone uptake as a first-line therapy 182
Iloperidone offers no therapeutic advantage over marketed or pipeline schizophrenia drugs 183
Iloperidone will receive limited uptake in the US 185
CHAPTER 6 PHASE II PIPELINE DRUG ANALYSIS 187
Introduction 187
ABT-089 187
Clinical trial data 187
Nicotinic agonists which improve cognitive functioning and smoking cessation would be valuable in the management of schizophrenia 188
ACP-103/ACP-104 189
ACP-103 clinical trial data 190
Study 1 190
Study 2 191
Study 3 192
Other trial data 192
Ongoing clinical trials 193
There is little need for an adjunct to improve positive symptoms, as marketed drugs already treat this domain of schizophrenia 193
ACP-104 clinical trial data 195
Study 1 195
Other trial data 196
Ongoing clinical trials 197
ACP-104 would be a significant treatment advance if it can demonstrate cognitive enhancement without the side effects of clozapine 198
AVE-1625 200
Dihydrexidine 202
Idazoxan 203
Clinical trial data 203
Study 1 203
Idazoxan is unlikely to be a standalone therapy, but may have a niche in treatment-resistant schizophrenia 204
Lurasidone 205
Clinical trial data 206
Completed clinical trials 206
Ongoing clinical trials 206
Lurasidone - another me-too atypical, and therefore of limited therapeutic and commercial potential 206
LY2140023 207
Ocaperidone 207
Clinical trial data 207
Study 1 207
Other clinical trial data 209
J&J may choose to relicense ocaperidone from Neuro3d if ocaperidone performs well in Phase II trials 209
Org-24448 210
Org-24448 may have potential in treating cognitive functioning 210
RG1068 213
Clinical trial data 213
Study 1 213
Other clinical trial data 214
Ongoing clinical trials 214
The subcutaneous formulation is unlikely be well received by patients 214
Sabcomeline 216
773812 (SB-750093A) 218
Clinical trial data 218
Completed clinical trials 218
Ongoing clinical trials 218
SCA-136 219
Clinical trial data 219
Ongoing clinical trials 219
SGS518 220
Clinical trial data 220
Study 1 220
Study 2 221
Commercial and patient potential 221
Talnetant 222
Clinical trial data 223
Study 1 223
Other study data 223
Completed clinical trials 224
Ongoing clinical trials 224
Pharmacokinetic profile may hamper talnetant’s clinical development 224
CHAPTER 7 FUTURE TREATMENT OF SCHIZOPHRENIA 226
Future treatment of schizophrenia 226
APPENDIX A 227
Forecast revenues 227
Competitive positioning analysis of pipeline schizophrenia drugs 228
Bibliography 230
Websites 230
Journal articles and conference abstracts 235
APPENDIX B 244
Report methodology 244
Datamonitor forecast methodology 244
Sales calculations 245
About Datamonitor 246
About Datamonitor Healthcare 246
Datamonitor Healthcare’s therapy area capabilities 247
List of Tables
Table 1: Diagnostic criteria for schizophrenia and its subtypes 24
Table 2: Prevalence of patients with schizophrenia exhibiting comorbid psychiatric disorders across the US, EU and Japan (%), 2005 26
Table 3: Risk factors for non-compliance to follow-up appointments and/or antipsychotics in patients with schizophrenia 33
Table 4: Potential strategies for improving compliance in patients with schizophrenia 35
Table 5: Novel antipsychotic drug classes in development for the treatment of schizophrenia,2006 52
Table 6: Approved drugs yet to be launched in the US, EU and Japan for the treatment of psychosis and schizophrenia, 2006 66
Table 7: Pipeline drugs in pre-registration for the treatment of psychosis and schizophrenia, 2006 67
Table 8: Pipeline drugs in Phase III development for psychosis and schizophrenia, 2006 68
Table 9: Pipeline drugs in Phase II development for psychosis and schizophrenia, 2006 69
Table 10: Pipeline drugs in Phase I development for psychosis and schizophrenia, 2006 70
Table 11: J&J’s pipeline schizophrenia drugs, 2006 72
Table 12: Lundbeck’s pipeline schizophrenia drugs, 2006 75
Table 13: Organon’s pipeline schizophrenia drugs, 2006 78
Table 14: Pfizer’s pipeline schizophrenia drugs, 2006 81
Table 15: Dainippon-Sumitomo’s pipeline schizophrenia drugs, 2006 84
Table 16: GSK’s pipeline schizophrenia drugs, 2006 86
Table 17: Commercial strength/weakness factors - weightings and scoring definitions 88
Table 18: Product-specific strength/weakness factors - weightings and scoring definitions 89
Table 19: Proportion of total molecule volume (SU and sales) of antipsychotics, accounted for by schizophrenia diagnoses in the US, EU and Japan, 2005 93
Table 20: Comparison of paliperidone IM versus Risperdal Consta 106
Table 21: Price of different formulations of Risperdal ($), 2001-05 109
Table 22: Revenues of the rapid-acting atypical antipsychotic IMs ($m), 2002-05 126
Table 23: Price points for the rapid-acting atypical antipsychotic IMs ($), 2004-06 127
Table 24: Asenapine can address most of the unmet needs for the treatment of schizophrenia 145
Table 25: Datamonitor’s forecast schizophrenia revenues of marketed and pipeline schizophrenia drugs across the US, EU and Japan ($m), 2006-2015 227
Table 26: Datamonitor’s competitive positioning analysis of pipeline schizophrenia drugs according to product-specific strength/weakness factors, 2006 228
Table 27: Datamonitor’s competitive positioning analysis of pipeline schizophrenia drugs according to commercial strength/weakness factors, 2006 229
Table 28: Schizophrenia market definition by ICD10 code 244
List of Figures
Figure 1: Forecast schizophrenia revenues of marketed and pipeline schizophrenia drugs across the US, EU and Japan, 2006-2015 7
Figure 2: Datamonitor’s competitive positioning analysis of pipeline schizophrenia drugs compared to marketed comparators, 2006 8
Figure 3: Reasons for non-compliance among schizophrenia patients receiving antipsychotic therapy 34
Figure 4: Drug classes in development for the treatment of schizophrenia, 2006 47
Figure 5: NICE measurement of cost-effectiveness of drug treatment 63
Figure 6: Forecast revenues for J&J’s schizophrenia franchise (Risperdal and paliperidone), 2006-2015 73
Figure 7: Datamonitor’s competitive positioning analysis of J&J’s marketed and pipeline schizophrenia drugs, 2006 73
Figure 8: Datamonitor’s competitive positioning analysis of Lundbeck’s pipeline schizophrenia drugs, 2006 75
Figure 9: Forecast revenues of Lundbeck’s schizophrenia franchise(Serdolect and bifeprunox (Lundbeck’s share - EU only), 2006-2015 77
Figure 10: Datamonitor’s competitive positioning analysis of Pfizer’s marketed and pipeline schizophrenia drugs, 2006 80
Figure 11: Forecast revenues of Organon’s schizophrenia franchise (asenapine), 2006-2015 80
Figure 12: Datamonitor’s competitive positioning analysis of Pfizer’s marketed and pipeline schizophrenia drugs, 2006 82
Figure 13: Forecast revenues of Pfizer’s schizophrenia franchise (Geodon and asenapine), 2006-2015 83
Figure 14: Paliperidone ER only meets one of the criteria for a therapeutically and commercially successful drug reformulation 104
Figure 15: Datamonitor’s competitive positioning analysis of paliperidone ER and IM, 2006 111
Figure 16: Datamonitor’s forecast of paliperidone’s revenues across the US, EU and Japan ($m), 2006-2015 113
Figure 17: Zyprexa’s declining US revenues, and plateauing EU revenues 115
Figure 18: Datamonitor’s competitive positioning analysis of Zyprexa IM, 2006 117
Figure 19: Datamonitor’s competitive positioning analysis of Abilify IM, 2006 128
Figure 20: Datamonitor’s competitive positioning analysis of sertindole, 2006 139
Figure 21: Datamonitor’s forecast of sertindole’s revenues across the five major EU markets ($m), 2006-2015 141
Figure 22: Datamonitor’s competitive positioning analysis of asenapine, 2006 152
Figure 23: Datamonitor’s forecast of asenapine’s revenues across the US, EU and Japan ($m), 2006-2015 154
Figure 24: Datamonitor’s competitive positioning analysis of bifeprunox, 2006 163
Figure 25: Datamonitor’s forecast of bifeprunox’s revenues across the US, EU and Japan ($m), 2006-2015 165
Figure 26: Datamonitor’s competitive positioning analysis of blonanserin, 2006 170
Figure 27: Datamonitor’s forecast of blonanserin’s revenues across the US, EU and Japan, 2006-2015 172
Figure 28: Seroquel SR meets two out of three criteria for a therapeutically and commercially successful drug reformulation 176
Figure 29: Datamonitor’s competitive positioning analysis of Seroquel SR, 2006 177
Figure 30: Datamonitor’s forecast of Seroquel SR’s revenues across the US, EU and Japan, 2006-2015 179
Figure 31: Datamonitor’s competitive positioning analysis of iloperidone, 2006 184
Figure 32: Datamonitor’s forecast of iloperidone’s revenues across the US, EU and Japan, 2006-2015 186
Figure 33: Polypharmacology affinity of atypical antipsychotics for serotonergic, dopaminergic, adrenergic, muscarinic and histaminergic receptors 223