Non-insulin Antidiabetics - Type 2 diabetes unlikely to develop into a switch market
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- About the cardiovascular pharmaceutical analysis team - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Scope of the analysis - page 3
- Datamonitor insight into the market for non-insulin antidiabetic pharmacotherapies - page 4
- The R&D pipeline for non-insulin antidiabetics is a mechanistically diverse collection of 77 novel agents at the clinical stages of drug development and dominated by a set of five pharmaceutical companies - page 4
- The diabetes market is characterized primarily by significant unmet clinical needs but also by some unmet market needs - page 5
- Datamonitor has identified two unmet market needs in the setting of diabetes. - page 6
- Datamonitor has identified two unmet clinical needs in the setting of diabetes. - page 7
- Datamonitor has identified five late-stage candidate drugs likely to be launched into the diabetes market within the next five years-the DPP-4 inhibitors Galvus (vildagliptin) and Januvia (sitagliptin), the GLP-1 agonists Byetta LAR (exenatide LAR) and liraglutide, and the specific PPAR-γ modulator metaglidasen. - page 8
- GLP-1 agonists - page 8
- DPP-4 inhibitors - page 9
- Metaglidasen - page 11
- CHAPTER 2 PIPELINE OVERVIEW - page 27
- Pipeline overview - page 27
- Non-insulin antidiabetic pipeline is mechanistically diversified - page 33
- Non-insulin antidiabetic pipeline is rich in Phase I and Phase II candidates - page 36
- The R&D landscape is dominated by five companies: GSK, Roche, Sanofi-Aventis, Merck & Co. and Novo Nordisk - page 38
- Pipeline overview - page 27
- CHAPTER 3 PATIENT POTENTIAL - page 42
- Definition of diabetes - page 42
- Segmentation of diabetes - page 42
- Type 1 diabetes - page 42
- Type 1.5 diabetes - page 42
- Type 2 diabetes - page 43
- Epidemiology of diabetes - page 45
- Current prevalence of type 1 and type 2 diabetes - page 45
- Methodology - page 49
- Future prevalence of type 2 diabetes - page 50
- Current prevalence of type 1 and type 2 diabetes - page 45
- Unmet need in diabetes - page 52
- Unmet market needs - page 52
- Unmet market need 1: routine screening for the detection of Type 2 diabetes mellitus - page 53
- Unmet market need 2: greater patient awareness - page 55
- Unmet market need 3: greater guideline awareness in physicians - page 56
- Unmet clinical needs - page 62
- Unmet clinical need 1: greater efficacy of non-insulin antidiabetics - page 65
- Unmet clinical need 2: better tolerability of non-insulin antidiabetics - page 66
- Unmet market needs - page 52
- CHAPTER 4 R&D APPROACH - page 71
- Therapy overview in type 1 and type 2 diabetes - page 71
- Type 1 diabetes - page 71
- Type 2 diabetes - page 75
- Comparator therapies - page 75
- Thiazolidinediones - page 75
- Weight gain associated with TZD therapy - page 77
- Actos (pioglitazone) - page 79
- Avandia (rosiglitazone) - page 79
- Sulfonylureas - page 80
- Amaryl - page 81
- Glucotrol XL - page 82
- Biguanides - page 82
- Glucophage (metformin) - page 84
- Other classes - page 85
- Thiazolidinediones - page 75
- Classification of pipeline products - page 85
- Incretin mimetics - page 85
- Gastric inhibitory polypeptide (GIP) - page 87
- Glucagon-like peptide-1 (GLP-1) - page 90
- Dipeptidyl PeptidaseIV (DPP-4 Inhibition - page 97
- PPAR agonists - page 98
- PPAR-γ agonists - page 98
- Dual PPAR agonists and PPAR pan agonists - page 99
- Sodium glucose co-transporter 2 (SGLT2) inhibitors - page 101
- Other classes of agents in development - page 102
- Inhibitors of glycogenolysis - page 102
- Glucokinase activation - page 102
- Incretin mimetics - page 85
- Clinical trial issues in diabetes - page 103
- Efficacy - page 103
- Control of average blood glucose levels (HbA1c) - page 103
- Bioavailability of non-invasive insulin - page 103
- Control of postprandial glucose levels - page 104
- Safety and side effects - page 104
- Incidence of hypoglycemic events - page 104
- Delivery-related complications - page 104
- Weight gain - page 105
- Patient compliance - page 105
- Efficacy - page 103
- Therapy overview in type 1 and type 2 diabetes - page 71
- CHAPTER 5 LATE-STAGE DRUG ANALYSIS & FORECASTS: NON-INSULIN ANTIDIABETICS - page 106
- Overview of pharmacotherapies in late-stage development for type 2 diabetes - page 106
- Pipeline summary - page 107
- DPP-4 inhibitor class - page 109
- Januvia (sitagliptin, MK-0431) - page 110
- Drug overview - page 110
- Clinical data - page 110
- Galvus (vildagliptin, LAF-237) - page 118
- Drug overview - page 118
- Clinical data - page 118
- Competitive environment of the DPP-4 inhibitor class - page 124
- Comparison with currently marketed oral antidiabetics - page 124
- Comparison with other late-stage pipeline agents - page 125
- Inter-class comparison of key clinical trial data of sitagliptin (Januvia) with vildagliptin (Galvus) - page 126
- SWOT analysis: Januvia (sitagliptin) - page 129
- SWOT analysis: Galvus (vildagliptin) - page 130
- Forecast: Galvus and Januvia - page 131
- Datamonitor comment - page 132
- Januvia (sitagliptin, MK-0431) - page 110
- GLP-1 class - page 139
- Byetta LAR (exenatide LAR) - page 139
- Drug overview - page 139
- Parent product: Byetta (exenatide), Byetta BID - page 140
- Clinical data - page 142
- Liraglutide (NN-2211) - page 143
- Drug overview - page 143
- Clinical data - page 143
- Competitive environment of the GLP-1 class - page 147
- Points of consideration: Byetta LAR - page 147
- Points of consideration: Liraglutide - page 153
- SWOT-Analysis: Byetta LAR (exenatide LAR) - page 157
- SWOT-Analysis: Liraglutide - page 158
- Forecast: Byetta LAR and liraglutide - page 158
- Datamonitor comment - page 161
- Byetta LAR (exenatide LAR) - page 139
- Metaglidasen (MBX-102) - page 162
- Drug overview - page 162
- Clinical data - page 163
- Phase II - page 164
- Competitive environment - page 165
- SWOT-Analysis: metaglidasen - page 166
- Forecast: metaglidasen - page 167
- Datamonitor comment - page 168
- Datamonitor does not believe non-injectable insulins to be able to compete with non-insulin antidiabetics - page 168
- Datamonitor drug assessment summary - page 169
- Overview of pharmacotherapies in late-stage development for type 2 diabetes - page 106
- CHAPTER 6 OTHER NON-INSULIN ANTIDIABETICS - page 176
- 625019 - page 176
- Drug overview - page 176
- 677954 - page 176
- Drug overview - page 176
- 825964 - page 176
- Drug overview - page 176
- 189075 - page 177
- Drug overview - page 177
- Ro-0730699 - page 177
- Drug overview - page 177
- DRF-2593 (Balaglitazone) - page 177
- Drug overview - page 177
- PHX-1149 - page 178
- Drug overview - page 178
- AMG-221 - page 178
- Drug overview - page 178
- APD-668 - page 179
- Drug overview - page 179
- Arimoclomol (BRX-345) - page 179
- Drug overview - page 179
- Anti-CD3 - page 179
- Drug overview - page 179
- Phase I/II clinical trials - page 180
- AVE-0847 - page 181
- Drug overview - page 181
- AVE-2268 - page 181
- Drug overview - page 181
- AVE-5376 - page 181
- Drug overview - page 181
- AVE-8134 - page 181
- Drug overview - page 181
- AZD-6610 - page 182
- Drug overview - page 182
- AZD-8677 - page 182
- Drug overview - page 182
- AVE-0010 (ZP-10) - page 182
- Drug overview - page 182
- Clinical data - page 182
- Phase IIa - page 182
- Phase IIb - page 183
- BAY-73-7977 - page 183
- Drug overview - page 183
- BI-1356-BS - page 183
- Drug overview - page 183
- BIM-51077 (ITM-077) - page 184
- Drug overview - page 184
- BLX-1002 - page 184
- Drug overview - page 184
- Clinical data - page 185
- Phase I - page 185
- Phase IIa - page 185
- CJC-1134-PC - page 185
- Drug overview - page 185
- Phase I/II - page 186
- CKD-501 - page 186
- Drug overview - page 186
- CS-917 (MB-6322) - page 186
- Drug overview - page 186
- Denagliptin (Redona, 823093) - page 187
- Drug overview - page 187
- Clinical data - page 187
- Diamyd (GAD-65) - page 187
- Drug overview - page 187
- Clinical data - page 188
- Phase II: 47 patients with latent autoimmune diabetes in adults (LADA) - page 188
- Phase II: 70 patients with recent onset type 1 diabetes - page 188
- Phase II/III: 160 patients with Latent Autoimmune Diabetes in Adults (LADA) - page 189
- DiaPep277 (AVE-0277) - page 189
- Drug overview - page 189
- Clinical data - page 189
- Phase II: 35 patients with newly diagnosed type 1 diabetes - page 189
- DIO-901 - page 190
- Drug overview - page 190
- DIO-902 - page 190
- Drug overview - page 190
- Clinical data - page 191
- Phase II - page 191
- EMD-387008 - page 191
- Drug overview - page 191
- EN-122004 - page 192
- Drug overview - page 192
- GRC-8200 - page 192
- Drug overview - page 192
- Phase I - page 192
- 716155 (albugon) - page 193
- Drug overview - page 193
- K-111 - page 193
- Drug overview - page 193
- KRP-104 - page 193
- Drug overview - page 193
- ISIS-113715 - page 193
- Drug overview - page 193
- Clinical data - page 194
- Phase I - page 194
- Phase II - page 194
- MB-07803 - page 194
- Drug overview - page 194
- MBX-2044 - page 195
- Drug overview - page 195
- MK-0533 - page 195
- Drug overview - page 195
- MK-0893 - page 195
- Drug overview - page 195
- MK-0941 - page 195
- Drug overview - page 195
- MP-513 - page 196
- Drug overview - page 196
- Naveglitazar (LY-818, LY519818) - page 196
- Drug overview - page 196
- iPlex (mecasermin rinfabate) - page 196
- Drug overview - page 196
- Clinical data - page 197
- Phase II: type 1 diabetes - page 197
- Phase II: type 1 diabetes - page 197
- Phase II: type 2 diabetes - page 198
- Phase II: type 2 diabetes - page 198
- Netoglitazone (MCC-555) - page 198
- Drug overview - page 198
- NN-0606 - page 199
- Drug overview - page 199
- NN-9101 - page 199
- Drug overview - page 199
- ONO-5129 - page 199
- Drug overview - page 199
- PLX-204 - page 199
- Drug overview - page 199
- PSN-010 - page 200
- Drug overview - page 200
- PSN-357 - page 200
- Drug overview - page 200
- PSN-9301 (P93/01) - page 200
- Drug overview - page 200
- Clinical data - page 201
- Phase IIa - page 201
- Phase IIa - page 201
- R-1438 - page 201
- Drug overview - page 201
- R-1439 - page 202
- Drug overview - page 202
- R-1440 - page 202
- Drug overview - page 202
- AVR-118 (reticulose, Product R) - page 202
- Drug overview - page 202
- CS-011 (rivoglitazone) - page 203
- Drug overview - page 203
- Saxagliptin (BMS-477118) - page 203
- Drug overview - page 203
- TS-033 - page 204
- Drug overview - page 204
- SGLT2 Inhibitor (lab code undisclosed) - page 204
- Drug overview - page 204
- Solabegron (427353) - page 204
- Drug overview - page 204
- SSR-162369 - page 205
- Drug overview - page 205
- CS-872 - page 205
- Drug overview - page 205
- SYR-322 - page 205
- Drug overview - page 205
- T-1095 - page 206
- Drug overview - page 206
- TA-6666 - page 206
- Drug overview - page 206
- TAK-654 - page 206
- Drug overview - page 206
- TH-0318 - page 206
- Drug overview - page 206
- Clinical data - page 207
- Phase I - page 207
- TS-021 - page 207
- Drug overview - page 207
- TRX-4 (agCD3) - page 207
- Drug overview - page 207
- Clinical data - page 208
- Phase I - page 208
- E1-INT - page 208
- Drug overview - page 208
- 625019 - page 176
- APPENDIX A - page 210
- Datamonitor drug assessment summary - page 210
- Bibliography - page 214
- Report methodology - page 233
- APPENDIX B - page 234
- About Datamonitor - page 234
- About Datamonitor Healthcare - page 234
- Datamonitor Healthcare's therapy area capabilities - page 235
- About the cardiovascular analysis team - page 236
- Disclaimer - page 237
- About Datamonitor - page 234
- List of Tables
- Table 1: Pipeline of non-insulin antidiabetic agents, 2006 - page 28
- Table 2: The pipeline for non-insulin antidiabetic agents is mechanistically diversified: full listing, 2006 - page 33
- Table 3: The pipeline for non-insulin antidiabetic agents is mechanistically diversified, 2006 - page 35
- Table 4: Acute pipeline of non-insulin antidiabetic agents by company, 2006 - page 38
- Table 5: Collaborative nature of R&D projects among key players in the non-insulin antidiabetic therapy sector, 2006 - page 40
- Table 6: Prevalence of diabetes mellitus is forecast to increase by the International Diabetes Foundation (IDF), 2003-2025 - page 46
- Table 7: Prevalence rate of type 1 and type 2 diabetes in the seven major markets (%), 2006-2015 - page 48
- Table 8: Estimated absolute prevalence of diabetes in the seven major markets (millions), 2006-2015 - page 50
- Table 9: Safety of pioglitazone - page 69
- Table 10: Comparator Oral Antidiabetics of the TZD Class - page 77
- Table 11: Weight gain associated with Actos (kg) - page 78
- Table 12: Weight gain associated with Avandia (kg) - page 78
- Table 13: Comparator oral antidiabetics of the sulfonylurea class - page 81
- Table 14: Metformin is the only representative of the biguanide class - page 82
- Table 15: Characteristics of GIP and GLP-1 - page 87
- Table 16: Key pipeline non-insulin antidiabetic therapies, 2006 - page 107
- Table 17: Trial data overview: Galvus, June 2006 - page 126
- Table 18: Trial data overview: Januvia, June 2006 - page 127
- Table 19: Key adverse event data comparing Januvia and Galvus as metformin adjuncts, 2006 - page 128
- Table 20: Sales forecast for Januvia, 2007-15 - page 131
- Table 21: Sales forecast for Galvus, 2007-15 - page 132
- Table 22: Comparison of GLP-1 agonists with DPP-4 inhibitors, 2006 - page 147
- Table 23: Comparative analysis of Byetta BID, Byetta LAR and liraglutide, 2006 - page 150
- Table 24: GLP-1 agonist class: Comparison between Byetta LAR and liraglutide, 2006 - page 155
- Table 25: Sales forecast for Byetta LAR, 2010-2015 - page 159
- Table 26: Sales forecast for liraglutide, 2009-15 - page 160
- Table 27: Sales forecast for metaglidasen, 2011-2015 - page 167
- Table 28: Research, clinical and commercial attractiveness of key pipeline non-insulin antidiabetics: basis dataset - page 172
- Table 29: Datamonitor drug assessment parameters - page 211
- List of Figures
- Figure 1: Pipeline of non-insulin antidiabetic drugs, 2006 - page 27
- Figure 2: The pipeline of non-insulin antidiabetic agents is mechanistically diverse, 2006 - page 36
- Figure 3: Pipeline maturity: percentage of R&D products in each phase of development, 2006 - page 37
- Figure 4: Collaborative nature of R&D projects among key players in the non-insulin antidiabetic therapy sector, 2006 - page 41
- Figure 5: Comparison of glucose testing - page 44
- Figure 6: Current NIADs do not address all medical aspects of type 2 diabetes - page 63
- Figure 7: Regulation of blood glucose levels by insulin, glucagon and amylin - page 73
- Figure 8: Mechanism of action of TZDs - page 76
- Figure 9: Mechanism of action of sulfonylureas and prandial glucose regulators - page 80
- Figure 10: Mechanism of action of metformin - page 83
- Figure 11: History of GLP-1, 1930-2006 - page 85
- Figure 12: Mechanism of action of GLP-1 - page 91
- Figure 13: GLP-1 effects on β cells - page 93
- Figure 14: Functional pancreatic effects of GLP-1 - page 94
- Figure 15: Mechanism of action of GLP-1 agonists - page 97
- Figure 16: Mechanism of action of DPP-4 inhibitors - page 98
- Figure 17: Combined theoretical benefits of PPAR pan agonists - page 100
- Figure 18: SWOT: Januvia (sitagliptin), 2006 - page 129
- Figure 19: SWOT: Galvus (vildagliptin), 2006 - page 130
- Figure 20: Sales forecast for Januvia and Galvus, 2007-2016 - page 131
- Figure 21: SWOT: Byetta LAR, 2006 - page 157
- Figure 22: SWOT: Liraglutide, 2006 - page 158
- Figure 23: Sales forecast for Byetta LAR, 2010-2015 - page 159
- Figure 24: Sales forecast for liraglutide, 2009-2015 - page 160
- Figure 25: SWOT: metaglidasen (MBX-102), 2006 - page 166
- Figure 26: Sales forecast for metaglidasen, 2011-2015 - page 167
- Figure 27: Overview of sales forecasts for the five pipeline agents analyzed in the present report, 2006-2015 - page 171
- Figure 28: Research, clinical and commercial attractiveness of key pipeline non-insulin antidiabetics: bubble chart - page 173
- Figure 29: Research, clinical and commercial attractiveness of late-stage candidate drugs in diabetes setting: radar plot - page 173
- Figure 30: Example of Datamonitor drug assessment scorecard - page 212
- Figure 31: Example of Datamonitor drug assessment graph - page 213
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