Disease Modification in Rheumatoid Arthritis - Competition for the anti-TNF failure
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- About the Immune Disorders and Inflammation (IDI) pharmaceutical analysis team - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Scope of the analysis - page 3
- Datamonitor insight into the rheumatoid arthritis market - page 4
- Key metrics - page 5
- Datamonitor Pipeline Assessment Summary - page 6
- CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS - page 18
- Pipeline overview - page 18
- Key companies involved in the rheumatoid arthritis pipeline - page 26
- Roche and partners - page 26
- Mutually beneficial partnerships - page 27
- Roche and partners - page 26
- Key R&D company strategies - page 27
- Small molecules - is it feasible? - page 27
- CHAPTER 3 RHEUMATOID ARTHRITIS - MARKET POTENTIAL - page 30
- Definition of rheumatoid arthritis - page 30
- Epidemiology of rheumatoid arthritis - page 31
- Segmentation of rheumatoid arthritis - page 37
- Mild, moderate and severe patients - page 37
- Early active rheumatoid arthritis - page 38
- Anti-TNF failure population - page 39
- Patient potential for anti-TNF failure drugs - page 41
- Current market overview - page 43
- Unmet needs in rheumatoid arthritis - page 45
- Environmental unmet need - page 47
- Cost and reimbursement is a barrier to extensive use of some DMARDs - page 47
- Clinical trial design - page 48
- Clinical unmet need - page 50
- Disease modification and side effects are the most important factors to prescribing physicians - page 50
- Predicting response - page 53
- Environmental unmet need - page 47
- CHAPTER 4 R&D APPROACH - page 55
- Classification of pipeline products - page 55
- Cytokine T cell targets - page 55
- Interleukins - page 56
- TNF inhibitors - page 57
- Co-stimulatory pathways - page 59
- Cytokine B cell targets - page 59
- CD20 - page 62
- Other B-cell mechanisms - page 62
- Small molecules - page 63
- MAP kinase - page 64
- Chemokines - page 65
- Cytokine T cell targets - page 55
- Clinical trial design - page 66
- Non-responder clinical trials - page 67
- What is remission? - page 68
- Clinical trial endpoints in RA - page 70
- American College of Rheumatology (ACR) measures are the most common endpoints - page 70
- Disease Activity Scale - page 70
- Tender Joint Count and Swollen Joint Count - page 71
- Quality of Life questionnaires - page 72
- HAQ - page 72
- Medical Outcome Short Form 36 (SF-36) Health Survey - page 73
- Disease progression - page 73
- Total Sharp Score - page 74
- Classification of pipeline products - page 55
- CHAPTER 5 BIOLOGIC LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 76
- Overview for the biologic class - page 76
- Biologic pipeline summary - page 76
- Comparative forecasts - page 77
- Definition of current comparator therapy - page 79
- Orencia (abatacept) - page 81
- Drug overview - page 81
- Clinical trial data - page 82
- More two-year data for abatacept - page 85
- A rare head-to-head trial with infliximab - page 89
- Data in JIA - page 91
- Patient potential - page 94
- Marketing factors - page 96
- Satisfaction of unmet needs - page 97
- Forecasts to 2016 - page 100
- US - page 100
- EU - page 101
- Japan - page 102
- Datamonitor drug assessment summary - page 103
- Actemra (tocilizumab) - page 104
- Drug overview - page 104
- Clinical trial data - page 104
- Results on three key trials presented at the ACR Annual Meeting 2006 - page 104
- Press release Phase III data - page 106
- Radiographic progression targeted at ACR - page 107
- European trial has more realistic results - page 109
- Tocilizumab in JIA - page 110
- Patient potential - page 113
- Marketing factors - page 113
- Satisfaction of unmet needs - page 114
- Forecasts to 2016 - page 116
- US - page 117
- EU - page 117
- Japan - page 118
- Datamonitor drug assessment summary - page 119
- Ocrelizumab (rhuMab 2H7) - page 119
- Profile - page 119
- Clinical trial data - page 120
- The ACTION study results - page 121
- Patient potential - page 123
- Marketing potential - page 123
- Satisfaction of unmet needs - page 124
- Forecasts to 2016 - page 125
- US - page 126
- EU - page 126
- Japan - page 127
- Datamonitor drug assessment summary - page 127
- Cimzia (certolizumab) - page 128
- Drug overview - page 128
- Clinical trial data - page 128
- Positive signals but still no fully published data on Cimzia - page 128
- Phase IIb results - page 130
- Patient potential - page 130
- Marketing factors - page 131
- Satisfaction of unmet needs - page 133
- Forecasts to 2016 - page 134
- US - page 134
- EU - page 135
- Japan - page 135
- Datamonitor drug assessment summary - page 135
- Golimumab - page 136
- Drug overview - page 136
- Clinical trial data - page 137
- Patient potential - page 140
- Smart trial design segments the RA population - page 140
- Marketing factors - page 140
- Satisfaction of unmet needs - page 142
- Forecasts to 2016 - page 142
- US - page 143
- EU - page 143
- Japan - page 144
- Datamonitor drug assessment summary - page 145
- Atacicept (TACI-Ig) - page 146
- Drug overview - page 146
- Clinical trial data - page 147
- Patient potential - page 148
- SLE offers a higher unmet need than RA but a difficult route to approval - page 148
- Marketing factors - page 148
- Clinical development partnerships boost atacicept's commercial viability - page 148
- Satisfaction of unmet need - page 149
- Forecast to 2016 - page 149
- Ofatumumab (HuMax-CD20) - page 150
- Drug overview - page 150
- Clinical trials data - page 150
- Patient potential - page 153
- NHL as primary indication creates more direct competition with Rituxan/MabThera - page 153
- Market potential - page 153
- Genmab's alliances add commercial value - page 153
- Satisfaction of unmet needs - page 154
- Forecast to 2016 - page 155
- US - page 155
- EU - page 155
- Japan - page 156
- Datamonitor drug assessment summary - page 156
- AMG 714 (HuMax Il-15) - page 157
- Drug overview - page 157
- Clinical trial data - page 157
- Patient potential - page 160
- Marketing factors - page 160
- Satisfaction of unmet needs - page 161
- Forecasts to 2016 - page 162
- Other drugs in the biologic DMARD class - page 162
- TRU-015 - page 162
- Denosumab - page 163
- Late-stage development compounds recently discontinued - page 164
- Cell adhesion molecule inhibitors - page 164
- Overview for the biologic class - page 76
- CHAPTER 6 SMALL MOLECULE LATE-STAGE DRUG ANALYSIS AND FORECASTS - page 165
- Overview for the small molecules - page 166
- Small molecule pipeline summary - page 166
- Definition of current comparator - page 169
- Careram (iguratimod, T-614) - page 170
- Drug overview - page 170
- Clinical trial data - page 170
- Patient potential - page 172
- Increased liver enzymes create concern - page 172
- Lack of disease modifying effects - page 172
- Market factors - page 173
- Launch in Japan is more likely than in the US or EU - page 173
- ACR50 scores lacking in the latest data making clinical efficacy difficult to compare - page 173
- Satisfaction of unmet needs - page 173
- Forecasts to 2016 - page 174
- US and EU - page 174
- Japan - page 174
- CF101 - page 175
- Drug overview - page 175
- Clinical trial data - page 175
- Patient potential - page 177
- Marketing factors - page 177
- Satisfaction of unmet need - page 178
- Forecast to 2016 - page 179
- CP-690550 - page 179
- Overview - page 179
- Clinical trial data - page 180
- Patient potential - page 182
- Marketing factors - page 183
- Satisfaction of unmet need - page 184
- Forecast to 2016 - page 184
- US - page 185
- EU - page 186
- Japan - page 186
- Other small molecules - page 186
- VX-702 - page 186
- AT-001 (dnaJP1) - page 187
- R-788 - page 188
- ABN-912 - page 189
- RhuDex - page 190
- Apilimod mesylate (STA-5326) - page 190
- SCIO-469 - page 191
- MLN-3897 - page 191
- Late-stage development compounds recently discontinued - page 192
- Apratastat (TMI-005, APS) - page 192
- MK-0812 - page 192
- Overview for the small molecules - page 166
- CHAPTER 7 INNOVATIVE EARLY-STAGE PROJECTS - page 194
- Preclinical and discovery compounds - page 194
- BIBLIOGRAPHY - page 203
- Webpages - page 212
- APPENDIX A - page 214
- Methodology - page 214
- Datamonitor forecast methodology - page 214
- IMS Assumptions - page 214
- Product forecasts - page 215
- Definition of a standard unit - page 215
- Datamonitor drug assessment summary - page 215
- Datamonitor forecast methodology - page 214
- Contributing experts - page 216
- Report methodology - page 216
- Methodology - page 214
- APPENDIX B - page 217
- About Datamonitor - page 217
- About Datamonitor Healthcare - page 217
- Datamonitor Healthcare's therapy area capabilities - page 218
- About the Disease analysis team - page 219
- Disclaimer - page 220
- About Datamonitor - page 217
- List of Tables
- Table 1: Prevalence of RA in 2007 - page 5
- Table 2: Products in late-phase development for rheumatoid arthritis, 2007 - page 20
- Table 3: Roche's recently launched and pipeline RA products, 2007 - page 26
- Table 4: Prevalence of rheumatoid arthritis in the seven major markets, 2007 - page 32
- Table 5: RA prevalence applied to growing population rates in the seven major markets, 2006-2016 - page 33
- Table 6: Epidemiology studies into rheumatoid arthritis, 1955-2005 - page 34
- Table 7: Point prevalence of rheumatoid arthritis by age and sex per 100 patients in Norfolk, UK study, 2002 - page 36
- Table 8: CAGR for over-60 population in the seven major markets, 2005-2015 - page 37
- Table 9: Rheumatoid arthritis disease severity as a percentage of total diagnosed RA population in the seven major markets (%), 2006 - page 38
- Table 10: Physician-estimated proportion of patients defined as having early active rheumatoid arthritis in the seven major markets, 2006 - page 39
- Table 11: Estimation of anti-TNF failure patient population in the seven major markets, 2006-2016 - page 42
- Table 12: Interleukin targeting products in the rheumatoid arthritis pipeline, 2007 - page 57
- Table 13: TNF products in the pipeline for rheumatoid arthritis, 2007 - page 58
- Table 14: Approved biologic TNF inhibitors in rheumatoid arthritis across the seven major markets, 2007 - page 59
- Table 15: CD20 targets in human clinical trials for rheumatoid arthritis,, 2007 - page 62
- Table 16: Other B-cell targeting therapies in human clinical trials, 2007 - page 62
- Table 17: Oral p38 MAP kinase targets in clinical trials for rheumatoid arthritis, 2007 - page 64
- Table 18: CCR2 targets in human trials in rheumatoid arthritis, 2007 - page 65
- Table 19: CCR1 targets in human trials for rheumatoid arthritis in the US, 2007 - page 66
- Table 20: Key trial data presented in prescribing information and used for approval of Enbrel and Remicade - page 67
- Table 21: Key biologic products in the late-stage pipeline for rheumatoid arthritis, 2007 - page 77
- Table 22: Sales forecasts for biologic drugs in rheumatoid arthritis across the seven major markets, 2007-2016 - page 78
- Table 23: Enbrel clinical efficacy, study IV from prescribing information - page 80
- Table 24: Enbrel: key facts - page 80
- Table 25: Orencia: prescribing information - page 82
- Table 26: Published key Phase III abatacept studies, 2007 - page 83
- Table 27: Percentage of ACR responders during the open-label period of the ATTAIN trial in patients who were originally randomized to abatacept (ITT and as-observed analysis) - page 86
- Table 28: Mean percentage improvement from baseline through 2 years in the ASSURE Trial - page 88
- Table 29: Abatacept: safety summary - page 89
- Table 30: Results of abatacept versus infliximab - page 90
- Table 31: Cost comparison from Abatacept monograph from US Dept of Veterans Affairs, 2006 - page 98
- Table 32: Orencia: satisfaction of unmet needs - page 99
- Table 33: Percentage of patients in ITT analysis reaching ACR70 when receiving 8mg/kg of tocilizumab or placebo - page 105
- Table 34: Percentage of patients in ITT analysis reaching DAS28 remission when receiving 8mg/kg of tocilizumab or placebo - page 106
- Table 35: Actemra preliminary Phase III results - page 107
- Table 36: Actemra: satisfaction of unmet needs - page 116
- Table 37: Results of ocrelizumab's Phase I/II ACTION study, at week 24 - page 122
- Table 38: Ocrelizumab: satisfaction of unmet needs - page 124
- Table 39: Cimzia Phase IIb trial results at week 12, 2001 - page 130
- Table 40: Cimzia: satisfaction of unmet needs - page 133
- Table 41: ACR20/50/70 and DAS28 assessments at weeks 16 and 52 for all treatment arms - page 138
- Table 42: Golimumab: satisfaction of unmet needs - page 142
- Table 43: Atacicept: satisfaction of unmet need - page 149
- Table 44: Patient baseline demographics for Phase II trial for HuMax-CD20 in rheumatoid arthritis - page 151
- Table 45: Ofatumumab 24-week clinical response rates per dose group for Phase II trial for HuMax-CD20 in rheumatoid arthritis, % of patients - page 151
- Table 46: Ofatumumab: satisfaction of unmet needs - page 154
- Table 47: AMG 714 Phase II ACR20 results at weeks 12, 14 and 16 - page 159
- Table 48: AMG 714: satisfaction of unmet need - page 162
- Table 49: Forecast sales for small molecule disease modifying agents in development for rheumatoid arthritis across the seven major markets ($m), 2007-2016 - page 167
- Table 50: Small molecule agents in the pipeline for rheumatoid arthritis, 2007 - page 167
- Table 51: Careram: satisfaction of unmet need - page 173
- Table 52: CF101 satisfaction of unmet need - page 178
- Table 53: CP-690550: Phase II trial-week 6 responses - page 181
- Table 55: CP-690550: Phase II trial - numbers withdrawn - page 181
- Table 54: CP-690550: satisfaction of unmet need - page 184
- Table 55: Preclinical and discovery RA projects in the seven major markets, 2007 - page 195
- Table 56: ICD10 codes used to define an RA diagnosis - page 214
- Table 58: Datamonitor drug assessment tool - factors and weightings - page 215
- List of Figures
- Figure 1: Total RA sales and SUs in the seven major markets by region, 2003-06 - page 5
- Figure 2: Datamonitor drug assessment summary for RA - page 6
- Figure 3: Breakdown of rheumatoid arthritis clinical projects by phase, 2007 - page 18
- Figure 4: Rheumatoid arthritis pipeline broken down by mechanism, 2007 - page 19
- Figure 5: Pipeline broken down by administration method and molecule type, 2007 - page 28
- Figure 6: Likely sites of action of the major novel drugs on the RA market, 2007 - page 31
- Figure 7: Percentage of patients on biologics switching or terminating therapy, and key reasons, 2006 - page 40
- Figure 8: Total RA sales and SUs in the seven major markets by region, 2003-06 - page 43
- Figure 9: The top rheumatoid arthritis products/molecules in the seven major markets market, 2005-06 - page 44
- Figure 10: Importance of challenges facing the rheumatoid arthritis market, 2006 - page 46
- Figure 11: Average influence on prescribing decision: weightings assigned by surveyed physicians to key attributes for biologic and traditional DMARDs - page 51
- Figure 12: Normal and rheumatoid joint comparison - page 55
- Figure 13: Suggested mechanism for B cell activation in rheumatoid arthritis - page 60
- Figure 14: Breakdown of small molecules in human clinical trials for RA by mechanism, 2007 - page 63
- Figure 15: Swollen and tender joint count assessment - page 72
- Figure 16: Datamonitor drug assessment summary of biologic disease modifying drugs in late-stage development for rheumatoid arthritis, 2007-2016 - page 76
- Figure 17: Sales forecasts for biologic drugs in rheumatoid arthritis across the seven major markets, 2007-2016 - page 78
- Figure 18: Orencia's novel mechanism - page 81
- Figure 19: Bristol-Myers Squibb's strategy for Orencia, February 2007 - page 95
- Figure 20: Orencia's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016 - page 100
- Figure 21: Datamonitor drug assessment summary for Orencia in late-stage development for rheumatoid arthritis - page 103
- Figure 22: Actemra's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016 - page 117
- Figure 23: Datamonitor drug assessment summary for Actemra in late-stage development for rheumatoid arthritis - page 119
- Figure 24: Results of ocrelizumab's Phase I/II ACTION study, at week 24 - page 122
- Figure 25: Ocrelizumab's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016 - page 126
- Figure 26: Datamonitor drug assessment summary for Ocrelizumab in late-stage development for rheumatoid arthritis - page 127
- Figure 27: Cimzia's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016 - page 134
- Figure 28: Datamonitor drug assessment summary for Cimzia in late-stage development for rheumatoid arthritis - page 136
- Figure 29: Golimumab's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016 - page 143
- Figure 30: Datamonitor drug assessment summary for golimumab in late-stage development for rheumatoid arthritis - page 145
- Figure 31: Atacicept: mechanism of action - page 146
- Figure 32: Ofatumumab's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016 - page 155
- Figure 33: Datamonitor drug assessment summary for ofatumumab in late-stage development for rheumatoid arthritis - page 156
- Figure 34: Datamonitor drug assessment summary of small molecule disease modifying agents in late-stage development for rheumatoid arthritis - page 166
- Figure 35: Careram's forecast revenues in rheumatoid arthritis in Japan only ($m), 2007-2016 - page 174
- Figure 36: CF101 preliminary Phase IIa results at 12 weeks - page 176
- Figure 37: CP-690550's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016 - page 185
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