Pipeline Insight: Disease Modification In Rheumatoid Arthritis
Scope
Report Highlights
Reasons to Purchase
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE - page 2
- About the CNS, Arthritis and Pain pharmaceutical analysis team - page 2
- CHAPTER 1 EXECUTIVE SUMMARY - page 3
- Scope of the analysis - page 3
- Datamonitor insight into the RA market - page 4
- Summary - page 5
- CHAPTER 2 PATIENT POTENTIAL - page 17
- Definition of the disease - page 17
- Segmentation of RA - page 21
- US and northern Europe show a higher prevalence of RA across the seven major markets - page 21
- Average RA clinical trial participant is over 50 and female - page 22
- Decrease in RA severity due to better treatment but epidemiology research continues - page 24
- Key epidemiology studies in RA in the US, EU and Japan - page 26
- 2005 studies are coming from France and Canada but key Japanese studies need updating - page 26
- US - page 26
- Europe - page 30
- Japan - page 32
- Statistical caveats - page 33
- Prevalence versus incidence - page 33
- Diagnosed versus undiagnosed prevalence - page 34
- Different methods of gathering prevalence data - page 34
- Data ranges - page 34
- 2005 studies are coming from France and Canada but key Japanese studies need updating - page 26
- Unmet need in RA is still headed by efficacy - page 35
- Clinical unmet needs - page 36
- Efficacy - page 36
- Side effects - page 36
- Administration and patient compliance - page 38
- Cytokine assays a key challenge for treatment development - page 38
- Environmental unmet needs - page 39
- Cost - page 39
- Clinical unmet needs - page 36
- CHAPTER 3 R&D APPROACH - page 42
- The current treatment approach puts biologic therapy after different combinations of traditional DMARD treatments - page 43
- Current market definition includes the most common biologic and traditional DMARDs - page 44
- The Japanese market - page 45
- The market value is calculated using IMS diagnosis value - page 45
- Classification of pipeline products - page 46
- Cytokines - page 46
- Interleukins - page 47
- TNF inhibitors - page 50
- Cell adhesion molecule inhibitors - page 51
- MAP kinase - page 52
- Immunomodulators - page 53
- Other chemokines - page 56
- Clinical trial design - page 57
- Clinical trial endpoints in RA - page 59
- American College of Rheumatology (ACR) measures are the most common endpoints - page 59
- Disease Activity Scale - page 59
- Tender Joint Count and Swollen Joint Count - page 60
- Quality of Life Questionnaires - page 61
- HAQ - page 61
- Medical Outcome Short Form 36 (SF-36) Health Survey - page 62
- Blood testing - page 62
- Erythrocyte sedimentation rate (ESR) - page 62
- C-reactive proteins (CRP) - page 62
- Disease progression - page 62
- CHAPTER 4 RA PIPELINE ANALYSIS - page 64
- Pipeline overview - page 64
- Pre-registration and Phase III - page 66
- Phase II - page 67
- Key companies involved in the RA pipeline - page 70
- Roche dominates the late-stage pipeline - page 70
- Sanofi-Aventis is a key player in traditional DMARDs but has not broken into the biologic arena - page 72
- Strategies for success - page 73
- Improved dosing and administration methods will drive sales - page 73
- Patient preference or marketing strategies? - page 74
- Flexibility in dosing will be key - page 78
- Is a humanized Mab better than a chimeric one? - page 79
- Therapeutic antibody types - page 79
- The antibody misconception - page 82
- Mabs vs. therapeutic proteins vs. small molecules - page 84
- Biologic combinations should continue to be tested, but not in the near future - page 85
- Improved dosing and administration methods will drive sales - page 73
- Pipeline overview - page 64
- CHAPTER 5 TRADITIONAL DMARDS IN LATE STAGE DEVELOPMENT - page 87
- Overview for traditional DMARDs - page 87
- Pipeline summary - page 89
- Methotrexate is key comparator but Arava shows most innovation and highest sales in the traditional DMARD class - page 90
- Comparison of key compounds in the traditional DMARD class - page 91
- Prograf (tacrolimus) - page 92
- Drug overview - page 92
- Clinical trial data - page 93
- Tacrolimus will compete with cyclosporine and methotrexate but only possibility of modified release give it any advantage - page 95
- RA is just one more indication for Astellas's already top-selling drug - page 95
- Prograf competes in terms of cost and its oral administration, but side effects and comparative efficacy to biologics are major drawbacks - page 96
- Forecasts to 2014 - page 98
- US - page 98
- EU - page 98
- Japan - page 98
- Drug overview - page 92
- T-614 (iguratimod) - page 99
- Drug overview - page 99
- Clinical trial data - page 99
- A broad action for T-614 raises side-effect concerns - page 100
- Launch in Japan is more likely than in the US or EU - page 101
- ACR50 scores lacking in the latest data making clinical efficacy difficult to compare - page 101
- Forecasts to 2014 - page 102
- US - page 102
- EU - page 102
- Japan - page 102
- Drug overview - page 99
- Other traditional DMARDs - page 103
- Teriflunomide - page 103
- Rosaglitazone - page 103
- Overview for traditional DMARDs - page 87
- CHAPTER 6 BIOLOGIC DMARDS IN LATE-STAGE DEVELOPMENT - page 105
- Overview for biologic therapies - page 105
- Pipeline summary - page 105
- Current biologic comparator therapy is Enbrel - page 107
- Comparison of key compounds in biologic DMARD class - page 108
- Actemra (tocilizumab/MRA) - page 109
- Drug overview - page 109
- Clinical trial data - page 109
- IL-6 inhibition has potential in many immune disorders - page 112
- Chugai's new "Strategic Marketing Units" add considerable competitive strength to Actemra - page 113
- Actemra's IV dosing may prove more popular in Japan, which will be this product's key market - page 114
- Forecasts to 2014 - page 115
- US - page 115
- EU - page 115
- Japan - page 116
- Drug overview - page 109
- Rituxan/MabThera (rituximab) - page 116
- Drug overview - page 116
- Clinical trial data - page 117
- Rituximab's considerable use in the cancer market dispels any fears over side effects - page 121
- The Rituxan/MabThera brand has a strong marketing infrastructure behind it - page 122
- A minimal dosing frequency offers a considerable advantage for rituximab - page 123
- Forecasts to 2014 - page 125
- US - page 125
- EU - page 126
- Japan - page 126
- Drug overview - page 116
- Orencia (abatacept, CTLA4-Ig) - page 127
- Drug overview - page 127
- Clinical trial data - page 127
- Orencia's novel mechanism shows great promise in TNF-failures - page 133
- BMS may lack experience in the RA market, but its proposed pharmacovigilance program is well received by the FDA - page 134
- Orencia competes well in most clinical aspects - page 134
- Forecasts to 2014 - page 135
- US - page 136
- EU - page 136
- Japan - page 136
- Drug overview - page 127
- Cimzia (CDP 870) - page 137
- Drug overview - page 137
- Clinical trial data - page 137
- Crohn's disease is the primary indication for Cimzia - page 138
- A lack of recent data in RA may be losing physician faith in Cimzia, but ACR 2005 meeting data may save it - page 139
- Cost advantage needs to follow through for Cimzia to succeed - page 140
- Forecasts to 2014 - page 141
- US - page 141
- EU - page 141
- Japan - page 142
- Drug overview - page 137
- AMG-714 (HuMax Il-15) - page 142
- Drug overview - page 142
- Clinical trial data - page 143
- AMG-714 shows promise in many indications, including increase in BMD for osteoporosis - page 144
- Amgen's experience will be an advantage, but AMG-714 may reach the market too late - page 144
- AMG-714 offers yet another TNF-failure alternative - page 145
- Forecasts to 2014 - page 146
- US - page 146
- EU - page 146
- Drug overview - page 142
- LymphoStat-B (belimumab) - page 147
- Drug overview - page 147
- Clinical trial data - page 147
- BLyS shows promise in Lupus, which is expected to be the next major indication for biologic therapies - page 148
- HGS should seek a partner to bring this product to the RA market - page 149
- Initial ACR20 values not promising, but mechanism is sound - page 149
- Forecasts to 2014 - page 150
- Drug overview - page 147
- Other drugs in DMARD class - page 150
- RGN-303 (IL-1 Trap) - page 150
- SCIO-469 - page 151
- MLN 1202 - page 152
- VX-702 - page 152
- CNTO-148 - page 152
- AZD-9056 - page 153
- AT-001 (dnaJp1) - page 153
- AMG-162 - page 154
- Eculizumab (Mab C5) - page 154
- INCB-3284 - page 155
- AD 452 - page 155
- Recently discontinued late-stage development compounds - page 156
- CDP-484 - page 156
- ABT-874 - page 157
- ISIS-104838 - page 157
- Doramapimod (BIRB-796) - page 157
- AGIX 4207 - page 157
- Overview for biologic therapies - page 105
- CHAPTER 7 INNOVATIVE EARLY-STAGE PROJECTS - page 159
- Key Phase I and preclinical compounds in RA - page 159
- Phase I - page 160
- Preclinical - page 163
- CD20 directed therapy - page 170
- The candidates so far? - page 170
- HuMax-CD20 - page 170
- TRU 015 - page 171
- PR070769 - page 171
- Will they succeed? - page 172
- The candidates so far? - page 170
- BLyS inhibitor BR3-FC - page 172
- Less concern exists about long-term safety of BLyS antagonists - page 173
- Preliminary data from a similar pipeline product, LymphoStat-B, appear sub-par - page 173
- Key Phase I and preclinical compounds in RA - page 159
- APPENDIX A - METHODOLOGY, BIBLIOGRAPHY AND CONTRIBUTING EXPERTS - page 175
- Methodology - page 175
- Datamonitor forecast methodology - page 175
- Assumptions - page 175
- Company and product assessments - page 177
- Company factors and score definitions - page 177
- Product factors and score definitions - page 178
- Datamonitor forecast methodology - page 175
- Report methodology - page 179
- Definitions - page 179
- Standard units - page 179
- Japanese market data - page 179
- Derivation of sales forecasts and pricing trends - page 179
- Regional launch dates for new products - page 180
- Generic erosion and pricing assumptions - page 180
- Contributing experts - page 181
- Bibliography - page 181
- Websites - page 185
- Methodology - page 175
- APPENDIX B - FORECAST DATA TABLES - page 186
- US - page 186
- Japan - page 187
- France - page 188
- Germany - page 189
- Italy - page 190
- Spain - page 191
- UK - page 192
- 5 EU - page 193
- Global - page 194
- APPENDIX C - ABOUT DATAMONITOR - page 195
- About Datamonitor - page 195
- About Datamonitor Healthcare - page 195
- Datamonitor Healthcare's therapy area capabilities - page 196
- About the CNS, Arthritis and Pain analysis team - page 197
- Disclaimer - page 199
- About Datamonitor - page 195
- List of Tables
- Table 1: Global RA forecast, US$m, 2004-2014 - page 5
- Table 2: RA population by country, 2005 - page 21
- Table 3: Point prevalence of RA, by age and sex, per 100 patients in Norfolk UK study, 2002 - page 22
- Table 4: RA prevalence, by gender and country - page 23
- Table 5: Key American RA epidemiology studies - page 27
- Table 6: Key European RA epidemiology studies - page 30
- Table 7: Japan age-adjusted point prevalence of RA in nine consecutive surveys of the Kamitonda population, %, 1965-96 - page 33
- Table 8: Annual costs for biologic and traditional DMARDs, UK, 2000 - page 39
- Table 9: NICE incremental cost effectiveness ratio per QALY - page 40
- Table 10: Key interleukin targeted products in R&D pipeline, 2005 - page 49
- Table 11: TNF products in the pipeline, 2005 - page 50
- Table 12: Approved biologic TNF inhibitors - page 51
- Table 13: p38 MAP kinase targets in the RA pipeline - page 52
- Table 14: Immunosuppressant in the RA pipeline - page 54
- Table 15: Breakdown of other chemokine-targeted inhibitors in the pipeline, 2005 - page 56
- Table 16: Key trial data presented in prescribing information and used for approval of Enbrel and Remicade - page 58
- Table 17: DMARD pipeline breakdown, 2005 - page 64
- Table 18: Pre-registration and Phase III DMARDs in the pipeline, 2005 - page 66
- Table 19: Phase II DMARD pipeline, 2005 - page 67
- Table 20: Products undergoing human clinical trials in RA in collaboration with Roche - page 72
- Table 21: Advantages and disadvantages of IV and sc administration methods - page 75
- Table 22: Key traditional DMARDs on the market - page 88
- Table 23: Overview of late Phase traditional DMARDs - page 90
- Table 24: Results of trial to find optimal dosing of tacrolimus in refractory RA, %, 2004 - page 93
- Table 25: Tacrolimus Phase II trial results - page 94
- Table 26: Prograf Phase III trial results - page 94
- Table 27: Global franchise and clinical trial phase summary for Prograf, 2005 - page 96
- Table 28: Tacrolimus RA forecast by country, $m, 2005-14 - page 98
- Table 29: Iguratimod RA forecast, $m, 2005-2014 - page 102
- Table 30: Overview of late phase biologic DMARDs - page 106
- Table 31: Enbrel: key facts - page 108
- Table 32: MRA RA forecast by country, $m, 2005-2014 - page 115
- Table 33: Primary and secondary endpoints in rituximab's Phase IIb DANCER trial, 2005 - page 118
- Table 34: Clinical response over two years following a single treatment course of rituximab - page 121
- Table 35: Rituximab RA forecast by country, $m, 2005-2014 - page 125
- Table 36: Change from baseline in structural damage and progression, AIM trial - page 129
- Table 37: Infections seen in each treatment arm, % - page 131
- Table 38: Etanercept plus anakinra serious infection rates, % - page 131
- Table 39: Comparative one and two year trial results, % of patients achieving ACR20, 50 and 70 - page 132
- Table 40: Abatacept RA forecast by country, $m, 2005-2014 - page 135
- Table 41: CDP 870 Phase IIb trial results, 2001 - page 137
- Table 42: CDP 870 RA forecast by country, 2005-2014 - page 141
- Table 43: AMG-714 Phase II results - page 144
- Table 44: AMG 714 RA forecast by country, $m, 2005-2014 - page 146
- Table 45: LymphoStat-B Phase II RA trial results, 2005 - page 148
- Table 46: IL-1 Trap Phase II trial results, 2003 - page 151
- Table 47: Recently discontinued projects, 2005 - page 156
- Table 48: Phase I and preclinical targets, 2005 - page 159
- Table 49: Phase I DMARD pipeline, 2005 - page 160
- Table 50: Preclinical pipeline DMARDs, 2005 - page 163
- Table 51: CD20 directed therapies in the pipeline - page 170
- Table 52: ICD10 codes used to define an RA diagnosis - page 175
- Table 53: Company factors - page 177
- Table 54: Product factors - page 178
- Table 55: US RA forecast, US$, m, 2004-2014 - page 186
- Table 56: Japan RA forecast, US$m, 2004-2014 - page 187
- Table 57: France RA forecast, US$m, 2004-2014 - page 188
- Table 58: German RA forecasts, US$m, 2004-2014 - page 189
- Table 59: Italy RA forecast, US$m, 2004-2014 - page 190
- Table 60: Spain RA forecast, US$m, 2004-2014 - page 191
- Table 61: UK RA forecast, US$m, 2004-2014 - page 192
- Table 62: Five major EU countries RA forecast, US$m, 2004-2014 - page 193
- Table 63: Global RA forecast, US$m, 2004-2014 - page 194
- List of Figures
- Figure 1: The future RA market - page 5
- Figure 2: Normal and rheumatoid joint comparison - page 18
- Figure 3: Main cause of disability of civilian non-institutionalized people age 18 and over, %, 1999 - page 19
- Figure 4: Likely sites of action of the major novel drugs on the RA market - page 20
- Figure 5: RA prevalence, by gender and country - page 23
- Figure 6: Unmet needs in RA cited by physicians in Datamonitor primary research, 2003 - page 35
- Figure 7: Treatment algorithm for RA - page 43
- Figure 8: Historical sales for IL-1 inhibitor Kineret, Q3 2001-Q4 2004 - page 48
- Figure 9: Overview of Interleukin targets in the pipeline - page 49
- Figure 10: Mechanism of action of tacrolimus (FK506) and cyclosporine (CsA) - page 55
- Figure 11: Swollen and tender joint count assessment - page 61
- Figure 12: DMARD pipeline breakdown by mechanism or structure, Phase I to Pre-registration, 2005 - page 65
- Figure 13: Roche portfolio breakdown - page 71
- Figure 14: Biologic vs. traditional DMARD sales for RA in the US, 2004 - page 73
- Figure 15: Breakdown of late-stage projects by administration method, 2005 - page 74
- Figure 16: Improved self-administration syringe - page 76
- Figure 17: Enbrel retail vs. hospital sales, for all indications, Q2 2003 to Q1 2005 - page 77
- Figure 18: Patient preference for administration methods - page 78
- Figure 19: Definitions of antibody sections - page 80
- Figure 20: Illustration of Mab types - page 82
- Figure 21: Volume and value comparison of traditional DMARDs for RA, 2001-04 - page 89
- Figure 22: Traditional DMARDs company and product profiles - page 92
- Figure 23: Prograf comparative clinical profile - page 97
- Figure 24: T-614 comparative clinical profile - page 101
- Figure 25: Biologic DMARDs company and product comparison - page 109
- Figure 26: MRA ACR responses at 12 and 16 weeks - page 111
- Figure 27: MRA comparative clinical profile - page 114
- Figure 28: Primary Phase IIb DANCER results for rituximab, 2005 - page 118
- Figure 29: Prospective MabThera, and B-cell depiction, for rituximab in RA - page 123
- Figure 30: Rituximab comparative clinical profile - page 124
- Figure 31: AIM and ATTAIN trial results - page 128
- Figure 32: Abatacept comparative clinical profile - page 135
- Figure 33: Cimzia comparative clinical profile - page 140
- Figure 34: Comparison of German biologic uptake in RA, $m, 2001-04 - page 142
- Figure 35: AMG-714 comparative clinical profile - page 145
- Figure 36: LymphoStat-B comparative clinical profile - page 149
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