Table of Contents
ABOUT DATAMONITOR HEALTHCARE
- About the CNS, Arthritis and Pain pharmaceutical analysisteam
CHAPTER 1 EXECUTIVE SUMMARY
- Scope of the analysis
- Datamonitor insight into the RA market
CHAPTER 2 PATIENT POTENTIAL
- Definition of the disease
- Segmentation of RA
- US and northern Europe show a higher prevalence of RAacross the seven major markets
- Average RA clinical trial participant is over 50 andfemale
- Decrease in RA severity due to better treatment butepidemiology research continues
- Key epidemiology studies in RA in the US, EU and Japan
- 2005 studies are coming from France and Canada but keyJapanese studies need updating
- Statistical caveats
- Prevalence versus incidence
- Diagnosed versus undiagnosed prevalence
- Different methods of gathering prevalence data
- Data ranges
- Unmet need in RA is still headed by efficacy
- Clinical unmet needs
- Efficacy
- Side effects
- Administration and patient compliance
- Cytokine assays a key challenge for treatment development
- Environmental unmet needs
CHAPTER 3 R&D APPROACH
- The current treatment approach puts biologic therapy afterdifferent combinations of traditional DMARD treatments
- Current market definition includes the most commonbiologic and traditional DMARDs
- The Japanese market
- The market value is calculated using IMS diagnosis value
- Classification of pipeline products
- Cytokines
- Interleukins
- TNF inhibitors
- Cell adhesion molecule inhibitors
- MAP kinase
- Immunomodulators
- Other chemokines
- Clinical trial design
- Clinical trial endpoints in RA
- American College of Rheumatology (ACR) measures are themost common endpoints
- Disease Activity Scale
- Tender Joint Count and Swollen Joint Count
- Quality of Life Questionnaires
- HAQ
- Medical Outcome Short Form 36 (SF-36) Health Survey
- Blood testing
- Erythrocyte sedimentation rate (ESR)
- C-reactive proteins (CRP)
- Disease progression
CHAPTER 4 RA PIPELINE ANALYSIS
- Pipeline overview
- Pre-registration and Phase III
- Phase II
- Key companies involved in the RA pipeline
- Roche dominates the late-stage pipeline
- Sanofi-Aventis is a key player in traditional DMARDs buthas not broken into the biologic arena
- Strategies for success
- Improved dosing and administration methods will drivesales
- Patient preference or marketing strategies?
- Flexibility in dosing will be key
- Is a humanized Mab better than a chimeric one?
- Therapeutic antibody types
- The antibody misconception
- Mabs vs. therapeutic proteins vs. small molecules
- Biologic combinations should continue to be tested, butnot in the near future
CHAPTER 5 TRADITIONAL DMARDS IN LATE STAGE DEVELOPMENT
- Overview for traditional DMARDs
- Pipeline summary
- Methotrexate is key comparator but Arava shows mostinnovation and highest sales in the traditional DMARD class
- Comparison of key compounds in the traditional DMARD class
- Prograf (tacrolimus)
- Drug overview
- Clinical trial data
- Tacrolimus will compete with cyclosporine and methotrexatebut only possibility of modified release give it any advantage
- RA is just one more indication for Astellass alreadytop-selling drug
- Prograf competes in terms of cost and its oraladministration, but side effects and comparative efficacy to biologics aremajor drawbacks
- Forecasts to 2014
- T-614 (iguratimod)
- Drug overview
- Clinical trial data
- A broad action for T-614 raises side-effect concerns
- Launch in Japan is more likely than in the US or EU
- ACR50 scores lacking in the latest data making clinicalefficacy difficult to compare
- Forecasts to 2014
- Other traditional DMARDs
- Teriflunomide
- Rosaglitazone
CHAPTER 6 BIOLOGIC DMARDS IN LATE-STAGE DEVELOPMENT
- Overview for biologic therapies
- Pipeline summary
- Current biologic comparator therapy is Enbrel
- Comparison of key compounds in biologic DMARD class
- Actemra (tocilizumab/MRA)
- Drug overview
- Clinical trial data
- IL-6 inhibition has potential in many immune disorders
- Chugais new "Strategic Marketing Units" addconsiderable competitive strength to Actemra
- Actemras IV dosing may prove more popular in Japan, whichwill be this products key market
- Forecasts to 2014
- Rituxan/MabThera (rituximab)
- Drug overview
- Clinical trial data
- Rituximabs considerable use in the cancer market dispelsany fears over side effects
- The Rituxan/MabThera brand has a strong marketinginfrastructure behind it
- A minimal dosing frequency offers a considerable advantagefor rituximab
- Forecasts to 2014
- Orencia (abatacept, CTLA4-Ig)
- Drug overview
- Clinical trial data
- Orencias novel mechanism shows great promise inTNF-failures
- BMS may lack experience in the RA market, but its proposedpharmacovigilance program is well received by the FDA
- Orencia competes well in most clinical aspects
- Forecasts to 2014
- Cimzia (CDP 870)
- Drug overview
- Clinical trial data
- Crohns disease is the primary indication for Cimzia
- A lack of recent data in RA may be losing physician faithin Cimzia, but ACR 2005 meeting data may save it
- Cost advantage needs to follow through for Cimzia tosucceed
- Forecasts to 2014
- AMG-714 (HuMax Il-15)
- Drug overview
- Clinical trial data
- AMG-714 shows promise in many indications, includingincrease in BMD for osteoporosis
- Amgens experience will be an advantage, but AMG-714 mayreach the market too late
- AMG-714 offers yet another TNF-failure alternative
- Forecasts to 2014
- LymphoStat-B (belimumab)
- Drug overview
- Clinical trial data
- BLyS shows promise in Lupus, which is expected to be thenext major indication for biologic therapies
- HGS should seek a partner to bring this product to the RAmarket
- Initial ACR20 values not promising, but mechanism is sound
- Forecasts to 2014
- Other drugs in DMARD class
- RGN-303 (IL-1 Trap)
- SCIO-469
- MLN 1202
- VX-702
- CNTO-148
- AZD-9056
- AT-001 (dnaJp1)
- AMG-162
- Eculizumab (Mab C5)
- INCB-3284
- AD 452
- Recently discontinued late-stage development compounds
- CDP-484
- ABT-874
- ISIS-104838
- Doramapimod (BIRB-796)
- AGIX 4207
CHAPTER 7 INNOVATIVE EARLY-STAGE PROJECTS
- Key Phase I and preclinical compounds in RA
- CD20 directed therapy
- The candidates so far?
- HuMax-CD20
- TRU 015
- PR070769
- Will they succeed?
- BLyS inhibitor BR3-FC
- Less concern exists about long-term safety of BLySantagonists
- Preliminary data from a similar pipeline product,LymphoStat-B, appear sub-par
- APPENDIX A - METHODOLOGY, BIBLIOGRAPHY AND CONTRIBUTINGEXPERTS
- Methodology
- Datamonitor forecast methodology
- Company and product assessments
- Company factors and score definitions
- Product factors and score definitions
- Report methodology
- Definitions
- Standard units
- Japanese market data
- Derivation of sales forecasts and pricing trends
- Regional launch dates for new products
- Generic erosion and pricing assumptions
- Contributing experts
- Bibliography
- APPENDIX B - FORECAST DATA TABLES
- US
- Japan
- France
- Germany
- Italy
- Spain
- UK
- 5 EU
- Global
- APPENDIX C - ABOUT DATAMONITOR
- About Datamonitor
- About Datamonitor Healthcare
- Datamonitor Healthcares therapy area capabilities
- About the CNS, Arthritis and Pain analysis team
- Disclaimer
List of Tables
- Table 1: Global RA forecast, US$m, 2004-2014
- Table 2: RA population by country, 2005
- Table 3: Point prevalence of RA, by age and sex, per 100patients in Norfolk UK study, 2002
- Table 4: RA prevalence, by gender and country
- Table 5: Key American RA epidemiology studies
- Table 6: Key European RA epidemiology studies
- Table 7: Japan age-adjusted point prevalence of RA innine consecutive surveys of the Kamitonda population, %, 1965-96
- Table 8: Annual costs for biologic and traditionalDMARDs, UK, 2000
- Table 9: NICE incremental cost effectiveness ratio perQALY
- Table 10: Key interleukin targeted products in R&Dpipeline, 2005
- Table 11: TNF products in the pipeline, 2005
- Table 12: Approved biologic TNF inhibitors
- Table 13: p38 MAP kinase targets in the RA pipeline
- Table 14: Immunosuppressant in the RA pipeline
- Table 15: Breakdown of other chemokine-targetedinhibitors in the pipeline, 2005
- Table 16: Key trial data presented in prescribinginformation and used for approval of Enbrel and Remicade
- Table 17: DMARD pipeline breakdown, 2005
- Table 18: Pre-registration and Phase III DMARDs in thepipeline, 2005
- Table 19: Phase II DMARD pipeline, 2005
- Table 20: Products undergoing human clinical trials inRA in collaboration with Roche
- Table 21: Advantages and disadvantages of IV and scadministration methods
- Table 22: Key traditional DMARDs on the market
- Table 23: Overview of late Phase traditional DMARDs
- Table 24: Results of trial to find optimal dosing oftacrolimus in refractory RA, %, 2004
- Table 25: Tacrolimus Phase II trial results
- Table 26: Prograf Phase III trial results
- Table 27: Global franchise and clinical trial phasesummary for Prograf, 2005
- Table 28: Tacrolimus RA forecast by country, $m, 2005-14
- Table 29: Iguratimod RA forecast, $m, 2005-2014
- Table 30: Overview of late phase biologic DMARDs
- Table 31: Enbrel: key facts
- Table 32: MRA RA forecast by country, $m, 2005-2014
- Table 33: Primary and secondary endpoints in rituximabsPhase IIb DANCER trial, 2005
- Table 34: Clinical response over two years following asingle treatment course of rituximab
- Table 35: Rituximab RA forecast by country, $m,2005-2014
- Table 36: Change from baseline in structural damage andprogression, AIM trial
- Table 37: Infections seen in each treatment arm, %
- Table 38: Etanercept plus anakinra serious infectionrates, %
- Table 39: Comparative one and two year trial results, %of patients achieving ACR20, 50 and 70
- Table 40: Abatacept RA forecast by country, $m,2005-2014
- Table 41: CDP 870 Phase IIb trial results, 2001
- Table 42: CDP 870 RA forecast by country, 2005-2014
- Table 43: AMG-714 Phase II results
- Table 44: AMG 714 RA forecast by country, $m, 2005-2014
- Table 45: LymphoStat-B Phase II RA trial results, 2005
- Table 46: IL-1 Trap Phase II trial results, 2003
- Table 47: Recently discontinued projects, 2005
- Table 48: Phase I and preclinical targets, 2005
- Table 49: Phase I DMARD pipeline, 2005
- Table 50: Preclinical pipeline DMARDs, 2005
- Table 51: CD20 directed therapies in the pipeline
- Table 52: ICD10 codes used to define an RA diagnosis
- Table 53: Company factors
- Table 54: Product factors
- Table 55: US RA forecast, US$, m, 2004-2014
- Table 56: Japan RA forecast, US$m, 2004-2014
- Table 57: France RA forecast, US$m, 2004-2014
- Table 58: German RA forecasts, US$m, 2004-2014
- Table 59: Italy RA forecast, US$m, 2004-2014
- Table 60: Spain RA forecast, US$m, 2004-2014
- Table 61: UK RA forecast, US$m, 2004-2014
- Table 62: Five major EU countries RA forecast, US$m,2004-2014
- Table 63: Global RA forecast, US$m, 2004-2014
List of Figures
- Figure 1: The future RA market
- Figure 2: Normal and rheumatoid joint comparison
- Figure 3: Main cause of disability of civiliannon-institutionalized people age 18 and over, %, 1999
- Figure 4: Likely sites of action of the major noveldrugs on the RA market
- Figure 5: RA prevalence, by gender and country
- Figure 6: Unmet needs in RA cited by physicians inDatamonitor primary research, 2003
- Figure 7: Treatment algorithm for RA
- Figure 8: Historical sales for IL-1 inhibitor Kineret,Q3 2001-Q4 2004
- Figure 9: Overview of Interleukin targets in thepipeline
- Figure 10: Mechanism of action of tacrolimus (FK506) andcyclosporine (CsA)
- Figure 11: Swollen and tender joint count assessment
- Figure 12: DMARD pipeline breakdown by mechanism orstructure, Phase I to Pre-registration, 2005
- Figure 13: Roche portfolio breakdown
- Figure 14: Biologic vs. traditional DMARD sales for RAin the US, 2004
- Figure 15: Breakdown of late-stage projects byadministration method, 2005
- Figure 16: Improved self-administration syringe
- Figure 17: Enbrel retail vs. hospital sales, for allindications, Q2 2003 to Q1 2005
- Figure 18: Patient preference for administration methods
- Figure 19: Definitions of antibody sections
- Figure 20: Illustration of Mab types
- Figure 21: Volume and value comparison of traditionalDMARDs for RA, 2001-04
- Figure 22: Traditional DMARDs company and productprofiles
- Figure 23: Prograf comparative clinical profile
- Figure 24: T-614 comparative clinical profile
- Figure 25: Biologic DMARDs company and productcomparison
- Figure 26: MRA ACR responses at 12 and 16 weeks
- Figure 27: MRA comparative clinical profile
- Figure 28: Primary Phase IIb DANCER results forrituximab, 2005
- Figure 29: Prospective MabThera, and B-cell depiction,for rituximab in RA
- Figure 30: Rituximab comparative clinical profile
- Figure 31: AIM and ATTAIN trial results
- Figure 32: Abatacept comparative clinical profile
- Figure 33: Cimzia comparative clinical profile
- Figure 34: Comparison of German biologic uptake in RA,$m, 2001-04
- Figure 35: AMG-714 comparative clinical profile
- Figure 36: LymphoStat-B comparative clinical profile
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