Stakeholder Opinions: Systemic Lupus Erythematosus - On the Verge of a Breakthough

Table of Contents

• About the CNS, Arthritis and Pain pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Datamonitor insight into the lupus market
• CHAPTER 2 INTRODUCTION AND EPIDEMIOLOGY
  • Classifications
    • Diagnosis and severity - the "Chameleon" disease
      • Cutaneous or discoid lupus
      • Neuropsychiatric and CNS involvement in SLE
      • Neonatal lupus erythematosus
      • Drug-induced lupus erythematosus
    • Raynaud's phenomenon
  • Epidemiology of SLE
    • Datamonitor estimates a conservative SLE patient number
      • US SLE population is estimated between 200,000 and 1.5 million
      • European SLE demographics benefit from Euro-Lupus study but population estimate is indistinct
      • Japanese SLE population is especially difficult to estimate as data is rare
    • Improved SLE survival rates are increasing prevalence
      • Late morbidity risk increases as patients live longer
    • Genetic influences are key in SLE epidemiology
      • Race and ethnic segmentation - nature vs. nurture
    • Other suggested risk factors include environmental factors
• CHAPTER 3 CURRENT TREATMENT
  • Treatment algorithms vary with disease type
    • Non-pharmacological treatment largely involves education and avoidence of flare triggers
    • Pharmacological treatment currently revolves around steroids antimalarials and cytotoxic agents
      • Prednisone and Hydroxychloroquine are the mainstay of SLE treatment
    • Lupus nephritis is a key patient segment
    • Non-renal lupus includes joint, skin and CNS manifestations
      • Joint involvement
      • Dermatological involvement
      • CNS involvement and Neuropsychiatric (NP) symptoms
• CHAPTER 4 ASSESSMENT AND CLINICAL TRIAL DESIGN
  • Assessment criteria vary in popularity and usefulness in certain aspects of the disease
    • Systemic Lupus Erythematosus Activity Index (SLAM)
    • SLICC/ACR Damage Index
    • SLE Disease Activity Index (SLEDAI and SLENA-SLEDAI)
    • The British Isles Lupus Assessment Group (BILAG)
    • European Consensus Lupus Activity Measure (ECLAM)
  • Biomarker research aims to find an accurate, easily performed test for outcome or diagnostic purposes
  • Clinical trial design in SLE is a notoriously difficult task
    • Key challenges in the study of drug effects in Lupus
    • Specific trial designs
      • Dose ranging and Phase IIa and b trials
      • Disease activity
      • Superior safety/similar efficacy
      • Steroid sparing endpoints
    • Organ specific endpoints
      • Segmenting by lupus nephritis is a popular design, and invites off-label use in other SLE manifestations
      • Skin specific segmentation allows approval for a larger percentage of the overall lupus population as most will suffer from skin involvement
• CHAPTER 5 INCREASING SLE MARKET OPPORTUNITIES
  • Awareness is increasing but primary care physicians should be targeted
    • Misdiagnosis is a problem which is being addressed by the SLICC group
    • Increasing awareness and diagnosis by improved definition of SLE
  • Market potential can be based on estimated sales or cost to the healthcare system
    • Diagnosis value
    • Cost of SLE to the healthcare system
  • New treatments should be steroid sparing with a comparable side-effect profile to CellCept
    • Which cells play a major role in the SLE autoimmune response?
    • The risk-to-benefit profile in lupus depends on disease severity and the system affected
  • Orphan drug designation is a key opportunity
    • FDA requirements
    • EMEA requirements and possible advantages
  • Making use of patient advocacy groups and media advertising addresses challenges in clinical trial recruitment
    • The UK advantage
    • Recruitment
      • eRecruitment and making use of the media
      • Partnering with physican and patient organizations
• CHAPTER 6 PIPELINE DRUGS AND KEY TRIALS
  • Immunosuppressants
    • CellCept (mycophenolate mofetil)
    • Arava (leflunomide)
    • Riquent (abetimus)
  • B-cell therapy
    • Rituxan/MabThera (rituximab)
      • Cost
    • LymphoStat-B (belimumab)
    • Epratuzumab
  • Other cytokines suppression
    • Actemra (tocilizumab)
      • Liver enzyme irregularity with MRA is the current concern in both SLE and RA indications
    • CTLA4-Ig
      • Orencia (abatacept) - BMS
      • RG2077 - Repligen
  • Other pipeline possibilities
    • Gene therapy
    • Interferon suppression
    • DHEA (PrestaraT)
    • Autologous stem cell transplantation
    • Discoid and cutaneous lupus erythematosus
      • Topical immunomodulators - Protopic (tacrolimus) and Elidel (pimecrolimus)
      • Raptiva (efalizumab)
• APPENDIX
  • Contributing experts
  • Bibliography
    • Other sources
      • Government sites:
      • News sources:
      • American College of Rheumatology links:
      • Company websites:
      • Patient organizations:
      • Other
  • About Datamonitor
    • About Datamonitor Healthcare
    • Datamonitor Healthcare's research and analysis methodologies
    • Datamonitor Healthcare's therapy area capabilities
  • Disclaimer
  • List of Tables
    • Table 1: Range and frequency of symptoms associated with Lupus
    • Table 2: SLE population across the seven major markets, 2006
    • Table 3: Key SLE epidemiology studies
    • Table 4: Summary of key disease activity assessment tools
    • Table 5: WHO lupus nephritis classification, 1982
    • Table 6: Estimated sales for main drugs used in SLE, $ (000s), 2005
    • Table 7: Variations in prevalence criteria for orphan drug status
    • Table 8: Products in clinical development for lupus indications, 2006
    • Table 9: Actemra (tocilizumab) development schedule in all indications, March 2006
  • List of Figures
    • Figure 1: SLE system and general severity range
    • Figure 2: General treatments used for SLE
    • Figure 3: The risk and cost verses benefit profile for different severities of lupus symptoms
    • Figure 4: Geographical comparisons between the major research areas for lupus
    • Figure 5: Key messages to include when advertising for patient participation