全身性エリテマトーデス：生物療法の時代

Abstract

Overview

Introduction

SLE is a chronic, life-long and potentially fatal autoimmune disease characterized by multiple system distress and unpredictable flares. Therapy is largely off-label and a huge demand exists for new SLE therapies because of the potential for serious side effects from drugs currently used in the management of the disease.

Scope

• Assessment of patient size across the seven major and additional emerging markets, including split by sex and race where available.
• Commercial and clinical assessment of the therapies in the developmental pipeline.
• Opinion of the market potential from a range of physicians involved in SLE treatment and research.
• An update of the challenges facing the design of clinical trials

Report Highlights

The SLE market will enter an era of targeted therapies thanks to greater understanding of disease mechanisms. Rituxan/MabThera (rituximab) is the most advanced pipeline candidate and will be the first product approved in the last 40 years. It is already used off-label in severe, refractory patients, with maximum estimated sales $650m.

Caution must be maintained as products for SLE have been prone to failure, as evidenced by La Jolla' s Riquent, Genelabs' s Prestara and Apreva' s CellCept. Companies must learn from past mistakes by improving SLE clinical trial design and communicating fully with regulatory agencies.

The SLE patient population in the seven major markets is estimated to be 430,000 in 2008. However, the combined SLE patient population in Mexico, China and India could be a minimum of 0.9 billion in 2008, suggesting pharmaceutical companies should seek product approval in emerging markets.

Reasons to Purchase

• Understand the key opportunities and threats in the SLE market
• Assess the commercial potential of the products in the late-stage pipeline
• Gain insight into opinion leaders' thoughts on the challenges facing the SLE market

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the Immunology and Inflammation (I&I) pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Datamonitor insight into the systemic lupus erythematosus market
  • Contributing experts
  • Related reports
  • Upcoming reports
• CHAPTER 2 EPIDEMIOLOGY
  • Lupus affects less than 1% of the population in the seven major markets
  • US
    • Datamonitor estimates a conservative SLE patient population in the US
    • Prevalence of lupus in Canada is similar to the US
    • Race and ethnic segmentation influence SLE in the US
      • Race is an important mediator of disease activity in SLE
      • Estimated SLE prevalent population in the US can be split by race
  • Japan
  • EU
    • UK
      • Lupus population split by sex in the UK
      • Lupus population split by race in the UK
    • UK prevalence rates can be applied to Germany
    • Prevalence rates from Spain can be applied to France
    • Italy
      • Lupus population split by sex in Italy
    • Spain
      • Lupus population split by sex in Spain
  • The SLE prevalent population will experience minimal growth over the next decade in the seven major markets
  • Countries of emerging markets represent a large SLE patient population
• CHAPTER 3 SLE MARKET
  • Drug approvals
    • Prograf (tacrolimus) approved for lupus nephritis in Japan
  • Clinical trial design
    • FDA' s recommendations for SLE drug development remain as draft guidance
    • Key challenges in clinical trials for SLE
  • Global opportunities and threats
    • Opportunities
      • High demand for products and level of unmet need provide a significant opportunity in the SLE market
      • Steroid-sparing therapies with improved side-effect profiles are needed
      • Understanding pathogenesis of SLE will help drive drug development
      • Potential for early use of biologics exists in SLE
      • Significant patient population in the emerging markets
    • Threats
      • Comparatively smaller patient population in the seven major markets
      • Lack of clarity from regulatory agencies
      • Difficulty and/or delay in diagnosis
      • Cost to healthcare systems of expensive therapies
      • Potential threat from biosimilars
  • Estimation of the size of the off-label SLE market in 2007
    • Estimation of Rituxan/MabThera costs for the treatment of SLE
      • Cost of Rituxan/MabThera in the seven major markets
      • Size of the SLE population receiving off-label Rituxan/MabThera
    • Diagnosis Value to establish retail sales of key brands
• CHAPTER 4 PIPELINE DRUGS AND KEY TRIALS
  • Majority of pipeline drugs are being developed for SLE specifically
  • Promising drug candidates in Phase III development
  • Competitive landscape of the late-stage pipeline
    • Estimation of Phase III product launch dates
    • Commercial versus clinical attractiveness of late-stage products
  • Immunosuppressants
    • Prestara/Aslera (prasterone)
      • After two failed Phase III studies, Genelabs secures SPA
      • Strong competition from targeted therapies drives Genelabs to search for late-stage development partner
      • Prestara: Strengths and weaknesses
    • Riquent (abetimus sodium)
      • La Jolla pushes on with another Phase III trial
      • Riquent: Strengths and weaknesses
  • B-cell therapy
    • Atacicept (TAC-Ig)
      • Phase Ib data confirm atacicept' s mechanism of action in SLE patients
      • Merck Serono partnership strengthens atacicept' s commercial potential
      • Atacicept has entered Phase II/III clinical trials for SLE and lupus nephritis
      • Atacicept: Strengths and weaknesses
    • Rituxan/MabThera (rituximab)
      • Rituxan is already prescribed off-label for SLE
      • Rituxan looks set to achieve first to market status
      • Small studies demonstrate efficacy of Rituxan in SLE
      • FDA raised safety concerns over the use of Rituxan in SLE patients
      • Rituxan/MabThera: Strengths and weaknesses
    • Ocrelizumab
      • Second generation humanized anti-CD20 MAb being developed for SLE
      • Potential for cannibalization of Rituxan/MabThera sales by ocrelizumab
      • Genentech and Biogen Idec embroiled in arbitration over ocrelizumab, which could affect its progress towards commercialization
      • Phase III clinical trials for ocrelizumab in SLE have been initiated
      • Ocrelizumab: Strengths and weaknesses
    • LymphoStat-B (belimumab)
      • Efficacy of belimumab has been demonstrated in Phase II trials by multiple disease activity indices in seropositive SLE patients
      • Phase III trials for belimumab
      • LymphoStat-B: Strengths and weaknesses
    • Epratuzumab
      • Phase III trials have resumed for SLE after regulatory agencies put clinical trials on hold
      • Epratuzumab: Strengths and weaknesses
  • Other cytokines suppression
    • Orencia (abatacept, CTLA4-Ig)
      • Orencia: Strengths and weaknesses
    • Actemra (tocilizumab)
    • Anti-TNF therapy: is there a place in the treatment of SLE?
      • Remicade (infliximab)
      • Enbrel (etanercept)
  • Recently discontinued drugs
    • CellCept (mycophenolate mofetil)
      • CellCept used off-label for systemic lupus erythematosus and is the standard of care in many patients
      • Development of CellCept for lupus nephritis on hold as trial fails to show superiority over Cytoxan
  • Drugs in development for cutaneous lupus erythematosus
    • CNTO-136
    • ASF-1096
    • TRX-1
• CHAPTER 5 BIBLIOGRAPHY
  • References
  • Websites
  • Datamonitor reports
• APPENDIX
  • Contributing experts
  • About Datamonitor
    • About Datamonitor Healthcare
    • Datamonitor Healthcare' s research and analysis methodologies
    • Datamonitor Healthcare' s therapy area capabilities
  • Disclaimer
  • List of Tables
    • Table 1: SLE population, split by sex, across the seven major markets, 2008
    • Table 2: Key prevalence and incidence studies of systemic lupus erythematosus, 1976-2008
    • Table 3: Estimate of persons with definite systemic lupus erythematosus in the US, split by race and sex, 2005
    • Table 4: Prevalence estimates of systemic lupus erythematosus in California and Pennsylvania, 2000
    • Table 5: Estimation of the systemic lupus erythematosus population in the US using prevalence figures reported by Chakravarty et al.
    • Table 6: Estimate of the systemic lupus erythematosus prevalent population in Canada, 2008
    • Table 7: Systemic lupus erythematosus prevalent population, split by race, in the US, 2008
    • Table 8: Systemic lupus erythematosus prevalent population, split by race, in the UK, 2008
    • Table 9: The estimated systemic lupus erythematosus prevalent population, split by sex, in the seven major markets, 2008-2018
    • Table 10: The estimated systemic lupus erythematosus prevalent population in the emerging markets of China, India and Mexico, 2008
    • Table 11: Phase III trial results for Prograf (tacrolimus) in lupus nephritis
    • Table 12: Cost of Rituxan/MabThera in the major 5EU markets and the US for the treatment of systemic lupus erythematosus
    • Table 13: Estimation of the off-label sales of Rituxan/MabThera in the treatment of systemic lupus erythematosus, 2008
    • Table 14: Datamonitor' s definition of systemic lupus erythematosus
    • Table 15: Estimated sales of the main drugs used in the treatment of systemic lupus erythematosus in the seven major markets, ($000s), 2007
    • Table 16: Products in development for lupus indications, 2008
    • Table 17: Summary of Phase III clinical trials for Prestara (prasterone), 1994-2004
    • Table 18: Overview of small-scale studies involving Rituxan/MabThera (rituximab) for lupus indications
    • Table 19: Overview of the Phase III clinical trial of ocrelizumab for systemic lupus erythematosus, 2008
    • Table 20: LymphoStat-B (belimumab): Key abstracts from ACR/ARHP Scientific Meetings 2006-07
    • Table 21: LymphoStat-B: Key clinical trials for lupus indications, 2008
    • Table 22: Orencia (abatacept): Key clinical trials for lupus indications, 2008
  • List of Figures
    • Figure 1: Potential strategies for improved clinical trial design or systemic lupus erythematosus
    • Figure 2: Opportunities and threats in the systemic lupus erythematosus market, 2008
    • Figure 3: Summary of the method used to estimate the sales of Rituxan/MabThera for systemic lupus erythematosus in the 6MM, 2008
    • Figure 4: Number of pipeline drugs in development split by lupus indication, 2008
    • Figure 5: Number of pipeline drugs in development for lupus erythematosus indications split by clinical phase, 2008
    • Figure 6: Timeline for estimated Phase III product launches for systemic lupus erythematosus, 2008-2016
    • Figure 7: Commercial and clinical assessment of key late-stage pipeline therapies for systemic lupus erythematosus, 2008
    • Figure 8: Prestara: Strengths and weaknesses for SLE, 2008
    • Figure 9: Riquent: Strengths and weaknesses for SLE, 2008
    • Figure 10: Atacicept: Strengths and weaknesses for SLE, 2008
    • Figure 11: Historical time line of approval of Rituxan for rheumatoid arthritis and estimation of approval timing for SLE indication
    • Figure 12: Rituxan/MabThera: Strengths and weaknesses for SLE, 2008
    • Figure 13: Ocrelizumab: Strengths and weaknesses for SLE, 2008
    • Figure 14: LymphoStat-B: Strengths and weaknesses for SLE, 2008
    • Figure 15: Epratuzumab: Strengths and weaknesses for SLE, 2008
    • Figure 16: Orencia: Strengths and weaknesses for SLE, 2008