Stakeholder Opinions: Systemic Lupus Erythematosus - Market set to enter era of biologic therapies
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 trialsHighlights
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 marketAssess the commercial potential of the products in the late-stage pipelineGain insight into opinion leaders' thoughts on the challenges facing the SLE market
ABOUT DATAMONITOR HEALTHCARE 2
About the Immunology and Inflammation (I&I) pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Datamonitor insight into the systemic lupus erythematosus market 3
Contributing experts 4
Related reports 4
Upcoming reports 4
CHAPTER 2 EPIDEMIOLOGY 6
Lupus affects less than 1% of the population in the seven major markets 6
US 10
Datamonitor estimates a conservative SLE patient population in the US 10
Prevalence of lupus in Canada is similar to the US 13
Race and ethnic segmentation influence SLE in the US 14
Race is an important mediator of disease activity in SLE 14
Estimated SLE prevalent population in the US can be split by race 14
Japan 15
EU 16
UK 16
Lupus population split by sex in the UK 16
Lupus population split by race in the UK 17
UK prevalence rates can be applied to Germany 17
Prevalence rates from Spain can be applied to France 18
Italy 18
Lupus population split by sex in Italy 18
Spain 18
Lupus population split by sex in Spain 18
The SLE prevalent population will experience minimal growth over the next decade in the seven major markets 19
Countries of emerging markets represent a large SLE patient population 20
CHAPTER 3 SLE MARKET 22
Drug approvals 22
Prograf (tacrolimus) approved for lupus nephritis in Japan 22
Clinical trial design 23
FDA's recommendations for SLE drug development remain as draft guidance 23
Key challenges in clinical trials for SLE 24
Global opportunities and threats 27
Opportunities 27
High demand for products and level of unmet need provide a significant opportunity in the SLE market 27
Steroid-sparing therapies with improved side-effect profiles are needed 28
Understanding pathogenesis of SLE will help drive drug development 28
Potential for early use of biologics exists in SLE 29
Significant patient population in the emerging markets 30
Threats 30
Comparatively smaller patient population in the seven major markets 30
Lack of clarity from regulatory agencies 31
Difficulty and/or delay in diagnosis 31
Cost to healthcare systems of expensive therapies 32
Potential threat from biosimilars 33
Estimation of the size of the off-label SLE market in 2007 33
Estimation of Rituxan/MabThera costs for the treatment of SLE 34
Cost of Rituxan/MabThera in the seven major markets 34
Size of the SLE population receiving off-label Rituxan/MabThera 35
Diagnosis Value to establish retail sales of key brands 38
CHAPTER 4 PIPELINE DRUGS AND KEY TRIALS 40
Majority of pipeline drugs are being developed for SLE specifically 40
Promising drug candidates in Phase III development 41
Competitive landscape of the late-stage pipeline 45
Estimation of Phase III product launch dates 45
Commercial versus clinical attractiveness of late-stage products 46
Immunosuppressants 47
Prestara/Aslera (prasterone) 47
After two failed Phase III studies, Genelabs secures SPA 47
Strong competition from targeted therapies drives Genelabs to search for late-stage development partner 49
Prestara: Strengths and weaknesses 49
Riquent (abetimus sodium) 50
La Jolla pushes on with another Phase III trial 50
Riquent: Strengths and weaknesses 52
B-cell therapy 53
Atacicept (TAC-Ig) 54
Phase Ib data confirm atacicept's mechanism of action in SLE patients 54
Merck Serono partnership strengthens atacicept's commercial potential 55
Atacicept has entered Phase II/III clinical trials for SLE and lupus nephritis 55
Atacicept: Strengths and weaknesses 57
Rituxan/MabThera (rituximab) 57
Rituxan is already prescribed off-label for SLE 57
Rituxan looks set to achieve first to market status 58
Small studies demonstrate efficacy of Rituxan in SLE 60
FDA raised safety concerns over the use of Rituxan in SLE patients 62
Rituxan/MabThera: Strengths and weaknesses 64
Ocrelizumab 64
Second generation humanized anti-CD20 MAb being developed for SLE 64
Potential for cannibalization of Rituxan/MabThera sales by ocrelizumab 65
Genentech and Biogen Idec embroiled in arbitration over ocrelizumab, which could affect its progress towards commercialization 65
Phase III clinical trials for ocrelizumab in SLE have been initiated 66
Ocrelizumab: Strengths and weaknesses 67
LymphoStat-B (belimumab) 67
Efficacy of belimumab has been demonstrated in Phase II trials by multiple disease activity indices in seropositive SLE patients 68
Phase III trials for belimumab 69
LymphoStat-B: Strengths and weaknesses 71
Epratuzumab 71
Phase III trials have resumed for SLE after regulatory agencies put clinical trials on hold 72
Epratuzumab: Strengths and weaknesses 74
Other cytokines suppression 75
Orencia (abatacept, CTLA4-Ig) 75
Orencia: Strengths and weaknesses 76
Actemra (tocilizumab) 77
Anti-TNF therapy: is there a place in the treatment of SLE? 79
Remicade (infliximab) 80
Enbrel (etanercept) 81
Recently discontinued drugs 82
CellCept (mycophenolate mofetil) 82
CellCept used off-label for systemic lupus erythematosus and is the standard of care in many patients 82
Development of CellCept for lupus nephritis on hold as trial fails to show superiority over Cytoxan 83
Drugs in development for cutaneous lupus erythematosus 85
CNTO-136 85
ASF-1096 85
TRX-1 86
CHAPTER 5 BIBLIOGRAPHY 88
References 88
Websites 94
Datamonitor reports 98
APPENDIX 99
Contributing experts 99
About Datamonitor 100
About Datamonitor Healthcare 100
Datamonitor Healthcare's research and analysis methodologies 101
Datamonitor Healthcare's therapy area capabilities 101
Disclaimer 103
List of Tables
Table 1: SLE population, split by sex, across the seven major markets, 2008 6
Table 2: Key prevalence and incidence studies of systemic lupus erythematosus, 1976-2008 8
Table 3: Estimate of persons with definite systemic lupus erythematosus in the US, split by race and sex, 2005 11
Table 4: Prevalence estimates of systemic lupus erythematosus in California and Pennsylvania, 2000 12
Table 5: Estimation of the systemic lupus erythematosus population in the US using prevalence figures reported by Chakravarty et al. 13
Table 6: Estimate of the systemic lupus erythematosus prevalent population in Canada, 2008 14
Table 7: Systemic lupus erythematosus prevalent population, split by race, in the US, 2008 15
Table 8: Systemic lupus erythematosus prevalent population, split by race, in the UK, 2008 17
Table 9: The estimated systemic lupus erythematosus prevalent population, split by sex, in the seven major markets, 2008-2018 19
Table 10: The estimated systemic lupus erythematosus prevalent population in the emerging markets of China, India and Mexico, 2008 21
Table 11: Phase III trial results for Prograf (tacrolimus) in lupus nephritis 22
Table 12: Cost of Rituxan/MabThera in the major 5EU markets and the US for the treatment of systemic lupus erythematosus 34
Table 13: Estimation of the off-label sales of Rituxan/MabThera in the treatment of systemic lupus erythematosus, 2008 36
Table 14: Datamonitor's definition of systemic lupus erythematosus 38
Table 15: Estimated sales of the main drugs used in the treatment of systemic lupus erythematosus in the seven major markets, ($000s), 2007 39
Table 16: Products in development for lupus indications, 2008 43
Table 17: Summary of Phase III clinical trials for Prestara (prasterone), 1994-2004 48
Table 18: Overview of small-scale studies involving Rituxan/MabThera (rituximab) for lupus indications 60
Table 19: Overview of the Phase III clinical trial of ocrelizumab for systemic lupus erythematosus, 2008 66
Table 20: LymphoStat-B (belimumab): Key abstracts from ACR/ARHP Scientific Meetings 2006-07 68
Table 21: LymphoStat-B: Key clinical trials for lupus indications, 2008 70
Table 22: Orencia (abatacept): Key clinical trials for lupus indications, 2008 75
List of Figures
Figure 1: Potential strategies for improved clinical trial design or systemic lupus erythematosus 25
Figure 2: Opportunities and threats in the systemic lupus erythematosus market, 2008 27
Figure 3: Summary of the method used to estimate the sales of Rituxan/MabThera for systemic lupus erythematosus in the 6MM, 2008 37
Figure 4: Number of pipeline drugs in development split by lupus indication, 2008 41
Figure 5: Number of pipeline drugs in development for lupus erythematosus indications split by clinical phase, 2008 42
Figure 6: Timeline for estimated Phase III product launches for systemic lupus erythematosus, 2008-2016 45
Figure 7: Commercial and clinical assessment of key late-stage pipeline therapies for systemic lupus erythematosus, 2008 46
Figure 8: Prestara: Strengths and weaknesses for SLE, 2008 50
Figure 9: Riquent: Strengths and weaknesses for SLE, 2008 53
Figure 10: Atacicept: Strengths and weaknesses for SLE, 2008 57
Figure 11: Historical time line of approval of Rituxan for rheumatoid arthritis and estimation of approval timing for SLE indication 60
Figure 12: Rituxan/MabThera: Strengths and weaknesses for SLE, 2008 64
Figure 13: Ocrelizumab: Strengths and weaknesses for SLE, 2008 67
Figure 14: LymphoStat-B: Strengths and weaknesses for SLE, 2008 71
Figure 15: Epratuzumab: Strengths and weaknesses for SLE, 2008 74
Figure 16: Orencia: Strengths and weaknesses for SLE, 2008 77
