Summary
Rheumatoid Arthritis (RA) is a chronic, progressive and currently incurable autoimmune disease that primarily affects the joints. It is characterized by synovial inflammation and gradual bone erosion over many years. Disease progression results in stiffness and pain, especially in the hands and feet, which hinders mobility. Without treatment, the disease leads to joint destruction and disability.
The chronic nature of the disease, which requires ongoing treatment, and the relatively high annual cost of therapy (ACoT) have made RA treatment a highly lucrative market. The RA therapeutic market has become very competitive due to the high number of new drug approvals. Competition is fierce, particularly among TNF-α inhibitors, which dominate the treatment market for RA patients who are refractory to traditional disease-modifying anti-rheumatic drugs (DMARD).
Despite this, 30% of RA patients fail to attain a clinical response when treated with TNF-α inhibitors. However, other targeted programs, as well as newly marketed small-molecule DMARDs such as the Janus kinase (JAK) inhibitor Xeljanz (tofacitinib), have the potential to replace ineffective TNF-α inhibitors. Recently published study results of Xeljanz have shown a significant reduction in the risk of developing cardiac diseases such as heart attack and stroke in patients with RA.
Despite the superior efficacy of recently marketed therapies over traditional DMARD therapies, there is a need to improve safety in the therapeutic landscape. Elevated rates of infection are a frequent consequence of the immunosuppression involved in treatments, but this is required to suppress the autoimmune responses responsible for the symptoms of the condition.
As a result, these biological therapies are not recommended to patients who are susceptible to infection. In addition, there is a need to create biologics with more convenient and less invasive drug-delivery methods, as all existing therapies are administered subcutaneously or intravenously.
These routes of administration are frequently associated with pain, rash, and allergic reactions at the injection or infusion site and, in the case of infusion, flu-like illness, fever, chills, nausea, and headache. Therefore convenient and safe administration without significant compromise of therapy efficacy remains an unmet need.
Although the recently approved drug Xeljanz is an orally administered small-molecule drug, indicated as a second-line treatment for RA patients who have not shown an adequate response to methotrexate, and as a third-line therapy for patients who have not responded sufficiently to biologics, it carries a black-box warning in the US due to the safety issues of serious infections and malignancy.
Scope
-The current Asia-Pacific RA market contains novel products, including sirukumab, an anti-IL-6 human mAb; Peficitinib, Upadacitinib and Filgotinib, which are JAK1 inhibitors; Olokizumab, an anti-IL-6 humanized IgG4 mAb; and RCT-18, a recombinant human B-lymphocyte stimulating factor (BLyS) receptor-antibody fusion protein.
- What are the competitive advantages of the existing novel drugs?
- There are over 480 active pipeline molecules, and most of the late-stage investigational drug candidates feature improved dosing regimens and administration routes in comparison to currently marketed products and combination therapies.
- Which classes of novel drugs are most prominent in the pipeline?
- What is the potential for pipeline products to address unmet needs in the RA market?
- Analysis of clinical trials since 2006 identified that the failure rates of RA molecules were highest in Phase II, at 72.6%, with the overall attrition rate for RA standing at 94.6%.
- How do failure rates vary by stage of development, molecule type, and molecular target?
- How do other factors, such as average trial duration and trial size, influence the costs and risks associated with product development?
- Over the 2016-2023 forecast period, the Asia-Pacific RA therapeutics market is expected to increase in value at a compound annual growth rate of 8.2%, from $5.6 billion to over $9.7 billion.
- Which markets make the most significant contribution to the current market size?
- What are the epidemiology trends in these markets?
- Will new market entrants lead to substantial changes in annual therapy costs?
- How will different treatment usage patterns impact growth in the five assessed Asia-Pacific markets?
- A rising RA prevalence population and the uptake of newer therapies will lead to significant market growth over the forecast period, despite the launch of biosimilars of blockbuster anti-TNFs.
- Will the launch of biosimilars or emerging pipeline molecules threaten the commercial success of existing drugs?
- Licensing deals are the most common form of strategic alliance in the RA therapeutics market, with deal values ranging from under $10m to over $1 billion.
- How do deal frequency and value compare between target families and molecule types?
- What were the terms and conditions of key licensing deals?
Reasons to buy
- Understand the clinical context of RA by considering epidemiology, symptoms, etiology and pathophysiology, diagnosis, prognosis, treatment guidelines and options, and biologic registries.
- Identify the therapeutic strategies, products, and companies that dominate the current marketed products landscape and recognize gaps and areas of unmet need.
- Identify key pipeline trends in terms of molecule type, administration route, molecular target, and novelty.
- Consider market opportunities and potential risks by examining trends in RA clinical trial size, duration, and failure rate by stage of development, molecule type, and molecular target.
- Recognize the late-stage pipeline molecules that have demonstrated strong therapeutic potential in RA by examining clinical trial data and multi-scenario product forecast projections.
- Compare treatment usage patterns, annual therapy costs, and market growth projections for India, China, Australia, Japan and South Korea.
- Discover trends in licensing and co-development deals concerning RA products and identify the major strategic consolidations that have shaped the commercial landscape.
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1 Table of Contents
1 Table of Contents 4
1.1 List of Tables 7
1.2 List of Figures 7
2 Introduction 9
2.1 Disease Introduction 9
2.2 Epidemiology 10
2.3 Symptoms 10
2.4 Etiology and Pathophysiology 11
2.5 Diagnosis 12
2.5.1 Physical Examination 12
2.5.2 Blood Tests 12
2.5.3 1987 Rheumatoid Arthritis Classification 13
2.5.4 2010 ACR-EULAR Classification Criteria for Rheumatoid Arthritis 13
2.6 Prognosis 14
2.7 Treatment Guidelines and Options 14
2.7.1 Pharmacological 16
2.7.2 Methotrexate 16
2.7.3 Hydroxychloroquine 17
2.7.4 Leflunomide 17
2.7.5 Sulfasalazine 17
2.7.6 Cyclosporine 17
2.7.7 Xeljanz (tofacitinib) 17
2.7.8 Other Non-biologics 18
2.7.9 Biologic Disease-Modifying Anti-rheumatic Drugs 18
2.7.10 Disease Scoring Methods for Measuring Treatment Efficacy 20
2.8 Co-morbidities and Complications 21
3 Marketed Products 22
3.1 Overview 22
3.2 Small-Molecule Disease-Modifying Anti-rheumatic Drugs 22
3.2.1 Methotrexate-Based Products 22
3.2.2 Xeljanz (tofacitinib) - Pfizer 23
3.3 Biologic Disease-Modifying Anti-rheumatic Drugs 25
3.3.1 Remicade (infliximab) - Johnson & Johnson 25
3.3.2 Humira (adalimumab) - AbbVie 25
3.3.3 Enbrel (etanercept) - Amgen 26
3.3.4 Rituxan/MabThera (rituximab) - Biogen Idec and Genentech 27
3.3.5 Orencia (abatacept) - Bristol-Myers Squibb 28
3.3.6 Simponi (golimumab) - Johnson & Johnson, Merck 28
3.3.7 Cimzia (certolizumab pegol) - UCB 29
3.3.8 Actemra (tocilizumab) - Roche 30
3.3.9 Olumiant (baricitinib) - Eli Lilly 31
3.3.10 Kevzara (Sarilumab) - Regeneron/Sanofi 33
3.3.11 Prolia (denosumab) - Amgen/Daiichi Sankyo 35
3.4 Comparative Efficacy and Safety of Marketed Products 36
3.4.1 Conventional Synthetic Disease Modifying Anti-rheumatic Drugs (csDMARDs) 36
3.4.2 Anti-TNF-α Biologic Disease Modifying Anti-rheumatic Drugs (bDMARDs) 37
3.4.3 Non-anti-TNF-α Biologic Disease Modifying Anti-rheumatic Drugs 39
3.4.4 Targeted Synthetic Disease Modifying Anti-rheumatic Drugs 40
4 Product Pipeline 42
4.1 Overview 42
4.2 Pipeline Distribution by Phase of Development, Molecule Type, Route of Administration and Novelty 43
4.3 Pipeline Distribution by Molecular Target 45
4.4 Promising Pipeline Candidates 48
4.4.1 Sirukumab - Johnson & Johnson 48
4.4.2 Peficitinib - Astellas 50
4.4.3 Upadacitinib - AbbVie 52
4.4.4 Filgotinib - Galapagos 55
4.4.5 Olokizumab - R-Pharm 58
4.4.6 RCT-18 - Yantai RC-Pharma 59
4.5 Comparative Efficacy and Safety of Pipeline Products 59
4.6 Product Competitiveness Framework 61
5 Clinical Trial Analysis 63
5.1 Failure Rate 63
5.1.1 Overall Failure Rate 63
5.1.2 Failure Rate by Phase and Molecule Type 65
5.1.3 Failure Rate by Phase and Molecular Target 66
5.2 Clinical Trial Duration 67
5.2.1 Clinical Trial Duration by Molecule Type 67
5.2.2 Clinical Trial Duration by Molecular Target 68
5.3 Clinical Trial Size 69
5.3.1 Patient Enrollment per Product by Molecule Type, Molecular Target and Stage of Development 69
5.3.2 Patient Enrollment per Trial by Molecule Type, Molecular Target and Stage of Development 70
5.4 Summary of Clinical Trial Metrics 72
6 Multi-Scenario Forecast 74
6.1 Geographical Markets 74
6.2 APAC Markets 74
6.3 India 77
6.3.1 Treatment Usage Patterns 77
6.3.2 Annual Cost of Therapy 77
6.3.3 Market Size 78
6.4 China 79
6.4.1 Treatment Usage Patterns 79
6.4.2 Annual Cost of Therapy 80
6.4.3 Market Size 81
6.5 Australia 82
6.5.1 Treatment Usage Patterns 82
6.5.2 Annual Cost of Therapy 83
6.5.3 Market Size 84
6.6 South Korea 85
6.6.1 Treatment Usage Patterns 85
6.6.2 Annual Cost of Therapy 86
6.6.3 Market Size 87
6.7 Japan 88
6.7.1 Treatment Usage Patterns 88
6.7.2 Annual Cost of Therapy 89
6.7.3 Market Size 90
7 Market Dynamics (Drivers and Barriers) of RA Therapeutics Market 92
7.1 Drivers 92
7.1.1 Rising Prevalence in an Aging Population 92
7.1.2 Launch of Novel Drugs: Oral JAK Inhibitors and Novel Biologics 92
7.1.3 Increasing Awareness of RA 92
7.2 Barriers 93
7.2.1 Increasing Use of Complementary and Alternative Medicine 93
7.2.2 Launch of Cheaper Biosimilars 93
7.2.3 Unmet Needs for Efficacious Therapies Diminishing 93
8 Deals and Strategic Consolidations 94
8.1 Licensing Deals 94
8.1.1 Deals by Region and Value 94
8.1.2 Number of Disclosed and Undisclosed Deals by Year, Aggregate Deal Value 96
8.1.3 Deal Value by Stage of Development, Molecule Type and Molecular Target 97
8.1.4 Maruho Enters into Licensing Agreement with 4SC for a Preclinical Compound 99
8.1.5 CSL Enters into Licensing Agreement with Momenta Pharmaceuticals for M230 Preclinical Product Candidate 100
8.1.6 Mylan Enters into Licensing Agreement with Momenta Pharmaceuticals for Biosimilar Candidates 100
8.1.7 Ablynx Enters into a Licensing Deal with AbbVie for the Nanobody ALX-0061 100
8.2 Co-development 103
8.2.1 Deals by Region and Value 103
8.2.2 Number of Disclosed and Undisclosed Deals by Year, Aggregate Deal Value 105
8.2.3 Deal Value by Stage of Development, Molecule Type, and Molecular Target 106
8.2.4 Sanofi Enters into an Agreement with JHL Biotech 109
8.2.5 Gilead Sciences Enters into Co-development Agreement with Galapagos 109
8.2.6 Epirus Enters into an Agreement with Orygen Biotecnologia 109
8.2.7 Dynavax Enters into Co-development Agreement with GlaxoSmithKline 110
9 Appendix 112
9.1 All Pipeline Drugs by Stage of Development 112
9.1.1 Discovery 112
9.1.2 Preclinical 115
9.1.3 Investigational New Drug/Clinical Trial Authorization-Filed 125
9.1.4 Phase I 125
9.1.5 Phase II 128
9.1.6 Phase III 130
9.1.7 Pre-registration 131
9.2 Summary of Multi-scenario Market Forecasts to 2023 131
9.2.1 Asia-Pacific 131
9.2.2 India 132
9.2.3 China 132
9.2.4 Australia 132
9.2.5 South Korea 133
9.2.6 Japan 133
9.3 Bibliography 133
9.4 Abbreviations 141
9.5 Research Methodology 144
9.5.1 Secondary Research 144
9.5.2 Marketed Product Profiles 145
9.5.3 Late-Stage Pipeline Candidates 145
9.5.4 Comparative Efficacy and Safety Heat Map for Marketed and Pipeline Products 145
9.5.5 Product Competitiveness Framework 145
9.5.6 Pipeline Analysis 146
9.5.7 Clinical Trials 146
9.5.8 Clinical trial Endpoint Analysis 146
9.5.9 Forecasting Model 147
9.5.10 Deals Data Analysis 148
9.6 Contact Us 148
9.7 Disclaimer 148
1.1 List of Tables
Table 1: ACR-EULAR Classification Criteria for Rheumatoid Arthritis, 2010 13
Table 2: RA Therapeutics Market, Global, Licensing Deals Valued over $10m, 2006-2017 101
Table 3: RA Therapeutics Market, Global, Co-development Deals Valued over $10m, 2006-2017 110
Table 4: RA Therapeutics Market, Global, All Pipeline Products, Discovery, 2016 112
Table 5: RA Therapeutics Market, Global, All Pipeline Products, Preclinical, 2016 115
Table 6: RA Therapeutics Market, Global, All Pipeline Products, Investigational New Drug, 2016 125
Table 7: RA Therapeutics Market, Global, All Pipeline Products, Phase I, 2016 125
Table 8: RA Therapeutics Market, Global, All Pipeline Products, Phase II, 2016 128
Table 9: RA Therapeutics Market, Global, All Pipeline Products, Phase III, 2016 130
Table 10: RA Therapeutics Market, Global, All Pipeline Products, Pre-registration, 2016 131
Table 11: RA Therapeutics Market, APAC, Market Forecast, 2016-2023 131
Table 12: RA Therapeutics Market, India, Market Forecast, 2016-2023 132
Table 13: RA Therapeutics Market, China, Market Forecast, 2016-2023 132
Table 14: RA Therapeutics Market, Australia, Market Forecast, 2016-2023 132
Table 15: RA Therapeutics Market, South Korea, Market Forecast, 2016-2023 133
Table 16: RA Therapeutics Market, Japan, Market Forecast, 2016-2023 133
1.2 List of Figures
Figure 1: RA Therapeutics Market, Australia, Age-Specific Prevalence (%), 2014-2015 10
Figure 2: American College of Rheumatology Treatment Guidelines, 2015 15
Figure 3: European League Against Rheumatism Treatment Guidelines, 2016 16
Figure 4: RA Therapeutics Market, Comparative Efficacy and Safety Heatmap for Conventional Synthetic Disease Modifying Anti-rheumatic Marketed Products 37
Figure 5: RA Therapeutics Market, Comparative Efficacy and Safety Heatmap for Anti TNF-α Biologic Disease Modifying Anti-rheumatic Marketed Products 39
Figure 6: RA Therapeutics Market, Comparative Efficacy and Safety Heatmap for Non-TNF-α Biologic Disease Modifying Anti-rheumatic Marketed Products 40
Figure 7: RA Therapeutics Market, Comparative Efficacy and Safety Heatmap for Targeted Synthetic Disease Modifying Anti-rheumatic Marketed Products 41
Figure 8: RA Therapeutics Market, Global, Pipeline, 2016 44
Figure 9 RA Therapeutics Market, Global, Pipeline by Molecular Target, 2016 47
Figure 10: RA Therapeutics Market, Global, Pipeline by Molecular Target and Stage of Development, 2016 48
Figure 11: RA Therapeutics Market, APAC, Sirukumab Forecast ($m), 2018-2023 50
Figure 12: RA Therapeutics Market, APAC, Peficitinib Forecast ($m), 2019-2023 52
Figure 13: RA Therapeutics Market, APAC, Upadacitinib Forecast ($m), 2022-2023 55
Figure 14: RA Therapeutics Market, APAC, Filgotinib Forecast ($m), 2020-2023 57
Figure 15: RA Therapeutics Market, Comparative Efficacy and Safety Heatmap for Pipeline Products 60
Figure 16: RA Therapeutics Market, Competitor Matrix for RA Marketed and Pipeline Products, 2017 62
Figure 17: RA Therapeutics Market, Global, Average Clinical Trial Failure Rate (%), 2016 64
Figure 18: RA Therapeutics Market, Global, Clinical Trial Failure Rate by Molecule Type (%), 2006-2016 65
Figure 19: RA Therapeutics Market, Global, Clinical Trial Failure Rate by Molecular Target (%), 2006-2016 66
Figure 20: RA Therapeutics Market, Global, Clinical Trial Size per Product by Stage of Development and Molecule Type, 2006-2016 67
Figure 21: RA Therapeutics Market, Global, Clinical Trial Duration by Molecular Target, 2006-2016 68
Figure 22: RA Therapeutics Market, Global, Clinical Trial Size per Product by Molecule Type, 2006-2016 69
Figure 23: RA Therapeutics Market, Global, Clinical Trial Size per Product by Molecular Target, 2006-2016 70
Figure 24: RA Therapeutics Market, Global, Clinical Trial Size per Trial by Molecular Type, 2006-2016 71
Figure 25: RA Therapeutics Market, Global, Clinical Trial Size per Trial by Molecular Target, 2006-2016 72
Figure 26: RA Therapeutics Market, Comparison of Average Trial Metrics by Phase and Molecule Type 72
Figure 27: RA Therapeutics Market, Comparison of Average Trial Metrics by Phase and Molecular Target 73
Figure 28: RA Therapeutics Market, Asia Pacific, Treatment Usage Patterns (million), 2016-2023 75
Figure 29: RA Therapeutics Market, Asia Pacific, Market Size ($bn), 2016-2023 76
Figure 30: RA Therapeutics Market, India, Treatment Usage Patterns (’000), 2016-2023 77
Figure 31: RA Therapeutics Market, India, Annual Cost of Therapy ($), 2016-2023 78
Figure 32: RA Therapeutics Market, India, Market Size ($m), 2016-2023 79
Figure 33: RA Therapeutics Market, China, Treatment Usage Patterns (‘000), 2016-2023 80
Figure 34: RA Therapeutics Market, China, Annual Cost of Therapy ($), 2016-2023 81
Figure 35: RA Therapeutics Market, China, Market Size ($m), 2016-2023 82
Figure 36: RA Therapeutics Market, Australia, Treatment Usage Patterns (‘000), 2016-2023 83
Figure 37: RA Therapeutics Market, Australia, Annual Cost of Therapy ($), 2016-2023 84
Figure 38: RA Therapeutics Market, Australia, Market Size ($m), 2016-2023 85
Figure 39: RA Therapeutics Market, South Korea, Treatment Usage Patterns (‘000), 2016-2023 86
Figure 40: RA Therapeutics Market, South Korea, Annual Cost of Therapy ($), 2016-2023 87
Figure 41: RA Therapeutics Market, South Korea, Market Size ($m), 2016-2023 88
Figure 42: RA Therapeutics Market, Japan, Treatment Usage Patterns (‘000), 2016-2023 89
Figure 43: RA Therapeutics Market, Japan, Annual Cost of Therapy ($), 2016-2023 90
Figure 44: RA Therapeutics Market, Japan, Market Size ($m), 2016-2023 91
Figure 45: RA Therapeutics Market, Global, Licensing Deals by Region and Value, 2006-2017 95
Figure 46: RA Therapeutics Market, Global, Number of Disclosed and Undisclosed Licensing Deals by Year, Aggregate Deal Value and Aggregate Upfront Payment Value, 2006-2017 96
Figure 47: RA Therapeutics Market, Global, Licensing Deals by Stage of Development, and Deal Value, 2006-2017 97
Figure 48: RA Therapeutics Market, Global, Licensing Deals by Molecule Type and Stage of Development, 2006-2017 98
Figure 49: RA Therapeutics Market, Global, Licensing Deals by Molecular Target and Aggregate Deal Value ($m), 2006-2017 99
Figure 50: RA Therapeutics Market, Global, Co-development Deals by Region and Deal Value, 2006-2017 104
Figure 51: RA Therapeutics Market, Global, Number of Disclosed and Undisclosed Co-development Deals by Year, Aggregate Deal Value and Aggregate Upfront Payment Value, 2006-2017 105
Figure 52: RA Therapeutics Market, Global, Co-development Deals by Stage of Development, and Deal Value, 2006-2016 106
Figure 53: RA Therapeutics Market, Global, Co-development Deals by Molecule Type and Stage of Development, 2006-2017 107
Figure 54: Rheumatoid Arthritis Market, Global, Co-development Deals by Molecular Target, 2006-2017 108
