The Systemic Lupus Erythematosus (SLE) drug market is currently under-served by non-generic, targeted therapies. Whilst the only Food and Drug Administration (FDA)-approved biologic, Benlysta (belimumab), generated sales of $111m in 2012, there is little evidence that the drug’s performance is significantly superior to other B-cell targeted therapies such as Rituxan (rituximab), which is often used off-license to treat refractory SLE patients. Therapeutics entering the market therefore do not face the staggering level of competition from currently marketed programs as in other markets such as the Rheumatoid Arthritis (RA) market. Emerging market entrants that appear to offer significant therapeutic benefits are likely to cause dramatic changes to the market landscape.

A growing understanding of the signaling pathways underlying SLE pathophysiology including, but not limited to, B cells, T cells and intracellular kinases, is translating into a higher number of novel, and more importantly, first-in-class targeted therapeutics entering the developmental pipeline. In particular, a high level of investment in the development of cytokine-blocking strategies is evident, as therapies targeting the interferon pathway are relatively common in the pipeline.

Scope

• The report analyzes the market for SLE therapeutics and the pipeline products in that market, with particular emphasis on first-in-class programs.
• A brief introduction to SLE, including symptoms, pathophysiology, disease scoring indices and overview of pharmacotherapy
• In-depth analysis and literature review on marketed products, including analyses of their safety, efficacy, treatment patterns and strengths/weaknesses, based on published clinical trials, as well as a reference table of drugs in terms of safety and efficacy
• Overview of how innovation products are contributing to the market for SLE therapeutics
• Comprehensive review of the pipeline for first-in-class therapies, which is analyzed on the basis of phase distribution, molecule types and molecular targets, as well as administration routes
• The changing molecular target landscape between market and pipeline, and, in particular, focal points of innovation
• First-in-class molecular targets, highlighting early-stage programs for which clinical utility has yet to be evaluated, as well as an in-depth literature review on novel molecular targets

Reasons to buy

The report will assist the business development strategies of companies that wish to develop novel therapies with improved benefits to existing treatments. It will also be of interest to companies seeking to expand their pipeline portfolio through licensing agreements and co-development deals. Primarily, the report will allow clients to identify and understand market opportunities and the emerging competitive environment. It will also allow you to –

• Understand the SLE pipeline and the factors which indicate that it is becoming more innovative
• Understand the overall focal shifts in therapeutic molecular targets for the treatment of SLE
• Understand the distribution of the pipeline programs by phase of development, molecule type and molecular target
• Identify the list of first-in-class programs that are potentially open to deal-making opportunities
• Understand the first-in-class developmental programs and gauge the current clinical effectiveness based on animal models

Table of Contents

1 Table of Contents 4

1.1 List of Tables 5

1.2 List of Figures 6

2 Introduction 7

2.1 The Case for Innovation in Systemic Lupus Erythematosus 7

2.2 Growing Opportunities for Biologic Products 7

2.3 Diversification of Molecular Targets 7

2.4 Innovative First-in-Class Product Developments Remain Attractive 8

2.5 Changes in the Clinical and Commercial Environment to be More Favorable to Products Targeting Niche Patient Populations and Indications 8

2.6 Sustained Innovation 8

3 Systemic Lupus Erythematosus 9

3.1 Disease Overview 9

3.2 Epidemiology 9

3.3 Disease Pathophysiology 10

3.4 Disease Symptoms 10

3.5 Environmental and Genetic Predisposition 11

3.6 Diagnosis 11

3.7 Disease Severity Assessments 12

3.7.1 PGA 12

3.7.2 SLEDAI 12

3.7.3 BILAG 13

3.7.4 SRI 13

3.8 Lupus Nephritis 13

3.9 Pharmacotherapy Algorithm 14

4 Clinical and Commercial Landscape 16

4.1 Corticosteroids 16

4.2 Antimalarials 16

4.3 Cytotoxic Chemotherapy 16

4.4 Biologics 17

4.4.1 Benlysta (belimumab) 17

4.5 Comparative Strengths and Weaknesses of Traditional Therapeutics 19

4.5.1 Corticosteroids vs Cytotoxic Therapeutics 19

4.5.2 Comparison of Immunosuppressants: Cyclosporine vs Azathioprine or Cyclophosphamide 21

4.5.3 Cyclophosphamide vs Azathioprine 23

4.5.4 Cyclophosphamide vs Mycophenolate Mofetil 23

4.5.5 Mycophenolate Mofetil vs Azathioprine 23

4.5.6 Biologics vs Immunosuppressants 25

4.6 Current Unmet Needs in the Systemic Lupus Erythematosus Market 27

5 Assessment of Pipeline Product Innovation 28

5.1 Overview of Pipeline Products for Systemic Lupus Erythematosus 28

5.2 Frequently Targeted Molecular Target Families 29

5.3 Comparative Distribution of Programs between the Systemic Lupus Erythematosus Market and Pipeline by Therapeutic Target Family 30

5.4 Comparative Efficacy and Safety of Pipeline Programs 31

5.5 Comparative Distribution of Programs with First-in-Class and Established Targets 33

5.6 Pipeline Programs Targeting Established Molecular Targets 35

5.7 First-in-class Pipeline Programs with Novel Molecular Targets 37

6 First-in-Class Target and Pipeline Program Evaluation 39

6.1 Cytokines and Receptors 39

6.1.1 Pipeline Programs Targeting IFN-α 39

6.1.2 Pipeline Programs Targeting CD74 43

6.1.3 Pipeline Programs Targeting B7 Related Protein 44

6.1.4 Pipeline Programs Targeting IL-21 46

6.1.5 Pipeline Programs Targeting IL-17 49

6.1.6 Pipeline Programs Targeting High Mobility Protein Box 1 51

6.1.7 Pipeline Programs Targeting APRIL 53

6.2 B and T Cell Antigens 55

6.2.1 Pipeline Programs Targeting CD4 55

6.2.2 Pipeline Programs Targeting CD40L 57

6.2.3 Pipeline Programs which Target FcγR2b (CD32b) 60

6.2.4 Pipeline Programs which Target CD19 62

6.2.5 Pipeline Programs which Target CD22 64

6.3 Intracellular Kinase 67

6.3.1 Pipeline Programs which Target Spleen Tyrosine Kinase 67

6.4 Others 70

6.4.1 Pipeline Programs which Target Immunoproteasome subunit 7 (IMP7) 70

6.4.2 Pipeline Programs which Target ILT-7 71

7 Conclusions 72

8 Deals and Strategic Consolidations 74

8.1 Licensing Agreements 74

8.2 Co-development Deals 76

8.2.1 First-in-Class Developmental Programs Not Involved in Co-development Deals or Licensing Deals 78

9 Appendix 79

9.1 References 79

9.2 Abbreviations 88

9.3 Methodology 89

9.4 Contact Us 89

9.5 Disclaimer 89

List of Tables

Table 1: SLEDAI Index 12

Table 2: Classification of Lupus Nephritis 14

Table 3: Pipeline, Global, First-in-class Modulators of B7-Related Protein, Scientific Assessment 44

Table 4: Pipeline, Global, First-in-Class Modulators of IL-17, Scientific Assessment 49

Table 5: Pipeline, Global, First-in-class Modulators of APRIL, Scientific Assessment 53

Table 6: Pipeline, Global, First-in-class Modulators of CD4, Scientific Assessment 55

Table 7: Pipeline, Global, First-in-Class Modulators of FcγR2b, Scientific Assessment 60

Table 8: Pipeline, Global, First-in-Class Modulators of CD19, Scientific Assessment 62

Table 9: Pipeline, Global, First-in-Class Modulators of CD22, Scientific Assessment 65

Table 10: Pipeline, Global, First-in-Class Modulators of Immunoproteasome Subunit 7, Scientific Assessment 70

Table 11: Pipeline, Global, First-in-Class Modulators of Immunoproteasome Subunit 7, Pipeline Development 71

Table 12: Pipeline, Global, First-in-Class Modulators of Immunoglobulin-Like Transcript 7, Pipeline Development 71

List of Figures

Figure 1: SLE, Treatment Algorithm 14

Figure 2: Systemic Lupus Erythematosus, Global, Marketed Products 18

Figure 3: Systemic Lupus Erythematosus, Global, Comparative Efficacy and Safety of Marketed Products 19

Figure 4: Systemic Lupus Erythematosus, Global, Marketed Products, Comparative Efficacy and Safety 20

Figure 5: Systemic Lupus Erythematosus, Global, Marketed Products, Comparative Efficacy and Safety 22

Figure 6: Systemic Lupus Erythematosus, Global, Marketed Products, Comparative Efficacy and Safety 24

Figure 7: Systemic Lupus Erythematosus, Global, Comparative Efficacy and Safety 26

Figure 8: Systemic Lupus Erythematosus, Global Pipeline Overview 28

Figure 9: Systemic Lupus Erythematosus, Global, Pipeline and Marketed Products 30

Figure 10: Systemic Lupus Erythematosus, Global, Comparative Efficacy and Safety of Pipeline Programs Relative to Benlysta (belimumab) 32

Figure 11: Systemic Lupus Erythematosus, Global, Pipeline, First-in-class Products 34

Figure 12: Systemic Lupus Erythematosus, Global, Pipeline, Programs with Established Molecule Targets 36

Figure 13: Systemic Lupus Erythematosus, Global, Pipeline, First-in-class Programs 38

Figure 14: Pipeline, Global, First-in-Class IFN-α Inhibitors, Scientific assessment 41

Figure 15: Pipeline, Global, First-in-Class IFN-α Inhibitors, Pipeline Development 42

Figure 16: Pipeline, Global, First-in-Class CD74 Inhibitors, Pipeline Development 43

Figure 17: Pipeline, Global, First-in-Class Modulators of B7-Related Protein, Pipeline Development 45

Figure 18: Pipeline, Global, First-in-class modulators of IL-21, Scientific Assessment 47

Figure 19: Pipeline, Global, First-in-class Modulators of IL-21, Pipeline Development 48

Figure 20: Pipeline, Global, First-in-Class Modulators of IL-17 , Pipeline Development 50

Figure 21: Pipeline, Global, First-in-Class High Mobility Box Protein 1 Inhibitors, Pipeline Development 52

Figure 22: Pipeline, Global, First-in-class Modulators of APRIL, Pipeline Development 54

Figure 23: Pipeline, Global, First-in-class Modulators of CD4, Pipeline Development 56

Figure 24: Pipeline, Global, First-in-Class Modulators of CD40L, Scientific Assessment 58

Figure 25: Pipeline, Global, First-in-Class Modulators of CD40L, Pipeline Development 59

Figure 26: Pipeline, Global, First-in-Class Modulators of FcγR2b, Pipeline Development 61

Figure 27: Pipeline, Global, First-in-Class Modulators of CD19, Pipeline Development 63

Figure 28: Pipeline, Global, First-in-Class Modulators of CD22, Pipeline Development 66

Figure 29: Pipeline, Global, First-in-Class Modulators of Spleen Tyrosine Kinase, Scientific Assessment 68

Figure 30: Pipeline, Global, First-in-Class modulators of Spleen Tyrosine Kinase, Pipeline Development 69

Figure 31: Systemic Lupus Erythematosus, Global, Licensing Agreements, 2006-2013 (October) 75

Figure 32: Systemic Lupus Erythematosus, Global, Co-development deals, 2006-2013 (October) 77

Figure 33: Systemic Lupus Erythematosus, Global, First in-Class Programs Not Involved in Co-development or Licensing Deals 78