1 Table of Contents

1 Table of Contents 2
1.1 List of Tables 7
1.2 List of Figures 8

2 Sepsis and Septic Shock: Executive Summary 10
2.1 Global Sepsis and Septic Shock Market to Experience Strong Growth on Launch of First-in-Class Pipeline Products 11
2.2 Developers Must Leverage Innovative R&D Strategies to Target Appropriate Patients and Achieve Sustained Commercial Success 13
2.3 A High Level of Unmet Need Persists in the Sepsis and Septic Shock Marketplace 13
2.4 Opportunities Remain for Current and Future Players to Develop Therapies Targeting Sepsis-Specific Pathophysiology 14
2.5 Immunomodulating Therapies Poised to Transform Sepsis and Septic Shock Market, but Missing Biomarkers Will Limit Their Utility 15
2.6 What Do Physicians Think? 17

3 Introduction 20
3.1 Catalyst 20
3.2 Related Reports 21
3.3 Upcoming Related Reports 21

4 Disease Overview 22
4.1 Etiology and Pathophysiology 22
4.1.1 Etiology 22
4.1.2 Pathophysiology 34
4.2 Classification or Staging Systems 44
4.3 Symptoms 46
4.4 Prognosis 46
4.5 Quality of Life 47

5 Epidemiology 48
5.1 Disease Background 48
5.2 Risk Factors and Comorbidities 49
5.3 Global and Historical Trends 50
5.4 Forecast Methodology 52
5.4.1 Sources 52
5.4.2 Forecast Assumptions and Methods 60
5.4.3 Diagnosed Incident Cases of Sepsis 60
5.4.4 Diagnosed Incident Cases of Septic Shock 64
5.4.5 Diagnosed Incident Cases of Sepsis/Septic Shock by Causative Agent 66
5.4.6 Organ Dysfunction among Diagnosed Incident Cases of Sepsis 69
5.4.7 Organ Dysfunction among Diagnosed Incident Cases of Septic Shock 72
5.4.8 Sepsis In-Hospital Mortality Cases 74
5.4.9 Septic Shock In-Hospital Mortality Cases 77
5.5 Epidemiological Forecast for Sepsis and Septic Shock (2016-2026) 80
5.5.1 Diagnosed Incident Cases of Sepsis 80
5.5.2 Age-Specific Diagnosed Incident Cases of Sepsis 81
5.5.3 Sex-Specific Diagnosed Incident Cases of Sepsis 82
5.5.4 Diagnosed Incident Cases of Sepsis by Causative Agent 83
5.5.5 Organ Dysfunction among Diagnosed Incident Cases of Sepsis 84
5.5.6 Sepsis In-Hospital Mortality Cases 84
5.5.7 Age-Specific In-Hospital Mortality Cases of Sepsis 85
5.5.8 Diagnosed Incident Cases of Septic Shock 86
5.5.9 Age-Specific Diagnosed Incident Cases of Septic Shock 87
5.5.10 Sex-Specific Diagnosed Incident Cases of Septic Shock 88
5.5.11 Diagnosed Incident Cases of Septic Shock by Causative Agent 89
5.5.12 Organ Dysfunction among Diagnosed Incident Cases of Septic Shock 90
5.5.13 Septic Shock In-Hospital Mortality Cases 91
5.5.14 Age-Specific In-Hospital Mortality Cases of Septic Shock 92
5.6 Discussion 93
5.6.1 Epidemiological Forecast Insight 93
5.6.2 Limitations of Alysis 95
5.6.3 Strengths of Alysis 95

6 Current Treatment Options 97
6.1 Overview 97
6.2 Diagnosis and Treatment 99
6.2.1 Diagnosis 99
6.2.2 Treatment Guidelines 105
6.3 Clinical Practice 107
6.3.1 Overview 107
6.3.2 Surviving Sepsis Campaign Bundles 108
6.3.3 Country Differences 109
6.4 Infection Control - Antibiotics and other Anti-infectives 111
6.4.1 Overview 111
6.4.2 Timing of Antibiotic Therapy 113
6.4.3 Dosing of Antibiotic Therapy 115
6.4.4 Antibiotic Resistance 116
6.4.5 Other Therapies - Antivirals, Antifungals, and Antiparasitics 117
6.5 Supportive Treatment Options for Sepsis and Septic Shock 118
6.5.1 Overview 118
6.5.2 Fluid Resuscitation, Vasopressors, Dobutamine, and Blood Transfusion 119
6.5.3 Mechanical Ventilation and Hemodialysis 121
6.6 Other Therapeutic Approaches to Sepsis and Septic Shock 122

7 Unmet Needs Assessment and Opportunity Alysis 124
7.1 Overview 124
7.2 Improved Biomarkers to Guide Treatment Decisions and Support Drug Development 125
7.2.1 Unmet Need 125
7.2.2 Gap Alysis 128
7.2.3 Opportunity 129
7.3 Novel Therapeutic Interventions Targeting Sepsis Pathophysiology 130
7.3.1 Unmet Need 130
7.3.2 Gap Alysis 131
7.3.3 Opportunity 133
7.4 Enhancing Effectiveness of Currently Available Interventions to Help Improve Clinical Outcomes 134
7.4.1 Unmet Need 134
7.4.2 Gap Alysis 136
7.4.3 Opportunity 137
7.5 Streamlined Regulatory Framework to Stimulate Clinical Research and Drug Development 138
7.5.1 Unmet Need 138
7.5.2 Gap Alysis 139
7.5.3 Opportunity 140
7.6 More reliable animal models to facilitate effective screening of lead candidates 141
7.6.1 Unmet Need 141
7.6.2 Gap Alysis 143
7.6.3 Opportunity 144
7.7 Improved Awareness among Healthcare Workers and the Public 144
7.7.1 Unmet Need 144
7.7.2 Gap Alysis 145
7.7.3 Opportunity 146

8 Research and Development Strategies 147
8.1 Overview 147
8.1.1 New SEPSIS-3 Consensus Definition to Guide Future R&D Efforts 150
8.1.2 Immuno-stimulatory Drugs for Late-Step Intervention 151
8.1.3 Other Specific Development Strategies 156
8.1.4 Anti-inflammatory Drugs for Early Intervention (IFX-1, Toraymyxin) 158
8.2 Clinical Trial Design 161
8.2.1 Overview 161
8.2.2 Traditiol Clinical Trial Design 162
8.2.3 Adaptive Clinical Trial Design 163
8.2.4 Participant Enrolment Criteria 166
8.2.5 Endpoints 170

9 Pipeline Assessment 172
9.1 Overview 172
9.2 Promising Drugs in Clinical Development 173
9.2.1 Selepressin 176
9.2.2 Thrombomodulin (ART-123) 181
9.2.3 recAP 190
9.2.4 Traumakine (Recombint Human IFN-?-1a) 195
9.2.5 BMS-936559 198
9.2.6 CYT107 203
9.2.7 Cefiderocol 208
9.2.8 Toraymyxin (PMX-20R) 210
9.2.9 CytoSorb 218
9.3 Other Innovative Early-Stage Approaches 221
9.3.1 IFX-1 221
9.3.2 LB1148 (tranexamic acid) 222
9.3.3 ALT-836 223
9.3.4 Salvecin 226
9.3.5 Opdivo (nivolumab) 226
9.3.6 Adrecizumab 227
9.3.7 LGT-209 228
9.4 Other Drugs in Development 229
9.4.1 Cx-611 229
9.4.2 HU-003 230
9.4.3 Pooled Human Plasma 230
9.4.4 BMS-986189 230
9.4.5 Motrem 231

10 Pipeline Valuation Alysis 232
10.1 Clinical Benchmark of Key Pipeline Drugs 232
10.2 Commercial Benchmark of Key Pipeline Drugs 235
10.3 Competitive Assessment 238
10.4 Top-Line 10-Year Forecast 242
10.4.1 US 248
10.4.2 5EU 253
10.4.3 Japan 258

11 Appendix 263
11.1 Bibliography 263
11.2 Abbreviations 291
11.3 Methodology 297
11.4 Forecasting Methodology 297
11.4.1 Diagnosed Sepsis and Septic Shock Patients 297
11.4.2 Percent Drug-Treated Patients 298
11.4.3 Drugs Included in Each Therapeutic Class 298
11.4.4 Launch and Patent Expiry Dates 299
11.4.5 General Pricing Assumptions 300
11.4.6 Individual Drug Assumptions 301
11.4.7 Generic Erosion 308
11.4.8 Pricing of Pipeline Agents 308
11.5 Primary Research - KOLsInterviewed for this Report 311
11.6 Primary Research - Prescriber Survey 313
11.7 About the Authors 314
11.7.1 Alyst 314
11.7.2 Therapy Area Director 314
11.7.3 Epidemiologist 315
11.7.4 Maging Epidemiologists 315
11.7.5 Global Director of Therapy Alysis and Epidemiology 316
11.7.6 Global Head and EVP of Healthcare Operations and Strategy 317
11.8 About GlobalData 317
11.9 Contact Us 317
11.10 Disclaimer 318