Published : Jul-2017
No. of Pages : 281
1 Table of Contents 2
1.1 List of Tables 7
1.2 List of Figures 9
2 Executive Summary 10
2.1 Significant Growth Is Projected for the CDI Market from 2016 to 2026 10
2.2 Manufacturers Aiming to Provide Physicians Non-Antibiotic Therapies for Treatment and Prevention of CDI 12
2.3 There Remains Significant Unmet Need for CDI Treatment, in Particular to Reduce CDI Recurrence Rates 13
2.4 Opportunities Exist for Products Proven to be Cost-Effective Versus SOC Antibiotics 14
2.5 An Active Pipeline Poised to Partially Satisfy Unmet Needs for CDI 14
2.6 What do Physicians Think? 16
3 Introduction 18
3.1 Catalyst 18
3.2 Related Reports 18
3.3 Upcoming Related Reports 19
4 Disease Overview 20
4.1 Etiology and Pathophysiology 20
4.1.1 Etiology 20
4.1.2 Pathophysiology 24
4.2 Symptoms 26
4.3 Disease Management 27
4.3.1 Diagnosis 28
4.3.2 Treatment Guidelines 32
4.3.3 Clinical Practice 34
4.3.4 Prevention and Control 37
4.4 Prognosis and Quality of Life 39
5 Epidemiology 41
5.1 Disease Background 41
5.2 Risk Factors and Comorbidities 42
5.3 Global and Historical Trends 44
5.3.1 7MM: Diagnosed Incidence 45
5.3.2 7MM: Diagnosed Incident Cases by Recurrence 46
5.3.3 7MM: Diagnosed Incident Cases by Severity 47
5.4 Forecast Methodology 47
5.4.1 Sources 48
5.4.2 Forecast Assumptions and Methods 51
5.5 Epidemiological Forecast for CDI (2016-2026) 57
5.5.1 Diagnosed Incident Cases of CDI 57
5.5.2 Age-Specific Diagnosed Incident Cases of CDI 58
5.5.3 Sex-Specific Diagnosed Incident Cases of CDI 58
5.5.4 CDI Cases by Recurrence 59
5.5.5 CDI Cases by Severity 61
5.6 Discussion 63
5.6.1 Epidemiological Forecast Insight 63
5.6.2 Limitations of Analysis 65
5.6.3 Strengths of Analysis 65
6 Current Treatment Options 67
6.1 Overview 67
6.2 Product Profiles - Recommended Antibiotic Therapies 68
6.2.1 Metronidazole (numerous brand names) 68
6.2.2 Vancomycin (numerous brand names) 73
6.2.3 Dificid (fidaxomicin) 78
6.3 Product Profiles - Antibodies 85
6.3.1 Zinplava (bezlotoxumab) 85
6.4 Other Antibiotic Therapies 90
6.4.1 Targocid (teicoplanin) 90
6.4.2 Tygacil (tigecycline) 91
6.4.3 Xifaxan (rifaximin) 92
6.5 Non-drug Interventions 92
6.5.1 OpenBiome FMT (stool-bank service) 93
6.5.2 Probiotics 94
6.5.3 Surgical Procedures 95
7 Unmet Needs Assessment and Opportunity Analysis 97
7.1 Overview 97
7.2 Improved Treatment Options for rCDIs 99
7.2.1 Unmet Need 99
7.2.2 Gap Analysis 100
7.2.3 Opportunity 101
7.3 Prophylactic Products to Prevent Primary CDI 103
7.3.1 Unmet Need 103
7.3.2 Gap Analysis 104
7.3.3 Opportunity 106
7.4 More Cost-Effective Treatment Options 107
7.4.1 Unmet Need 107
7.4.2 Gap Analysis 108
7.4.3 Opportunity 108
7.5 Standardize, Streamline, and Confirm the Long-Term Safety of FMT 110
7.5.1 Unmet Need 110
7.5.2 Gap Analysis 111
7.5.3 Opportunity 112
7.6 Reduce CDI Morbidity and Mortality In Vulnerable Patients 114
7.6.1 Unmet Need 114
7.6.2 Gap Analysis 115
7.6.3 Opportunity 115
7.7 Improve Surveillance and Prevent Transmission and Outbreaks 116
7.7.1 Unmet Need 116
7.7.2 Gap Analysis 117
7.7.3 Opportunity 118
7.8 Reduce Misdiagnosis of CDI From Diagnostic Testing 118
7.8.1 Unmet Need 118
7.8.2 Gap Analysis 119
7.8.3 Opportunity 120
8 Research and Development Strategies 121
8.1 Overview 121
8.2 Current Approaches to CDI Product Development 122
8.2.1 Therapeutic Agents 122
8.2.2 Prophylactic Agents 128
8.3 Clinical Trial Design 132
8.3.1 Therapeutic Agents 132
8.3.2 Prophylactic Agents 137
9 Pipeline Assessment 140
9.1 Overview 140
9.2 Promising Products in Clinical Development 141
9.3 Therapeutic Agents - Antibiotics 146
9.3.1 Cadazolid 146
9.3.2 Ridinilazole 151
9.3.3 OPS-2071 156
9.4 Therapeutic Agents - Microbiologics 158
9.4.1 SER-109 (firmacute eubacterial spores, purified suspensions, encapsulated) 159
9.4.2 RBX2660 (microbiota suspension) 164
9.5 Prophylactic Agents - Vaccines 170
9.5.1 ACAM-CDIFF 171
9.5.2 PF-06425090 175
9.5.3 VLA84 180
9.6 Prophylactic Agents - Drugs 185
9.6.1 Ribaxamase 186
9.7 Other Innovative Approaches to CDI Prevention and Treatment 191
9.7.1 Fecal Microbiota Transplant 192
9.7.2 DAV-132 195
9.7.3 Surotomycin 197
9.7.4 Ramoplanin 198
9.7.5 VP20621 (non-toxigenic C. difficile strain M3 spores) 200
9.8 Other Products in Clinical Development 202
10 Pipeline Valuation Analysis 203
10.1 Clinical Benchmark of Key Pipeline Products 203
10.1.1 Therapeutic Agents 203
10.1.2 Prophylactic Agents 204
10.2 Commercial Benchmark of Key Pipeline Products 205
10.2.1 Therapeutic Agents 205
10.2.2 Prophylactic Agents 206
10.3 Competitive Assessment 207
10.3.1 Therapeutic Agents 207
10.3.2 Prophylactic Agents 208
10.4 Top-Line 10-Year Forecast 210
10.4.1 US 215
10.4.2 5EU 218
10.4.3 Japan 221
11 Appendix 224
11.1 Bibliography 224
11.2 Abbreviations 257
11.3 Methodology 260
11.4 Forecasting Methodology 260
11.4.1 Diagnosed CDI Patient Population 260
11.4.2 Target Patient Populations for Prophylaxis 261
11.4.3 Percent Drug-Treated Patients 262
11.4.4 Drugs Included in Each Therapeutic Class 262
11.4.5 Launch and Patent Expiry Dates 263
11.4.6 General Pricing Assumptions 263
11.4.7 Individual Drug Assumptions 265
11.4.8 Pricing of Pipeline Agents 269
11.5 Primary Research - KOLs Interviewed for this Report 272
11.6 Primary Research - Prescriber Survey 276
11.7 About the Authors 277
11.7.1 Analysts 277
11.7.2 Therapy Area Director 277
11.7.3 Epidemiologists 278
11.7.4 Director of Epidemiology 279
11.7.5 Global Director of Therapy Analysis and Epidemiology 279
11.7.6 Global Head and EVP of Healthcare Operations and Strategy 279
11.8 About GlobalData 281
11.9 Contact Us 281
11.10 Disclaimer 281
1.1 List of Tables
Table 1: Clostridium difficile Infections (CDI): Key Metrics in the 7MM 10
Table 2: Antimicrobial Agents that May Induce CDI, CDAD, and Colitis 22
Table 3: The Physiological Effects of C. difficile Toxins A and B 26
Table 4: Symptoms Associated with CDIs 27
Table 5: Summary of Stool Laboratory Diagnostic Testing for C. difficile 32
Table 6: CDI Severity Scoring System and Summary of Recommended Treatments 36
Table 7: Risk Factors and Comorbidities for CDI 43
Table 8: 7MM, Diagnosed Incident Cases of CDI, Ages =18 Years, Both Sexes, N, Select Years 2016-2026 57
Table 9: Product Profile - Metronidazole 70
Table 10: Clinical Successa of Metronidazole versus Vancomycin by CDI Severity 71
Table 11: Summary of AEs Observed In Two Phase III Trials Comparing Metronidazole to Vancomycin 72
Table 12: Metronidazole SWOT Analysis, 2017 73
Table 13: Product Profile - Vancomycin 75
Table 14: Clinical Success of Vancomycin-Treated Subjects in Two Clinical Trials 76
Table 15: Common AEs for Vancomycin in Treating CDADa 77
Table 16: Vancomycin SWOT Analysis, 2017 78
Table 17: Product Profile - Dificid 80
Table 18: Dificid Pivotal Phase III Clinical Trials Response Rates 81
Table 19: Dificid Pivotal Phase III Clinical Trials Sustained Clinical Response at 25 Days After Treatment According to C. difficile Strain 82
Table 20: Selected Adverse Reactions with an Incidence of =2% Reported in Patients Treated with Dificid in Controlled Trials 84
Table 21: Dificid SWOT Analysis, 2017 84
Table 22: Product Profile - Zinplava (bezlotoxumab) 87
Table 23: Clinical Efficacy of Zinplava with Regard to Recurrence Rates in MODIFY I and MODIFY II Clinical Trials 88
Table 24: AEs Associated with Zinplava, Administered Alone or with Actoxumab and Compared to a Placebo Group, as Observed in Both MODIFY I and MODIFY II RCTs 89
Table 25: Zinplava SWOT Analysis, 2017 90
Table 26: Key Products in the CDI Market by Therapeutic Class, 2017 121
Table 27: Clinical Trial Designs for CDI Pipeline Antibiotics 132
Table 28: Clinical Trial Designs for CDI Pipeline Antibodies 134
Table 29: Clinical Trial Designs for CDI Pipeline Microbiologics 135
Table 30: Clinical Trial Designs for CDI Pipeline Vaccines 137
Table 31: Clinical Trial Designs for CDI Pipeline Prophylactic Adjuvant Therapies. 139
Table 32: Promising Products in Clinical Development for CDIs, 2017 144
Table 33: Product Profile - Cadazolid 148
Table 34: Efficacy Results from Cadazolid Phase II Trial - Modified Intent-to-Treat Populationa 149
Table 35: Cadazolid SWOT Analysis, 2017 151
Table 36: Product Profile - Ridinilazole 153
Table 37: Clinical Success of Ridinilazole versus Vancomycin as Observed in the CoDIFy Phase II Trial 154
Table 38: Adverse Effects Observed in Phase I Trials Assessing the Safety Profile of Ridinilazole 155
Table 39: Ridinilazole SWOT Analysis, 2017 156
Table 40: Product Profile - OPS-2071 157
Table 41: OPS-2071 SWOT Analysis, 2017 158
Table 42: Product Profile - SER-109 161
Table 43: Results from Three Clinical Trials Assessing the Efficacy of SER-109 162
Table 44: SER-109 SWOT Analysis, 2017 164
Table 45: Product Profile - RBX2660 166
Table 46: Results from Three Clinical Trials Assessing the Efficacy of RBX2660 168
Table 47: Reported AEs in the PUNCH CD2 Trial for RBX2660 169
Table 48: RBX2660 SWOT Analysis, 2017 170
Table 49: Product Profile - ACAM-CDIFF 172
Table 50: Formulations and Dosing Schedules and Seroconversion Rate for ACAM-CDIFF Phase II Trial 173
Table 51: Adverse Effects Observed in a Phase II Trial Assessing ACAM-CDIFF 174
Table 52: ACAM-CDIFF SWOT Analysis, 2017 175
Table 53: Product Profile - PF-06425090 177
Table 54: Clinical Trials Carried Out to Assess the Safety, Tolerability, and Immunogenicity of PF-06425090 179
Table 55: PF-06425090 SWOT Analysis, 2017 180
Table 56: Product Profile - VLA84 182
Table 57: Seroconversion Rates for VLA84 Observed During a Phase II Trial 183
Table 58: Doses and Dosing Schedules in VLA84 Phase I Triala 184
Table 59: VLA84 SWOT Analysis, 2017 185
Table 60: Product Profile - Ribaxamase 188
Table 61: Adverse Effects Observed in Two Phase I Trials Assessing the Safety Profile of Ribaxamase 190
Table 62: Ribaxamase SWOT Analysis, 2017 191
Table 63: Other Innovative Approaches to CDI Prevention and Treatment, 2017 192
Table 64: Comparison of Results from Published RCTs Investigating the Efficacy of FMT for Treating Recurrent CDI 194
Table 65: Efficacy Results from Surotomycin Phase III Trial 198
Table 66: Efficacy Results from VP20621 Phase III Trial 202
Table 67: Other CDI Products in Development, 2017 202
Table 68: Clinical Benchmark of Key Pipeline Therapeutics - CDIs 204
Table 69: Clinical Benchmark of Key Pipeline Prophylactics - CDIs 205
Table 70: Commercial Benchmark of Key Pipeline Therapeutics - CDIs 206
Table 71: Clinical Benchmark of Key Pipeline Prophylactics - CDIs 207
Table 72: Top-Line Global Sales Forecasts for CDI Therapeutic and Prophylactic Agents, 2016-2026 211
Table 73: Key Events Impacting Sales for CDIs, 2016-2026 214
Table 74: CDI Market - Global Drivers and Barriers, 2016-2026 215
Table 75: Sources Used For Diagnosed CDI Incidence Segmentation in the 7MM 261
Table 76: Sources Used For Prophylaxis Target Patient Populations in the 7MM 262
Table 77: Key Historical and Projected Launch Dates for CDI 263
Table 78: High-Prescribing Physicians (non-KOLs) Surveyed, By Country 276
1.2 List of Figures
Figure 1: Global (7MM) Sales Forecast by Country for CDIs in 2016 and 2026 12
Figure 2: Competitive Assessment of Marketed and Pipeline Therapeutic Products for CDI Benchmarked Against the SOC, Vancomycin 15
Figure 3: Competitive Assessment of Pipeline Prophylactic Products for CDI 16
Figure 4: Examples of C. difficile-Associated Diseases 21
Figure 5: Overview of the Pathogenesis of CDAD 25
Figure 6: CDI Diagnosis Algorithm Recommended by ESCMID Guidelines 30
Figure 7: Overview of International Treatment Algorithm for CDI and CDAD 34
Figure 8: 7MM, Age-Standardized Diagnosed Incidence of CDI, Ages =18 Years, 2016 45
Figure 9: Case Flow Map 48
Figure 10: Sources Used and Not Used in Epidemiological Analysis of CDI Incidence 49
Figure 11: Sources Used and Not Used in Epidemiological Analysis of CDI Recurrences 50
Figure 12: Sources Used and Not Used in Epidemiological Analysis of CDI Severity 51
Figure 13: 7MM, Age-Specific Diagnosed Incident Cases of CDI, Both Sexes, Ages =18 Years, 2016 58
Figure 14: 7MM, Sex-Specific Diagnosed Incident Cases of CDI, Ages =18 Years, 2016 59
Figure 15: 5EU and Japan, CDI Recurrences, Both Sexes, Ages =18 Years, 2016 60
Figure 16: US, CDI Recurrences, Both Sexes, Ages =18 Years, 2016 61
Figure 17: 5EU and Japan, CDI Cases by Severity, Both Sexes, Ages =18 Years, 2016 62
Figure 18: US, CDI Cases by Severity, Both Sexes, Ages =18 Years, 2016 63
Figure 19: Current Treatment Options for CDIs 68
Figure 20: Unmet Need and Opportunity in CDI 98
Figure 21: Promising Pipeline Products In Development for CDIs with Key Clinical Trials, 2017 143
Figure 22: Bullseye Diagram of Products in Clinical Development for CDIs, 2017 145
Figure 23: Key Clinical Trial Progress for CDI Pipeline Antibiotics 146
Figure 24: Key Clinical Trial Progress for CDI Pipeline Microbiologics 158
Figure 25: Key Clinical Trial Progress for CDI Pipeline Vaccines 170
Figure 26: Key Clinical Trial Progress for CDI Pipeline Prophylactic Adjuvants 185
Figure 27: Competitive Assessment of Marketed and Pipeline Therapeutic Products for CDI Benchmarked Against the SOC, Vancomycin 208
Figure 28: Competitive Assessment of Pipeline Prophylactic Products for CDI 209
Figure 29: Global (7MM) Sales Forecast by Country for CDIs in 2016 and 2026 212
Figure 30: Global (7MM) Sales Forecast by Product Class for CDIs in 2026 213
Figure 31: US Sales Forecast By Product Class for CDIs, 2016-2026 216
Figure 32: Therapeutic Sales Forecast by Product for CDIs in the US in 2016 and 2026 217
Figure 33: Prophylactic Sales Forecast by Product for CDIs in the US in 2026 218
Figure 34: 5EU Sales Forecast By Product Class for CDIs, 2016-2026 219
Figure 35: Therapeutic Sales Forecast by Product for CDIs in the 5EU in 2016 and 2026 220
Figure 36: Prophylactic Sales Forecast by Product for CDIs in the 5EU in 2026 221
Figure 37: Japan Sales Forecast By Product Class for CDIs, 2016-2026 222
Figure 38: Therapeutic Sales Forecast by Product for CDIs in Japan in 2016 and 2026 223
