OpportunityAnalyzer: Clostridium difficile Infections (CDI) - Opportunity Analysis and Forecasts to 2024
Summary
Clostridium difficile, a Gram-positive, spore-forming, toxin-producing, non-invasive, anaerobic bacterium, is the causative organism of C. difficile infection (CDI), which is commonly associated with colitis, as well as C. difficile-associated diarrhea (CDAD). CDI onset begins with colonization of the intestinal tract with C. difficile through community-acquired or healthcare-associated means. C. difficile has been identified as a major cause of antibiotic-associated pseudomembranous colitis and diarrhea, with the earliest cases largely attributed to clindamycin. As penicillins and cephalosporins became more widely used throughout the years, their administration also became associated with an increased risk of developing CDAD. Since 2000, CDIs have become more frequent, more severe, more difficult to treat using existing therapies, and more likely to recur than previously described. These realities, along with increasing threat of antibiotic resistance, underscore the importance of developing CDI-specific therapies and bringing them to market.
For the purposes of this report, GlobalData defines the global CDI market to include sales of therapeutic and prophylactic agents aimed at treatment and prevention of CDI and CDAD in patients 18 years and older across the 7MM, which is comprised of the US, 5EU (France, Germany, Italy, Spain, and the UK), and Japan. GlobalData anticipates a major driver of market growth to be the steady increase in uptake of novel CDI-specific antibiotics once they are approved, but the arrival of non-antibiotic products to the market, such as rationally designed microbiologics and vaccines, are poised to make the biggest clinical impact if approved.
Highlights
Key Questions Answered
- Based on interviews with key opinion leaders (KOLs), GlobalData has identified the major unmet needs in the CDI marketplace. Will the leading therapeutic and prophylactic pipeline agents fulfil these unmet needs during the forecast period (2014-2024)?
- What research and development (R&D) strategies will companies leverage to compete in the future CDI marketplace?
- What adjunctive therapies to standard of care (SOC) antibiotics are poised to make a major clinical and commercial impact?
- What clinical and commercial factors are likely to influence CDI product uptake in the US and 5EU (France, Germany, Italy, Spain, and the UK) and Japan (7MM)?
Key Findings
- GlobalData projects CDI therapeutics and prophylactics market in the 7MM to grow from approximately $356m in 2014 to a little over $1.5bn in 2024, at a compound annual growth rate (CAGR) of 15.8%. This growth will be driven by the increased uptake of novel adjunctive therapies to SOC antibiotics, increased use of Mercks first-to-market antibiotic Dificid, and the arrival of ACAM-CDIFF, the worlds first prophylactic vaccine developed by Sanofi Pasteur to prevent primary infections.
- KOLs interviewed by GlobalData were split on the ability of a prophylactic vaccine developer to demonstrate statistically significant prevention of primary infections in a pivotal Phase III study, specifically citing difficulties reliably anticipating CDI transmission in the patient population. Expert consensus was that non-antibiotic approaches, specifically rationally designed microbiologic therapies, have the potential to shift the treatment paradigm for intractable recurrent infections, although antibiotics should remain the main treatment options through 2024.
- GlobalData anticipates that firms will continue to invest in CDI-specific antibiotics development throughout the forecast period, but product differentiation will remain a difficult task due to the high clinical cure rates with current cost-effective generic antibacterials and the superior sustained cure rate exhibited with Mercks Dificid.
Scope
- Overview of CDI, including epidemiology, etiology, pathophysiology, symptoms, diagnosis, and current treatment options.
- Topline CDI therapeutics and prophylactics market revenue from 2014-2024. Annual cost of therapy (ACOT) and major pipeline product sales in this forecast period are included.
- Key topics covered include strategic competitor assessment, market characterization, unmet needs, opportunities, and R&D strategies for the CDI market.
- Pipeline analysis: comprehensive data split across different phases, emerging novel trends under development, synopses of innovative early-stage projects, and detailed analysis of late-stage pipeline products. An interactive clinical and commercial analyzer tool is available.
- Analysis of the current and future market competition in the global CDI market. Insightful review of the key industry drivers, restraints and challenges. Each trend is independently researched to provide qualitative analysis of its implications.
Reasons to buy
The report will enable you to -
- Develop and design your in-licensing and out-licensing strategies through a review of pipeline products and technologies, and by identifying the companies with the most robust pipeline.
- Develop business strategies by understanding the trends shaping and driving the global CDI therapeutic and prophylactic markets.
- Drive revenues by understanding the key trends, innovative products and technologies, market segments, and companies likely to impact the CDI market in the future.
- Formulate effective sales and marketing strategies by understanding the competitive landscape and by analyzing the performance of various competitors.
- Identify emerging players with potentially strong product portfolios and create effective counter-strategies to gain a competitive advantage.
- Organize your sales and marketing efforts by identifying the market categories and segments that present maximum opportunities for consolidations, investments and strategic partnerships.
Table Of Contents
1 Table of Contents 12
1.1 List of Tables 18
1.2 List of Figures 21
2 Introduction 23
2.1 Catalyst 23
2.2 Related Reports 24
2.3 Upcoming Related Reports 25
3 Disease Overview 26
3.1 Etiology and Pathophysiology 26
3.1.1 Etiology 26
3.1.2 Pathophysiology 29
3.2 Risk Factors and Symptoms 32
3.3 Disease Management 34
3.3.1 Diagnosis 36
3.3.2 Treatment Guidelines 38
3.3.3 Clinical Practice 39
3.3.4 Prevention and Control 42
3.4 Prognosis and Quality of Life 43
4 Epidemiology 45
4.1 Disease Background 45
4.2 Risk Factors and Comorbidities 46
4.3 Global Trends 48
4.3.1 7MM: Diagnosed Incidence Rates 50
4.3.2 7MM: Diagnosed Incident Cases by Epidemiological Association 51
4.3.3 7MM: Diagnosed Incident Cases by Recurrence 51
4.4 Forecast Methodology 52
4.4.1 Sources Used 54
4.4.2 Sources Not Used 61
4.4.3 Forecast Assumptions and Methods 63
4.5 Epidemiological Forecast of CDI (2014-2024) 69
4.5.1 Diagnosed Incident Cases of All-CDI 69
4.5.2 Age-Specific Diagnosed Incident Cases of All-CDI 71
4.5.3 Sex-Specific Diagnosed Incident Cases of All-CDI 73
4.5.4 Age-Standardized Diagnosed Incidence Rate of All-CDI 75
4.5.5 Recurrent CDI Cases 76
4.5.6 Diagnosed Incident Cases of All-CDI by Epidemiological Association 78
4.6 Discussion 80
4.6.1 Epidemiological Forecast Insight 80
4.6.2 Limitations of the Analysis 82
4.6.3 Strengths of the Analysis 82
5 Current Treatment Options 83
5.1 Overview 83
5.2 Product Profiles - Recommended Antibiotic Therapies 85
5.2.1 Metronidazole 85
5.2.2 Vancomycin 92
5.2.3 Dificid (fidaxomicin) 97
5.3 Other Antibiotic Therapies 106
5.3.1 Targocid (teicoplanin) 106
5.3.2 Tygacil (tigecycline) 106
5.3.3 Xifaxan (rifaximin) 107
5.4 Other Drug Interventions 108
5.4.1 Immunotherapy 108
5.5 Non-Drug Interventions 108
5.5.1 Fecal Microbiota Transplant 109
5.5.2 Probiotics 112
5.5.3 Surgical Procedures 113
6 Unmet Needs Assessment and Opportunity Analysis 116
6.1 Overview 116
6.2 Improved Treatment Options for Recurrent CDI 119
6.2.1 Unmet Need 119
6.2.2 Gap Analysis 120
6.2.3 Opportunity 123
6.3 Prophylactic Products to Prevent CDI 126
6.3.1 Unmet Need 126
6.3.2 Gap Analysis 127
6.3.3 Opportunity 128
6.4 Standardize, Streamline, and Confirm Long-Term Safety of FMT 129
6.4.1 Unmet Need 129
6.4.2 Gap Analysis 130
6.4.3 Opportunity 131
6.5 Products to Reduce Morbidity and Mortality in Patients with Severe-Complicated CDI 132
6.5.1 Unmet Need 132
6.5.2 Gap Analysis 133
6.5.3 Opportunity 134
6.6 Clinically Proven CDI Risk Criteria and Prediction Models 134
6.6.1 Unmet Need 134
6.6.2 Gap Analysis 135
6.6.3 Opportunity 136
6.7 Improve Surveillance and Prevent Transmission and Outbreaks 137
6.7.1 Unmet Need 137
6.7.2 Gap Analysis 138
6.7.3 Opportunity 139
7 Research and Development Strategies 140
7.1 Overview 140
7.2 Current Approaches to CDI Product Development 142
7.2.1 Antibiotics 142
7.2.2 Non-Antibiotic Adjunctive Therapeutics 143
7.2.3 Non-Antibiotic Prophylactic Agents 148
7.2.4 Vaccines 149
7.3 Clinical Trial Design 150
7.3.1 Therapeutic Agents 150
7.3.2 Prophylactic Agents 153
7.4 Special Considerations for Future Clinical Development 155
7.4.1 Patient Selection in Late-Stage Efficacy Studies for Prophylactic Products 155
7.4.2 Active Comparators and Superiority Trial Designs for New CDI-Specific Antibiotics 157
7.4.3 Rationally Designed Microbiologics Need to Show Superior Safety Profiles Compared to FMT 158
8 Pipeline Assessment 160
8.1 Overview 160
8.2 Promising Products in Clinical Development 161
8.3 Therapeutic Agents - Biologics and Immunotherapies 164
8.3.1 Actoxumab and Bezlotoxumab (anti-C. difficile toxins A and B) 164
8.4 Therapeutic Agents - Antibiotics 174
8.4.1 Cadazolid 174
8.4.2 Surotomycin 179
8.4.3 SMT19969 185
8.5 Therapeutic Agents - Microbiologics 189
8.5.1 SER-109 (firmacute eubacterial spores, purified suspensions, encapsulated) 189
8.5.2 RBX2660 (microbiota suspension) 196
8.6 Prophylactic Agents - Vaccines 202
8.6.1 ACAM-CDIFF 202
8.6.2 VLA84 208
8.6.3 PF-06425090 214
8.7 Other Innovative Products and Approaches to CDI Prevention and Treatment 220
8.7.1 LFF571 220
8.7.2 Ramoplanin 223
8.7.3 VP20621 (non-toxigenic C. difficile strain M3 spores) 226
8.7.4 SYN-004 231
8.8 Other CDI Products in Development 233
9 Pipeline Valuation Analysis 235
9.1 Clinical Benchmark of Key Pipeline Products 235
9.1.1 Therapeutic Agents 235
9.1.2 Prophylactic Agents 236
9.2 Commercial Benchmark of Key Pipeline Products 237
9.2.1 Therapeutic Agents 237
9.2.2 Prophylactic Agents 239
9.3 Competitive Assessment 240
9.3.1 Therapeutic Agents 240
9.3.2 Prophylactic Agents 242
9.4 Top-Line 10-Year Forecast 244
9.4.1 US 250
9.4.2 5EU 253
9.4.3 Japan 257
10 Appendix 261
10.1 Bibliography 261
10.2 Abbreviations 295
10.3 Methodology 299
10.4 Forecasting Methodology 299
10.4.1 CDI Patient Population Segmentation 299
10.4.2 Percent Product-Treated Patients 300
10.4.3 Products Included in Each Therapeutic Class 302
10.4.4 Pipeline Product Projected Launch Dates 303
10.4.5 General Pricing Assumptions 303
10.4.6 Individual Product Assumptions 304
10.4.7 Pricing of Pipeline Products 311
10.5 Primary Research 315
10.5.1 Physicians and Specialists Included in this Study 315
10.5.2 Online Survey of High-Prescribing Physicians 317
10.6 About the Authors 318
10.6.1 Analyst 318
10.6.2 Epidemiologist 318
10.6.3 Therapy Area Director 319
10.6.4 Global Director of Therapy Analysis and Epidemiology 319
10.6.5 Global Head of Healthcare 320
10.7 About GlobalData 321
10.8 Disclaimer 321
List Of Tables
1.1 List of Tables
Table 1: Antimicrobial Agents that May Induce CDI, CDAD, and Colitis 27
Table 2: Physiological Effects of C. difficile Toxins A and B 31
Table 3: Risk Factors Associated with CDI and CDAD 33
Table 4: Clinical Variants of CDI and Associated Symptoms 34
Table 5: Summary of Stool Laboratory Diagnostic Testing for C. difficile 37
Table 6: CDI Severity Scoring System and Summary of Recommended Treatments 41
Table 7: Risk Factors and Comorbidities for CDI 47
Table 8: Definitions of CDI Segmentations 53
Table 9: 7MM, Sources of CDI Diagnosed Incidence Data 54
Table 10: 7MM, Sources of CDI Recurrence Rates 55
Table 11: 7MM, Sources of CDI Epidemiological Association 56
Table 12: 7MM, Sources Not Used in Epidemiological Analysis of CDI 62
Table 13: 7MM, Diagnosed Incident Cases of All-CDI, Ages ?18 Years, Both Sexes, N, Selected Years 2014-2024 70
Table 14: 7MM, Age-Specific Diagnosed Incident Cases of All-CDI, Ages ?18 Years, Both Sexes, N, 2014. 72
Table 15: 7MM, Sex-Specific Diagnosed Incident Cases of All-CDI, Ages ?18 Years, N, 2014 74
Table 16: Product Profile - Metronidazole 88
Table 17: Adverse Reactions Reported During Treatment with Metronidazole 89
Table 18: Metronidazole SWOT Analysis, 2015 91
Table 19: Product Profile - Vancomycin 94
Table 20: Clinical Success of Vancomycin-Treated Subjects in Two Clinical Trials 95
Table 21: Common Adverse Reactions for Vancomycin in Treating CDAD* 96
Table 22: Vancomycin SWOT Analysis, 2015 97
Table 23: Product Profile - Dificid 100
Table 24: Dificid Pivotal Phase III Clinical Trials Response Rates 102
Table 25: Dificid Pivotal Phase III Clinical Trials Sustained Clinical Response at 25 Days After Treatment According to C. difficile Strain 103
Table 26: Selected Adverse Reactions with an Incidence of ?2% Reported in Patients Treated with Dificid in Controlled Trials 104
Table 27: Dificid SWOT Analysis, 2015 105
Table 28: Unmet Need and Opportunity in Clostridium difficile Infections 119
Table 29: Key Products in the CDI Market by Therapeutic Class, 2015 141
Table 30: Clinical Trial Designs for CDI Pipeline Therapeutic Agents 152
Table 31: Clinical Trial Designs for CDI Pipeline Prophylactic Agents 155
Table 32: Promising Products in Clinical Development for CDIs, 2015 163
Table 33: Product Profile - Actoxumab and Bezlotoxumab 167
Table 34: Efficacy of Actoxumab and Bezlotoxumab in Terms of CDI Recurrence, Phase II Trial 170
Table 35: Most Common AEs and SAEs Documented After Treatment with Actoxumab and Bezlotoxumab, Phase II Triala 172
Table 36: Actoxumab and Bezlotoxumab SWOT Analysis, 2015 173
Table 37: Product Profile - Cadazolid 176
Table 38: Efficacy Results from Cadazolid Phase II Trial - Modified Intent-to-Treat Populationa 177
Table 39: Cadazolid SWOT Analysis, 2015 179
Table 40: Product Profile - Surotomycin 181
Table 41: Efficacy Results from Surotomycin Phase II Trial - Modified Intent-to-Treat Populationa 183
Table 42: Surotomycin SWOT Analysis, 2015 184
Table 43: Product Profile - SMT19969 187
Table 44: SMT19969 SWOT Analysis, 2015 189
Table 45: Product Profile - SER-109 192
Table 46: SER-109 SWOT Analysis, 2015 195
Table 47: Product Profile - RBX2660 198
Table 48: RBX2660 SWOT Analysis, 2015 201
Table 49: Product Profile - ACAM-CDIFF 204
Table 50: Formulations and Dosing Schedules for ACAM-CDIFF Phase II Trial 205
Table 51: ACAM-CDIFF SWOT Analysis, 2015 208
Table 52: Product Profile - VLA84 211
Table 53: Doses and Dosing Schedules in VLA84 Phase I Trial* 212
Table 54: VLA84 SWOT Analysis, 2015 214
Table 55: Product Profile - PF-06425090 217
Table 56: PF-06425090 SWOT Analysis, 2015 219
Table 57: Innovative Early-Stage Approaches to CDI Prevention and Treatment, 2015 220
Table 58: Phase II Clinical Trial Efficacy Data for LFF571 222
Table 59: Phase II Clinical Trial Safety Data for LFF571 223
Table 60: Efficacy Data from Phase II Clinical Trial of VP20621 228
Table 61: Safety Data from Phase II Clinical Trial of VP20621 229
Table 62: Other CDI Products in Development, 2015 233
Table 63: Clinical Benchmarking of Key CDI Therapeutic Agents, 2015 236
Table 64: Clinical Benchmarking of Key CDI Pipeline Prophylactic Agents, 2015 237
Table 65: Commercial Benchmarking of Key CDI Therapeutic Agents, 2015 238
Table 66: Commercial Benchmarking of Key CDI Pipeline Prophylactic Agents, 2015 240
Table 67: Top-Line Global Sales Forecasts for CDI Therapeutic and Prophylactic Agents, 2014-2024* 246
Table 68: Key Events Impacting Sales from CDI Therapeutics and Prophylactics, 2014-2024 248
Table 69: Global CDI Products Market - Drivers and Barriers, 2014-2024 249
Table 70: CDI Patient Population Segmentations in the 7MM - Secondary Sources Leveraged 300
Table 71: Patient Populations Targeted by CDI Marketed and Pipeline Product Developers 301
Table 72: CDI Marketed and Pipeline Products Broken Down by Therapeutic Class 302
Table 73: Key Pipeline Product Projected Launch Dates by Region 303
Table 74: High-Prescribing Physicians (Non-KOLs) Surveyed, By Country 317
List Of Figures
1.2 List of Figures
Figure 1: Examples of C. difficile-Associated Diseases 26
Figure 2: Overview of the Pathogenesis of CDAD 30
Figure 3: Top-Level Overview of International Treatment Algorithm for CDI and CDAD 39
Figure 4: Incidence Rate for CDI in the 7MM, 2014 49
Figure 5: Case Flow Map for the US 57
Figure 6: Case Flow Map for the 5EU and Japan 58
Figure 7: 7MM, Diagnosed Incident Cases of All-CDI, Ages ?18 Years, Both Sexes, N, 2014-2024 71
Figure 8: Age-Specific Diagnosed Incident Cases of All-CDI, Ages ?18 Years, Both Sexes, N, 2014 73
Figure 9: 7MM, Sex-Specific Diagnosed Incident Cases of All-CDI, Ages ?18 Years, N, 2014 75
Figure 10: 7MM, Age-Standardized Diagnosed Incidence Rates of All-CDI, 2014 76
Figure 11: 5EU and Japan, Recurrent CDI Cases, Ages ?18 Years, N, 2014 77
Figure 12: US, Diagnosed Incident Cases of CDI Stratified by Recurrence, Ages ?18 Years, N, 2014 78
Figure 13: 5EU and Japan, Diagnosed Incident Cases of All-CDI Stratified by Epidemiological Association, Ages ?18 Years, N, 2014 79
Figure 14: US, Diagnosed Incident Cases of All-CDI by Epidemiological Association, Ages ?18 Years, N, 2014 80
Figure 15: Current Treatment Options for CDIs 85
Figure 16: Competitive Assessment of Key CDI Therapeutic Agents, 2015 242
Figure 17: Competitive Assessment of Key CDI Pipeline Prophylactic Agents, 2015 244
Figure 18: Global Sales from CDI Therapeutic and Prophylactic Agents by Region, 2014 and 2024* 247
Figure 19: US Sales from CDI Therapeutic Agents, 2014 and 2024* 251
Figure 20: US Sales from CDI Prophylactic Agents, 2014-2024 253
Figure 21: 5EU Sales from CDI Therapeutic Agents, 2014 and 2024* 255
Figure 22: 5EU Sales from CDI Prophylactic Agents, 2014-2024 257
Figure 23: Japan Sales from CDI Therapeutic Agents, 2014 and 2024* 258
Figure 24: Japan Sales from CDI Prophylactic Agents, 2014-2024 260
