Colorectal cancer (CRC) is the second leading cause of mortality among cancer patients in the world and is the third most diagnosed cancer globally, and thus represents a huge burden on healthcare systems. This report focuses on the current treatment landscape, unmet needs, current pipeline, and commercial opportunities in the colorectal cancer market, with coverage of multiple settings of the disease including neoadjuvant/adjuvant, first-, second-, third-line KRAS wild-type and mutation-positive, and fourth-line metastatic. In terms of targeted treatments, the metastatic CRC treatment landscape is mature, including the branded treatments Avastin (bevacizumab), Erbitux (cetuximab), and Vectibix (panitumumab), treatments that have extended the survival of metastatic patients compared to chemotherapy-only regimens. However, high unmet needs remain for the extension of survival of metastatic patients, and particularly those with KRAS mutation-positive disease, for whom the epidermal growth factor receptor (EGFR) inhibitors Erbitux and Vectibix are not recommended. The CRC market is expected to grow due to the incorporation of five late-stage pipeline agents during the forecast period, including Mologen’s MGN1703, Eli Lilly’s Cyramza, and Boehringer Ingelheim’s nintedanib. Furthermore, GlobalData expects the label extension of Stivarga as a first-line adjuvant treatment for metastatic CRC patients with resected liver metastases. Ultimately, however, GlobalData expects unmet needs to remain unfulfilled by these pipeline agents, and anticipates that novel, innovative approaches, such as those targeting BRAF mutation-positive disease and immune checkpoint inhibitors, will provide the best opportunity for substantial improvement in the prognosis of advanced CRC patients.

Highlights

Key Questions Answered

• What are the corporate strategies being used by drug makers?
• How is the disease management evolving? What is the impact for drug manufacturers?
• What opportunities remain after the launch of pipeline agents?
• How large are the metastatic KRAS wild-type and mutation-positive CRC markets for branded agents, and which are growing the fastest?
• What exciting, innovative approaches are being investigated in CRC? Which immunotherapies are of interest to the CRC market?
• What do KOLs think about the latest therapies and drug development strategies?

Key Findings

• By 2023, the end of the forecast period, GlobalData projects CRC sales to rise to $8.11 billion in the 8MM, at a moderate Compound Annual Growth Rate (CAGR) of 4.9%. Major drivers of the growth of the CRC market over the forecast period include increasing CRC incident cases, the launch of premium-priced adjuvant and maintenance treatments for first-line metastatic disease, and the launch of pipeline agents for later-line CRC.
• Roche’s anti-angiogenesis drug Avastin has been the best-selling brand in CRC for many years, and, after label extension in the second-line continuation setting, is set to remain the market leader across the forecast period. However, competition in this drug class is expected to become more intense, especially in the second-line metastatic setting, as Sanofi/Regeneron’s Zaltrap and Eli Lilly’s pipeline agent Cyramza (ramucirumab) garner uptake across the major markets.
• GlobalData expects the next surge of anti-angiogenesis drugs to be focused on the anti-Ang2 inhibitor class. This class is likely to be led by Roche’s dual anti-VEGF/Ang2 inhibiting antibody vanucizumab (RO5520985; RG7221). Roche is currently investigating vanucizumab head-to-head against Avastin in a randomized Phase II study. If this agent is successful in a large, pivotal study, GlobalData anticipates vanucizumab to become a key part of Roche’s strategy to overcome biosimilar erosion of Avastin towards the end of the forecast period.
• Interviewed KOLs are enthusiastic about early-stage innovative approaches targeting metastatic CRC patients with BRAF and KRAS mutation-positive disease, and immune checkpoint inhibitors such as the anti-PD1/PDL1 drugs. With Big Pharma taking a leading role, GlobalData expects the targeted, biomarker-driven approach for the treatment of metastatic CRC to become a significant R&D strategy for developers during and beyond the forecast period.

Scope

• Overview of colorectal cancer, including epidemiology, etiology, pathophysiology, symptoms, diagnosis, and disease management.
• Annualized Colorectal cancer therapeutics market revenue, annual cost of therapy, and treatment usage patterns in eight patient segments, forecast from 2013 to 2023.
• Key topics covered include strategic competitor assessment, market characterization, unmet needs, remaining commercial opportunities, and current and future players for the colorectal cancer therapeutics market.
• Pipeline analysis: comprehensive data assessing emerging trends and mechanisms of action under development for different lines of therapy. The most promising candidates in Phase III development are profiled.
• Analysis of the current and future market competition in the global colorectal cancer therapeutics 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

• 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 colorectal cancer therapeutics market.
• Drive revenues by understanding the key trends, innovative products and technologies, market segments, and companies likely to impact the global colorectal cancer therapeutics market in the future.
• Formulate effective sales and marketing strategies by understanding the competitive landscape and by analysing 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 10
1.1 List of Tables 16
1.2 List of Figures 21

2 Introduction 23
2.1 Catalyst 23
2.2 Related Reports 24
2.3 Upcoming Related Reports 24

3 Disease Overview 25
3.1 Etiology and Pathophysiology 25
3.1.1 Etiology 25
3.1.2 Pathophysiology 27
3.2 Clinical Staging 28
3.3 Symptoms 29

4 Epidemiology 31
4.1 Disease Background 31
4.2 Risk Factors and Comorbidities 31
4.3 Global Trends 34
4.3.1 8MM, Incidence Trends 34
4.3.2 8MM, Five-Year Relative Survival 36
4.3.3 8MM, Screening Programs for CRC 37
4.4 Forecast Methodology 39
4.4.1 Sources Used 40
4.4.2 Sources Not Used 47
4.4.3 Forecast Assumptions and Methods 48
4.5 Epidemiological Forecast of CRC (2013-2023) 52
4.5.1 Diagnosed Incident Cases of CRC 52
4.5.2 Age-Specific Diagnosed Incident Cases of CRC 54
4.5.3 Sex-Specific Diagnosed Incident Cases of CRC 55
4.5.4 Age-Standardized Incidence 57
4.5.5 Cancer Stage at Diagnosis 58
4.5.6 Diagnosed Five-Year Prevalent Cases of CRC 59
4.5.7 KRAS Status among Diagnosed Five-Year Prevalent Cases of CRC 61
4.6 Discussion 61
4.6.1 Epidemiological Forecast Insight 61
4.6.2 Limitations of the Analysis 63
4.6.3 Strengths of the Analysis 64

5 Disease Management 65
5.1 Diagnosis and Treatment Overview 65
5.1.1 Screening and Diagnosis 65
5.1.2 Treatment Guidelines and Leading Prescribed Drugs 68
5.1.3 Clinical Practice 72
5.2 US 78
5.2.1 Screening and Diagnosis 80
5.2.2 Clinical Practice 81
5.3 France 83
5.3.1 Screening and Diagnosis 85
5.3.2 Clinical Practice 85
5.4 Germany 87
5.4.1 Screening and Diagnosis 89
5.4.2 Clinical Practice 89
5.5 Italy 91
5.5.1 Screening and Diagnosis 93
5.5.2 Clinical Practice 93
5.6 Spain 95
5.6.1 Screening and Diagnosis 97
5.6.2 Clinical Practice 97
5.7 UK 99
5.7.1 Screening and Diagnosis 101
5.7.2 Clinical Practice 101
5.8 Japan 103
5.8.1 Screening and Diagnosis 105
5.8.2 Clinical Practice 105
5.9 China 107
5.9.1 Screening and Diagnosis 108
5.9.2 Clinical Practice 108

6 Competitive Assessment 110
6.1 Overview 110
6.2 Product Profiles — Major Brands 111
6.2.1 Avastin (Bevacizumab) 111
6.2.2 Erbitux (Cetuximab) 117
6.2.3 Vectibix (Panitumumab) 122
6.2.4 Stivarga (Regorafenib) 126
6.2.5 Zaltrap (Ziv-Aflibrcept) 131
6.2.6 Lonsurf (TAS-102) 135
6.2.7 TS-1 (Tegafur, Gimeracil, Oteracil) 140
6.2.8 Xeloda (Capecitabine) 144

7 Unmet Need and Opportunity 148
7.1 Overview 148
7.2 Therapies That Provide Substantial Overall Survival Benefit for Metastatic Patients 149
7.2.1 Unmet Need 149
7.2.2 Gap Analysis 151
7.2.3 Opportunity 151
7.3 Targeted Treatments for KRAS and BRAF Mutaton-Positive Patients 153
7.3.1 Unmet Need 153
7.3.2 Gap Analysis 154
7.3.3 Opportunity 154
7.4 Effective Neoadjuvant/Adjuvant Therapies for High Risk Resectable Disease 155
7.4.1 Unmet Need 155
7.4.2 Gap Analysis 156
7.4.3 Opportunity 156
7.5 Tolerable Later-Line Therapies For Chemotherapy-Resistant Patients 157
7.5.1 Unmet Need 157
7.5.2 Gap Analysis 157
7.5.3 Opportunity 158

8 Pipeline Assessment 159
8.1 Overview 159
8.2 Promising Drugs in Clinical Development 160
8.2.1 Cyramza (Ramucirumab) 161
8.2.2 Imprime PGG 167
8.2.3 MGN1703 173
8.2.4 Nintedanib (BIBF-1120) 179
8.3 Promising Approaches in Early-Stage Development 184
8.3.1 Anti-Angiopoietin-2 Inhibitors 184
8.3.2 Strategies for BRAF Mutation-Positive Disease 186
8.3.3 Strategies for KRAS-Mutation Positive Disease 192
8.3.4 Immune Checkpoint Inhibitors 196

9 Current and Future Players 201
9.1 Overview 201
9.2 Trends in Corporate Strategy 205
9.3 Company Profiles 207
9.3.1 Roche/Genentech 207
9.3.2 Sanofi 211
9.3.3 Eli Lilly and Company 214
9.3.4 Merck KGaA 217
9.3.5 Bayer 220
9.3.6 Taiho Pharmaceutical 223

10 Market Outlook 226
10.1 Global Markets 226
10.1.1 Forecast 226
10.1.2 Drivers and Barriers - Global Issues 230
10.2 United States 233
10.2.1 Forecast 233
10.2.2 Key Events 237
10.2.3 Drivers and Barriers 237
10.3 France 240
10.3.1 Forecast 240
10.3.2 Key Events 244
10.3.3 Drivers and Barriers 244
10.4 Germany 247
10.4.1 Forecast 247
10.4.2 Key Events 251
10.4.3 Drivers and Barriers 251
10.5 Italy 253
10.5.1 Forecast 253
10.5.2 Key Events 257
10.5.3 Drivers and Barriers 257
10.6 Spain 259
10.6.1 Forecast 259
10.6.2 Key Events 263
10.6.3 Drivers and Barriers 263
10.7 United Kingdom 265
10.7.1 Forecast 265
10.7.2 Key Events 269
10.7.3 Drivers and Barriers 269
10.8 Japan 272
10.8.1 Forecast 272
10.8.2 Key Events 276
10.8.3 Drivers and Barriers 276
10.9 China 278
10.9.1 Forecast 278
10.9.2 Key Events 282
10.9.3 Drivers and Barriers 282

11 Appendix 286
11.1 Bibliography 286
11.2 Abbreviations 322
11.3 Methodology 329
11.4 Forecasting Methodology 329
11.4.1 Diagnosed Colorectal Cancer Patients 329
11.4.2 Percent Drug-Treated Patients 330
11.4.3 Drugs Included in Each Therapeutic Class 330
11.4.4 Launch and Patent Expiration Dates 331
11.4.5 General Pricing Assumptions 332
11.4.6 Average Body Weight and Surface Area Across the 8MM 333
11.4.7 Individual Drug Assumptions 333
11.4.8 Generic Erosion 339
11.4.9 Pricing of Pipeline Agents 339
11.5 Primary Research - KOLs Interviewed for this Report 340
11.6 Primary Research - Prescriber Survey 342
11.7 About the Authors 343
11.7.1 Analyst 343
11.7.2 Epidemiologist 343
11.7.3 Global Head of Healthcare 344
11.8 About GlobalData 345
11.9 Disclaimer 345

List of Tables

Table 1: TNM and Staging Classification System for CRC 29
Table 2: Symptoms of Colorectal Cancer 30
Table 3: Risk Factors and Comorbidities for CRC 33
Table 4: 8MM, Five-Year Relative Survival 37
Table 5: 8MM, Sources of CRC Incidence Data 40
Table 6: 8MM, Sources of CRC Diagnosed Five-Year Prevalent Cases Data 42
Table 7: 8MM, Sources of CRC Cancer Stage at Diagnosis Data 43
Table 8: 8MM, Diagnosed Incident Cases of CRC, Both Sexes, Ages ?20 Years, N, 2013-2023 53
Table 9: 8MM, Age-Specific Diagnosed Incident Cases of CRC, Both Sexes, N, Row (%), 2013 54
Table 10: 8MM, Sex-Specific Diagnosed Incident Cases of CRC, Ages ?20 Years, 2013 56
Table 11: 8MM, Diagnosed Five-Year Prevalent Cases of CRC, Both Sexes, Ages ?20 Years, N, 2013-2023 60
Table 12: 8MM, KRAS Status among CRC Prevalent Cases, 2013 61
Table 13: Treatment Guidelines for CRC 69
Table 14: Most-Prescribed Neoadjuvant/Adjuvant Regimens for Early-Stage CRC in the Global Markets, 2013 70
Table 15: Most Prescribed Targeted Therapies for Metastatic CRC by Segment in the Global Markets, 2013 71
Table 16: Country Profile - US 79
Table 17: Country Profile - France 84
Table 18: Country Profile - Germany 88
Table 19: Country Profile - Italy 92
Table 20: Country Profile - Spain 96
Table 21: Country Profile - UK 100
Table 22: Country Profile - Japan 104
Table 23: Country Profile - China 107
Table 24: Leading Treatments for CRC, 2014 111
Table 25: Product Profile — Avastin 113
Table 26: Avastin SWOT Analysis, 2014 115
Table 27: Global Sales Forecast ($m) for Avastin, 2013-2023 116
Table 28: Product Profile — Erbitux 118
Table 29: Erbitux SWOT Analysis, 2014 120
Table 30: Global Sales Forecast ($m) for Erbitux, 2013-2023 121
Table 31: Product Profile - Vectibix 123
Table 32: Vectibix SWOT Analysis, 2014 125
Table 33: Global Sales Forecast ($m) for Vectibix, 2013-2023 126
Table 34: Product Profile - Stivarga 128
Table 35: Stivarga SWOT Analysis, 2014 130
Table 36: Global Sales Forecasts ($m) for Stivarga, 2013-2023 131
Table 37: Product Profile - Zaltrap 133
Table 38: Zaltrap SWOT Analysis, 2014 134
Table 39: Global Sales Forecasts ($m) for Zaltrap, 2013-2023 135
Table 40: Product Profile - Lonsurf 137
Table 41: Lonsurf SWOT Analysis, 2014 139
Table 42: Global Sales Forecasts ($m) for Lonsurf (TAS-102), 2013-2023 140
Table 43: Product Profile - TS-1 141
Table 44: TS-1 SWOT Analysis, 2014 143
Table 45: Global Sales Forecasts ($m) for TS-1, 2013-2023 144
Table 46: Product Profile - Xeloda 145
Table 47: Unmet Need and Opportunity in CRC 149
Table 48: Product Profile - Cyramza 164
Table 49: Cyramza SWOT Analysis, 2014 166
Table 50: Global Sales Forecasts ($m) for Cyramza, 2013-2023 167
Table 51: Product Profile - Imprime PGG 169
Table 52: Imprime PGG SWOT Analysis, 2014 172
Table 53: Global Sales Forecasts ($m) for Imprime PGG, 2013-2023 173
Table 54: Product Profile - MGN1703 175
Table 55: MGN1703 SWOT Analysis, 2014 178
Table 56: Global Sales Forecasts ($m) for MGN1703, 2013-2023 179
Table 57: Product Profile - Nintedanib 180
Table 58: Nintedanib SWOT Analysis, 2014 183
Table 59: Global Sales Forecasts ($m) for Nintedanib, 2013-2023 183
Table 60: Anti-Angiopoietin-2 Inhibitors in Development 184
Table 61: Early-stage Strategies for BRAF Mutation-Positive CRC 187
Table 62: Early-stage Strategies for KRAS Mutation-Positive CRC 193
Table 63: Anti-PD1 and Anti-PDL1 Drugs in Early-Stage Development for CRC 197
Table 64: Key Companies in the CRC Market in the 8MM, 2013-2023 203
Table 65: Roche's CRC Portfolio Assessment, 2014 209
Table 66: Sanofi's CRC Portfolio Assessment, 2014 212
Table 67: Eli Lilly's CRC Portfolio Assessment, 2014 215
Table 68: Merck KGaA's CRC Portfolio Assessment, 2014 218
Table 69: Bayer's CRC Portfolio Assessment, 2014 221
Table 70: Taiho's CRC Portfolio Assessment, 2014 224
Table 71: Sales Forecasts ($m) for Colorectal Cancer in the Global Markets, 2013-2023 228
Table 72: CRC Market Drivers and Barriers, 2014 230
Table 73: Sales Forecasts ($m) for Colorectal Cancer in the United States, 2013-2023 235
Table 74: Key Events Impacting Sales for CRC in the US, 2014 237
Table 75: US CRC Market Drivers and Barriers, 2014 237
Table 76: Sales Forecasts ($m) for Colorectal Cancer in France, 2013-2023 242
Table 77: Key Events Impacting Sales for CRC in France, 2014 244
Table 78: France CRC Market Drivers and Barriers, 2014 244
Table 79: Sales Forecasts ($m) for Colorectal Cancer in Germany, 2013-2023 249
Table 80: Key Events Impacting Sales for CRC in Germany, 2014 251
Table 81: Germany CRC Market Drivers and Barriers, 2014 251
Table 82: Sales Forecasts ($m) for Colorectal Cancer in Italy, 2013-2023 255
Table 83: Key Events Impacting Sales for CRC in Italy, 2014 257
Table 84: Italy CRC Market Drivers and Barriers, 2014 257
Table 85: Sales Forecasts ($m) for Colorectal Cancer in Spain, 2013-2023 261
Table 86: Key Events Impacting Sales for CRC in Spain, 2014 263
Table 87: Spain CRC Market Drivers and Barriers, 2014 263
Table 88: Sales Forecasts ($m) for Colorectal Cancer in the UK, 2013-2023 267
Table 89: Key Events Impacting Sales for CRC in the UK, 2014 269
Table 90: UK CRC Market - Drivers and Barriers, 2014 269
Table 91: Sales Forecasts ($m) for Colorectal Cancer in Japan, 2013-2023 274
Table 92: Key Events Impacting Sales for CRC in Japan, 2014 276
Table 93: Japan CRC Market - Drivers and Barriers, 2014 276
Table 94: Sales Forecasts ($m) for Colorectal Cancer in China, 2013-2023 280
Table 95: Key Events Impacting Sales for CRC in China, 2014 282
Table 96: China CRC Market - Drivers and Barriers, 2014 282
Table 97: Key Launch Dates 331
Table 98: Key Patent Expiries 331
Table 99: Average Body Weight and Surface Area Across the 8MM 333
Table 100: High-Prescribing Physicians (non-KOLs) Surveyed, By Country 342

List of Figures

Figure 1: Historical Age-Adjusted CRC Incidence (Cases per 100,000 Population) in 8MM, Men, 1998-2007 35
Figure 2: Historical Age-Adjusted CRC Incidence (Cases per 100,000 Population), in 8MM, Women, 1998-2007 36
Figure 3: 8MM, Diagnosed Incident Cases of CRC, Both Sexes, Ages ?20 Years, N, 2013-2023 53
Figure 4: 8MM, Age-Specific Diagnosed Incident Cases of CRC, Both Sexes, N, 2013 55
Figure 5: 8MM, Sex-Specific Diagnosed Incident Cases of CRC, Ages ?20 Years, 2013 57
Figure 6: 8MM, Age-Standardized Incidence of CRC (Cases per 100,000 Population), Ages ?20 Years, by Sex, 2013. 58
Figure 7: 8MM, Cancer Stage at Diagnosis Percentage Distribution, Ages ?20 Years. 59
Figure 8: 8MM, Diagnosed Five-Year Prevalent Cases of CRC, Both Sexes, Ages ?20 Years, N, 2013-2023 60
Figure 9: CRC - Phase III Pipeline 160
Figure 10: Competitive Assessment of Late-Stage Pipeline Agents in CRC, 2013-2023 161
Figure 11: Clinical and Commercial Positioning of Cyramza 165
Figure 12: Clinical and Commercial Positioning of Imprime PGG 171
Figure 13: Clinical and Commercial Positioning of MGN1703 177
Figure 14: Clinical and Commercial Positioning of Nintedanib 182
Figure 15: Global Sales of Branded Products for Colorectal Cancer by Company, 2013-2023 204
Figure 16: Company Portfolio Gap Analysis in CRC, 2013-2023 205
Figure 17: Roche SWOT Analysis in CRC, 2014 210
Figure 18: Sanofi SWOT Analysis in CRC, 2014 213
Figure 19: Eli Lilly SWOT Analysis in CRC, 2014 216
Figure 20: Merck KGaA SWOT Analysis in CRC, 2014 219
Figure 21: Bayer SWOT Analysis in CRC, 2014 222
Figure 22: Taiho SWOT Analysis in CRC, 2014 225
Figure 23: Global Sales for Colorectal Cancer by Region, 2013-2023 229
Figure 24: Sales for Colorectal Cancer in the United States by Drug Class, 2013-2023 236
Figure 25: Sales for Colorectal Cancer in France by Drug Class, 2013-2023 243
Figure 26: Sales for Colorectal Cancer in Germany by Drug Class, 2013-2023 250
Figure 27: Sales for Colorectal Cancer in Italy by Drug Class, 2013-2023 256
Figure 28: Sales for Colorectal Cancer in Spain by Drug Class, 2013-2023 262
Figure 29: Sales for Colorectal Cancer in the United Kingdom by Drug Class, 2013-2023 268
Figure 30: Sales for Colorectal Cancer in Japan by Drug Class, 2013-2023 275
Figure 31: Sales for Colorectal Cancer in China by Drug Class, 2013-2023 281