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CHAPTER 1 EXECUTIVE SUMMARY 3 Scope of analysis 3 Our insight into the colorectal cancer market 4 The recent introduction of Avastin and Erbitux into the colorectal cancer market will raise the standard for approval, making it more difficult for pipeline drugs to gain approval. However, at the same time, it will increase opportunities for these pipeline drugs to maximize their commercial potential by combining with Avastin and Erbitux 5 The approval of Avastin will increase confidence in angiogenesis inhibitors as a whole. Despite this, there is a lack of angiogenesis inhibitors in late-stage development and the only competitive threat to Avastin is likely to come from Novartis’s PTK787 in the short to medium term. Nevertheless, We believe that PTK787 will significantly threaten the potential dominance of Avastin in the colorectal cancer market 6 There is significant pharmaceutical and biotechnology interest in vaccines, reflected by the high number of agents in development in Phase II and III for colorectal cancer. However, cancer vaccines are generally burdened by physicians’ skepticism and, as a result, they may struggle to establish a presence in the colorectal cancer market 8 Signal transduction inhibitors are one of the earliest innovative agents to be launched for the treatment of cancer. For colorectal cancer, the class is represented by BMS/Merck KGaA/ImClone’s Erbitux. Amgen/Abgenix’s ABX-EGF is likely to be the main competition for Erbitux, however, its third-line indication will be its weak point and Datamonitor forecasts a low sales potential for the drug 10 Given the established presence of existing cytotoxic agents and the emergence of targeted agents in the coming years for colorectal cancer, many cytotoxic agents currently in development may struggle to gain a foothold in the colorectal cancer market. However, Lilly’s Alimta has the potential to replace 5-FU as the core drug for colorectal cancer treatment 11 Key metrics 13 Summary of research/clinical and commercial attractiveness of launched and Phase III drugs for colorectal cancer 15 CHAPTER 2 COLORECTAL CANCER OVERVIEW 22 The colon and rectum 22 Causes of colorectal cancer 23 Risk factors of colorectal cancer 23 Screening 25 Need to increase profile and awareness of colorectal cancer 27 Diagnosis 27 Effectiveness of diagnostic tests as screening tools 29 Histology 30 Staging 31 Patient distribution by stage 32 Epidemiology 32 CHAPTER 3 CURRENT TREATMENT OVERVIEW 36 Treatment options 36 Surgery options 36 Radiotherapy 37 Chemotherapy 38 Recently approved innovative therapies 38 CHAPTER 4 R&D APPROACH 39 Classification of pipeline drugs 39 Cytotoxics 39 Comparison 43 Signal transduction inhibitors 43 Angiogenesis inhibitors 44 Apoptosis stimulators 44 Immunostimulators 44 Clinical trial designs in colorectal cancer 45 New treatment paradigms 45 Clinical trial duration 46 Patient selection 46 Comparator drugs 47 Clinical trial endpoints in colorectal cancer 48 Survival 48 Response rates 48 Toxicity 48 Quality of life 49 Time-to-tumor progression 49 CHAPTER 5 PIPELINE DRUG CLASS ANALYSIS 50 Pipeline overview 50 High attrition rate reflected in lack of Phase III drugs 50 Pipeline analysis by classification 52 Pipeline drugs for colorectal cancer by phase 55 Currently players in the colorectal cancer market 58 CHAPTER 6 PIPELINE DRUG ANALYSIS 62 Comparator drugs 62 Erbitux (cetuximab) 62 Avastin (bevacizumab) 72 Eloxatin (oxaliplatin) 82 Summary table of efficacy of comparator drugs 87 Phase III drugs 88 ABX-EGF (panitumumab) 88 PTK787 (vatalanib) 97 IGN101 109 OncoVAX 114 Summary of research/clinical and commercial attractiveness of launched and Phase III drugs for colorectal cancer 123 Phase II drugs 125 Cytotoxics 126 Vaccines 143 Angiogenesis inhibitors 159 Signal transduction inhibitors 165 Apoptosis stimulators 174 Others 174 Summary of research/clinical and commercial attractiveness of key Phase II drugs for colorectal cancer 179 Key completed and ongoing clinical trials in Phase III 181 CHAPTER 7 APPENDIX 182 Pipeline drug assessment methodology 182 Forecast methodology 185 References 186 Research and analysis methodologies 203