Pipeline Insight: Colorectal Cancer - Growing trend towards personalized medicine

Pipeline Insight: Colorectal Cancer - Growing trend towards personalized medicine

Introduction

CRC incidence will be over 490,000 cases by 2018 in the seven major markets. This large patient base will translate into a high commercial potential for the development of novel, more effective therapies. Currently, there are 77 agents in development for CRC, 4 of which are in late-phase development. Collectively, they are forecast to achieve sales of $1,398m by 2018.

Scope

*Examination of the CRC pipeline with in-depth clinical and commercial profiles of Phase III candidates

*Seven major pharmaceutical market sales forecasts for Phase III pipeline products through to 2018

*Segmentation and analysis of the current CRC pipeline by developmental phase, drug class and company

*Insight and analysis of market potential including commercial opportunity, epidemiology and discussion of unmet needs

Highlights

The CRC pipeline consists of 77 drugs, of which 60% are molecular targeted therapies (MTTs), 22% are immunotherapies, and 17% are cytotoxic therapies. MTTs constitute the bulk of the CRC pipeline. This is in line with R&D in other tumor types, where there is a shift away from standard cytotoxic therapies towards MTTs and personalized medicine.

The late-phase CRC pipeline consists only of MTTs. Except for one agent; all the others are being investigated in previously-treated patients. Drug developers appear to be pursuing approval for treatment in the second-line setting where barriers to market entry are lower and the high level of unmet need may facilitate a drug's uptake and approval.

Aflibercept (VEGF-Trap; Regeneron/Sanofi-Aventis) is forecast to achieve the highest level of sales among the late-phase pipeline candidates in the CRC market, generating £604m by 2018 in the seven major pharmaceutical markets.

Reasons to Purchase

*Identify key drugs and companies within the CRC pipeline based on sales forecasts to 2018 and The author drug assessment.

*Characterize unmet need and poorly served patient subsets within the CRC market and assess the potential for pipeline products to fulfil them.

*Segmentation and analysis of the current CRC pipeline by developmental phase, drug class, company and indication.

Overview 1
Catalyst 1
Summary 1
ABOUT DATAMONITOR HEALTHCARE 2
About the Oncology pharmaceutical analysis team 2
Executive Summary 3
Strategic scoping and focus 3
Datamonitor insight into the colorectal cancer market 3
Datamonitor pipeline assessment summary 4
Related reports 5
Upcoming related reports 6
TABLE OF CONTENTS 7
1. Pipeline Overview and dynamics 8
Key findings 8
Pipeline overview 8
Pipeline summary 8
Novel molecular targeted therapies dominate the current late-phase colorectal cancer pipeline 8
Comparative forecasts 10
Datamonitor pipeline assessment summary 11
Key companies involved in the colorectal cancer (CRC) pipeline 12
Amgen 12
AstraZeneca 13
Roche 15
Key R&D company strategies 17
Ongoing shift towards molecular targeted therapies in colorectal cancer 17
Line extensions of already marketed drugs 18
2. Colorectal cancer - Market Potential 19
Key findings 19
Definition 19
Introduction 19
Colorectal cancer is one of the 'big four' tumors and numbers are set to rise over the next decade 19
Histology 20
Risk factors 20
CRC is predominantly a disease of the elderly 20
People with CRC in the family have a high risk of developing the disease 20
Western style diets contribute to CRC incidence 20
Rise of CRC in the migrant population 21
Symptoms 21
Screening and diagnosis 21
Fecal occult blood test is the most commonly used screening method 21
Endoscopic methods are not ideal for CRC screening 21
CRC screening remains fragmented between countries 22
Patient segmentation 22
Proper staging is essential to the design of treatment plans 22
Epidemiology 22
Seven major markets 22
CRC cases are expected to rise in line with the aging world population 22
Low detection in the early stages of the disease results in a high mortality rate 23
Rest of the world 24
Current treatment options 25
Surgery remains the primary treatment choice for early-stage CRC 25
Adjuvant therapy extends disease-free survival in Stage III patients 26
Combination chemotherapy is the standard of care in metastatic disease 27
Avastin is used predominantly in the US in the first-line setting 28
Erbitux is indicated for use in patients with wild-type KRAS status 28
Vectibix has limited uptake in the treatment of the disease 29
Current comparator therapy 29
Eloxatin (oxaliplatin; Sanofi-aventis) 29
Unmet need in colorectal cancer (CRC) 31
Better screening approaches needed to decrease mortality rates 31
There is a need for more effective therapies in both early-stage and advanced disease 31
Biomarkers and the selection of patients may help improve outcomes 31
Target product profile versus current level of attainment 31
3. R&D Approach 34
Key findings 34
Clinical trial design in colorectal cancer (CRC) 34
Patient selection 34
Clinical trial endpoints in oncology 35
Overall survival 35
Disease-free survival 36
Overall response rates 36
Progression-free survival 36
Disease control 37
Toxicity 37
4. Pipeline Analysis & Forecasts: Molecular Targeted Therapies 38
Key findings 38
Overview of the molecular targeted therapies 38
Pipeline summary 39
Comparative forecasts 40
Aflibercept (VEGF-Trap; Regeneron/Sanofi-aventis) 42
Drug overview 42
Drug profile 43
Key historical events 43
SWOT analysis 44
Clinical trial data 45
Phase II studies show aflibercept to be well tolerated in metastatic CRC 46
Clinical attractiveness 47
Commercial attractiveness 47
Datamonitor drug assessment summary 49
Satisfaction of unmet needs 49
Forecasts to 2018 50
Brivanib (Bristol-Myers Squibb) 51
Drug overview 51
Drug profile 51
Key historical events 52
SWOT analysis 52
Clinical trial data 53
The combination of brivanib with Erbitux is tolerable and shows signs of clinical activity 54
Retrospective study shows that efficacy of brivanib with Erbitux is driven by wild-type KRAS patients 54
Clinical attractiveness 55
Commercial attractiveness 57
Datamonitor drug assessment summary 58
Satisfaction of unmet needs 58
Forecasts to 2018 59
Recentin (cediranib; AstraZeneca) 60
Drug overview 60
Drug profile 60
Key historical events 61
SWOT analysis 61
Clinical trial data 62
Recentin shows disappointing results in a Phase II head-to-head trial against Avastin 63
Clinical attractiveness 64
Commercial attractiveness 65
Datamonitor drug assessment summary 66
Satisfaction of unmet needs 66
Forecasts to 2018 67
MK-0646 (Merck/Pierre Fabre) 68
Drug overview 68
Drug profile 68
Key historical events 69
SWOT analysis 69
Clinical trial data 70
Phase II shows MK-0646 to be tolerable in metastatic patients with wild-type KRAS 71
Clinical attractiveness 72
Commercial attractiveness 72
Datamonitor drug assessment summary 73
Satisfaction of unmet needs 74
Forecasts to 2018 75
5. Innovative Early-Stage Approaches 76
Key findings 76
Overview of early-stage innovative projects 76
TRAIL 77
Insulin-like growth factor receptor (IGFR) 78
MAP kinase pathway 79
The future of treatment of colorectal cancer (CRC) 79
Molecular markers will become an important part of therapy for patient selection 79
The future will see more combination therapies to target multiple pathways 80
Increased understanding of cancer evolution should result in a large range of potential drug targets 80
Bibliography 81
Journals 81
Websites 86
Datamonitor reports 88
APPENDIX 90
Methodology 90
Epidemiology forecasts 90
Product forecasts 90
Datamonitor drug assessment scorecard 91
Contributing experts 92
About Datamonitor 93
About Datamonitor Healthcare 93
About the Oncology analysis team 93
Datamonitor consulting 94
Disclaimer 94

LIST OF TABLES
Table 1: Sales forecasts for late-phase colorectal cancer (CRC) pipeline products in the seven major markets ($m), 2009-2018 4
Table 2: Drugs in late-phase development for colorectal cancer (CRC), 2009 9
Table 3: Sales forecasts for late-stage colorectal cancer (CRC) pipeline products in the seven major markets ($m), 2009-2018 10
Table 4: Amgen's marketed and pipeline oncology portfolio, 2009 13
Table 5: AstraZeneca's marketed and pipeline oncology portfolio, 2009 14
Table 6: Roche's marketed and pipeline oncology portfolio, 2009 16
Table 7: Forecast incidence of colorectal cancer (CRC) in the seven major pharmaceutical markets, 2009-2018 23
Table 8: Molecular targeted therapies (MTTs) approved for use in metastatic colorectal cancer (CRC), 2009 27
Table 9: Eloxatin (oxaliplatin) - drug profile, 2009 30
Table 10: Ability of Eloxatin to meet unmet needs in the first-line treatment of metastatic colorectal cancer (CRC), 2009 32
Table 11: Ability of Eloxatin to meet unmet needs in the second-line treatment of metastatic colorectal cancer (CRC), 2009 32
Table 12: Drugs in late-phase development for colorectal cancer (CRC) , 2009 40
Table 15: Sales forecasts for late-phase colorectal cancer (CRC) pipeline products in the seven major markets ($m), 2009-2018 41
Table 16: Aflibercept - drug profile, 2009 43
Table 17: Aflibercept: key historical events 43
Table 18: Clinical development of aflibercept in colorectal cancer (CRC), 2009 45
Table 19: Ability of aflibercept to meet unmet needs in colorectal cancer (CRC), 2009 49
Table 20: Sales forecast for aflibercept in colorectal cancer (CRC) across the seven major markets ($m), 2009-2018 50
Table 21: Brivanib - drug profile, 2009 51
Table 22: Brivanib: key historical events 52
Table 23: Clinical development of brivanib in colorectal cancer (CRC), 2009 53
Table 24: Phase I results investigating a second-line or higher combination of Erbitux and brivanib in advanced gastrointestinal malignancies 54
Table 25: Ability of brivanib to meet unmet needs in colorectal cancer (CRC), 2009 58
Table 26: Sales forecast for brivanib in colorectal cancer (CRC) across the seven major markets($m), 2009-2018 59
Table 27: Recentin (cediranib) - drug profile, 2009 60
Table 28: Recentin: key historical events 61
Table 29: Clinical development of Recentin in colorectal cancer (CRC), 2009 62
Table 30: Ability of Recentin to meet unmet needs in colorectal cancer (CRC), 2009 66
Table 31: Sales forecast for Recentin in colorectal cancer (CRC) across the seven major markets ($m), 2009-2018 67
Table 32: MK-0646 - drug profile, 2009 68
Table 33: MK-0646: key historical events 69
Table 34: Clinical development of MK-0646 in colorectal cancer (CRC), 2009 70
Table 35: Ability of MK-0646 to meet unmet needs in colorectal cancer (CRC), 2009 74
Table 36: Sales forecast for MK-0646 in colorectal cancer (CRC) across the seven major markets, 2009-2018 ($m) 75
Table 37: Top 10 early-stage colorectal cancer (CRC) drug targets, 2009 77
Table 38: Datamonitor drug assessment parameters 91
List of Figures
Figure 1: Datamonitor drug assessment summary for molecular targeted therapies (MTTs) in development for colorectal cancer (CRC), 2009 5
Figure 2: Colorectal cancer (CRC) pipeline split by development phase and drug class, 2009 9
Figure 3: Datamonitor drug assessment summary for molecular targeted therapies (MTTs) in development for colorectal cancer (CRC), 2009 11
Figure 4: Incidence and mortality from colorectal cancer (CRC) in the seven major pharmaceutical markets, 2009 and 2018 23
Figure 5: Incidence of colorectal cancer (CRC) in the rest of the world, 2009 and 2019 24
Figure 6: Datamonitor drug assessment summary for molecular targeted therapies in development for colorectal cancer (CRC), 2009 39
Table 13: Forecast assumptions for molecular targeted therapy colorectal cancer (CRC) pipeline products across the seven major markets, 2009 40
Table 14: Forecast assumptions for molecular targeted therapy colorectal cancer (CRC) pipeline products across the seven major markets, 2009 41
Figure 7: SWOT analysis for aflibercept, 2009 44
Figure 8: Phase II data on the second-line treatment of aflibercept in recurrent metastatic colorectal cancer (CRC) patients following failure of standard therapy 46
Figure 9: Datamonitor drug assessment summary for aflibercept in colorectal cancer (CRC), 2009 49
Figure 10: Brivanib SWOT analysis, 2009 52
Figure 11: Retrospective analysis evaluating correlation between KRAS status and efficacy from a Phase I/II study of brivanib in combination with Erbitux in patients with advanced or metastatic colorectal cancer (CRC) 54
Figure 12: Datamonitor drug assessment summary for brivanib in colorectal cancer (CRC), 2009 58
Figure 13: SWOT analysis for Recentin, 2009 61
Figure 14: Phase II results for second-line FOLFOX + Recentin versus FOLFOX + Avastin in metastatic colorectal cancer (CRC) (HORIZON I) 63
Figure 15: Datamonitor drug assessment summary for Recentin in colorectal cancer (CRC), 2009 66
Figure 16: SWOT analysis for MK-0646, 2009 69
Figure 17: Phase II study of MK-0646 in second-line or higher metastatic colorectal cancer (CRC) patients with wild-type KRAS 71
Figure 18: Datamonitor drug assessment summary for MK-0646 in colorectal cancer (CRC), 2009 73
Figure 19: Early-stage colorectal cancer pipeline (CRC) split by drug class, 2009 76
Figure 20: Datamonitor drug assessment summary for molecular targeted therapies in development for colorectal cancer (CRC), 2009 92