Executive summary 10
Introduction to drug-diagnostic co-development 10
Regulatory challenges 11
Commercial challenges 12
Emerging business models 13
Rx-Dx collaborations 14
Future trends 15

Chapter 1 Introduction to drug-diagnostic
co-development 18
Summary 18
Introduction 19
Technology driving change 19
Biomarkers & personalized medicine 20
Convergence of players 22
The role of Dx in personalized medicine 23
Targeted therapeutic developments 25
New industry partnerships 26
Companion test development models 27

Chapter 2 Regulatory challenges 32
Summary 32
Introduction 33
US regulatory landscape 34
Voluntary genomic data submissions (VGDS) 34
Rx-Dx co-development guidance 34
IVDMIA guidance 35
Dx usage determines risk 37
Study design 40
EU regulatory process 41
IVD regulatory framework under discussion 41
Pharmacogenomics in drug development 42
Potential advantages of the EU system 43
Case Study: K-RAS 44

Chapter 3 Key commercial challenges 48
Summary 48
Introduction 49
Reimbursement 50
Information requirements 51
European situation 52
Case Study: Oncotype DX 52
Role of health economics 54
Third-party studies 55
Clinical use 57
Different clinical settings 58
Intellectual property 59

Chapter 4 Emerging business models 62
Summary 62
Introduction 63
One-stop shop 63
Case Study: Roche 66
Acquisitions 66
Alignment of business areas 67
Companion Dx programs 69
Rx-Dx industry partnerships 70
Drivers of co-development partnerships 71
Types of agreements 72
Case Study: Pfizer-Monogram Biosciences 73
Collaborations underway 76

Chapter 5 Rx-Dx collaborations 78
Summary 78
Introduction 79
Asuragen 81
Background 81
Collaboration 81
Merck & Co 81
BG Medicine 82
Background 82
Collaboration 82
Cordex Pharma 82
bioMérieux 82
Background 82
Collaboration 83
Ispen 83
Merck & Co 83
ADNA project 83
Celera 84
Background 84
Collaboration 85
Abbott 85
Merck & Co 85
Ipsen 86
Curidium 86
Background 86
Collaboration 86
Takeda 86
Dako 87
Background 87
Collaboration 87
OSI Pharmaceuticals 87
Genentech 87
Bristol-Myers Squibb 88
DxS 88
Background 88
Collaboration 88
Amgen 89
Roche Molecular Diagnostics 89
GE Healthcare 90
Background 90
Collaboration 90
Eli Lilly 90
Genomic Health 91
Background 91
Collaboration 91
Pfizer 91
Bristol-Myers Squibb and Imclone Systems 91
HistoRx 92
Background 92
Collaboration 93
Lilly 93
LabCorp 93
Background 93
Collaboration 93
ARCA biopharma 94
Vanda Pharmaceuticals 95
Medco Health Solutions 95
Monogram Biosciences 96
Background 96
Collaboration 96
Pfizer HIV partnership 96
Oncology 97
OncoMethylome Sciences 97
Background 97
Collaboration 97
Merck KGaA 98
Schering-Plough 98
GlaxoSmithKline Biologicals 98
Abbott 98
Source MDx 98
Background 98
Collaboration 99
Pfizer 99
XDx 99
Background 99
Collaboration 100
Bristol-Myers Squibb 100

Chapter 6 Future trends 102
Summary 102
Introduction 103
New paradigm for pharma R&D 104
Rx-Dx combinations in pipeline 105
Changing dynamics of the IVD industry 107
Biomarker discovery for existing drugs 108
Next generation tests 109
Conclusions 110
Appendix 112
Research methodology 112
Glossary 112
Index 114

List of Figures
Figure 1.1: Biomarker discovery is comparable to drug discovery 21
Figure 1.2: Convergence of drug and diagnostic industries 22
Figure 1.3: Main therapy areas for Rx-Dx co-development (number of diagnostic tests) 27
Figure 1.4: Ideal Rx-Dx co-development scenario 28
Figure 1.5: Alternative co-development scenarios 29
Figure 2.6: Regulatory pathways for diagnostics in the US 36
Figure 2.7: Problems when patient accrual is gated via non-final IVD 39
Figure 3.8: Pre and post-approval challenges of Rx-Dx co-development 49
Figure 3.9: Difference between obtaining reimbursement in US and Europe 52
Figure 4.10: Roche Group sales by type (% of revenues), 2008 67
Figure 4.11: Diagnostic input for pharma projects 68
Figure 4.12: Rx-Dx partnership opportunities 70
Figure 6.13: Biomarker R&D expenditure ($bn), 2003 vs 2009 105
Figure 6.14: Forecast sales in IVD market ($bn), 2007-2012 107

List of Tables
Table 1.1: Drugs for which testing is recommended/required in the US 25
Table 1.2: Co-developed Rx-Dx combinations on market 26
Table 4.3: Biomarker strategy for Phase I/II oncology drugs 68
Table 4.4: Summary of Rx-Dx Co-Development Projects 76
Table 5.5: Rx-Dx co-development projects under review 80
Table 6.6: Patient population in whom selected drugs do not work (% population) 103