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The Commercial & Clinical Development of Pharmacogenetics

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The Commercial & Clinical Development of Pharmacogenetics TheFalse commercial Positive? & clinical development of pharmacogenetics Paul Martin, Graham Lewis, Andrew Smart & Andrew Webster False positive? The clinical and commercial development of pharmacogenetics Paul Martin IGBiS, University of Nottingham Graham Lewis SATSU, University of York Andy Smart Bath Spa University Andrew Webster SATSU, University of York Acknowledgements This research was supported by a Wellcome Trust Biomedical Ethics programme project award (Ref No: 018381) on The Clinical and Commercial Development of Pharmacogenetics held by Paul Martin (Principal Investigator), Alison Pilnick and Andrew Webster. The original research was carried out between 2001-03, but data in this report has been updated with data collected as part of the authors’ involvement in the following projects: 1) A study Realising the Potential of Genomic Medicine undertaken by Paul Martin and Michael Morrison funded by the Royal Pharmaceutical Society; 2) A recent ESRC Science in Society Programme project undertaken by Graham Lewis (Pharmacogenomics, diagnostic tests and clinician acceptance, Award No. RES-151-25-0049) for which he is Principal Investigator; 3) A European Commission funded report: Institute for Prospective Technological Studies (IPTS) (2005) Pharmacogenetics and Pharmacogenomics: state-of-the-art and potential socio-economic impacts in the EU. European Commission Joint Research Centre, Seville, Spain. In particular, some of the data in chapters 2 and 3 were collected as part of this work by Paul Martin and Graham Lewis. The authors would like to acknowledge the support of the following people who have helped in the management and execution of the project: Dr Alison Pilnick who was involved in establishing the project and advising on the drug case studies; Katie Coveny and Michael Morrison who helped update the industry analysis; and Martyn Pickersgill who drafted the executive summary. We would also like to express our thanks to Professor Munir Pirmohamed, University of Liverpool, and Dr Celia Brazell, GlaxoSmithKline, who commented on an earlier draft of the report. However, responsibility for the report’s contents rests entirely with the authors. Finally, special thanks are given to the many anonymous informants and interviewees we approached as part of the research and whose time and assistance made the project possible Correspondence relating to this report should be sent to Dr Paul Martin, IGBiS, West Wing, Law and Social Sciences Building, University of Nottingham, NG7 2RD. Email: [email protected] Further copies are available from the above address or it can be downloaded from www.nottingham.ac.uk/igbis/pgx/ or www.york.ac.uk/res/pgx/ ISBN No. 0-9553542-1-8 (978-0-9553542-1-2) Published November 2006 © 2006 Paul Martin, Graham Lewis, Andy Smart and Andrew Webster Table of contents Executive summary ................................................................................3 1. Introduction ....................................................................................3 2. The industrial development of pharmacogenetics ..................................4 3. The regulation of pharmacogenetics....................................................5 4. The clinical use of pharmacogenetics...................................................6 5. The development of health policy to support pharmacogenetics ..............7 6. Conclusions .....................................................................................8 7. Recommendations............................................................................9 Chapter 1 Introduction: Pharmacogenetics and ‘personalised medicine’ ........ 11 1.1 The promise of pharmacogenetics................................................... 11 1.2 The research project ..................................................................... 13 1.2.1 Aims of the research ............................................................... 14 1.2.2 Novel conceptual framework..................................................... 14 1.3 Options for development of pharmacogenetics.................................. 15 1.3.1 Different approaches to pharmacogenetics and their potential benefits ......................................................................................... 16 1.4 Structure of the report .................................................................. 20 Chapter 2 The Commercial Development of Pharmacogenetics .................... 21 2.1 The key role of industry................................................................. 21 2.2 Development of PGx by SMEs......................................................... 21 2.3 The emerging market for PGx - technical options being developed....... 23 2.4 The development of diagnostic products .......................................... 29 2.4.1 PGx tests for drug metabolism .................................................. 30 2.4.2 Anti-viral drug resistance testing............................................... 31 2.4.3 Cancer PGx testing (disease stratification).................................. 31 2.4.4 PGx tests for other diseases ..................................................... 32 2.4.5 Other applications of PGx ......................................................... 32 2.5 Industrial collaborations in PGx ...................................................... 35 2.6 The development of PGx by large companies.................................... 37 2.6.1 PGx collaborations involving large companies.............................. 38 2.6.2 Clinical development involving PGx............................................ 38 2.6.3 Products on the market ........................................................... 38 2.6.3 Interviews with company managers........................................... 43 2.7 Summary and conclusion............................................................... 43 Chapter 3 The regulation of pharmacogenetics.......................................... 45 3.1 The emerging regulatory regime..................................................... 45 3.2 Regulatory authorities encourage the adoption of PGx ....................... 48 3.3 PGx and clinical development ......................................................... 52 3.3.1 Toxicology and early clinical development................................... 54 3.3.2 Late clinical development ......................................................... 54 3.3.3 Pharmacovigilance and post marketing surveillance ..................... 55 3.4 PGx and labelling issues ................................................................ 55 3.5 PGx and diagnostic tests ............................................................... 59 3.6 Ethical issues raised by clinical development and use of PGx............... 61 3.7 Conclusion................................................................................... 63 Chapter 4 The adoption of PGx in clinical practice...................................... 65 4.1 Introduction ................................................................................ 65 4.1.1 Pharmacogenetics in principle and practice ................................. 65 4.1.2 Study design and methodology ................................................. 66 4.2 Case study 1: Clozapine ................................................................ 67 4.2.1 The drug and its treatment context ........................................... 67 4.2.2 Why PGx? .............................................................................. 68 4.2.3 Barriers facing clinical adoption................................................. 69 4.2.4 Summary............................................................................... 70 4.3 Case study 2: Warfarin.................................................................. 70 4.3.1 The drug and its treatment context ........................................... 70 4.3.2 Why PGx? .............................................................................. 71 4.3.3 Barriers facing clinical adoption................................................. 72 4.3.4 Summary............................................................................... 73 4.4 Case study 3: Thiopurines - 6 mercaptopurine (6-MP) & azathioprine .. 73 4.4.1 The drugs and treatment contexts............................................. 73 4.4.2 Why PGx? .............................................................................. 74 4.4.3 Barriers facing clinical adoption................................................. 75 4.4.4 Summary............................................................................... 76 4.5 Case study 4: Isoniazid ................................................................. 76 4.5.1 The drug and its treatment context ........................................... 76 4.5.2 Why PGx? .............................................................................. 77 4.5.3 Barriers facing clinical adoption................................................. 77 4.5.4 Summary............................................................................... 78 4.6 Conclusions ................................................................................. 78 4.6.1 Drivers .................................................................................. 78 4.6.2 Challenges ............................................................................. 79 4.6.2 Final comments ...................................................................... 80 Chapter 5 Developing policy to promote pharmacogenetics........................
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