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Integrating Pharmacogenetics Into Society: in Search of a Model

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Integrating Pharmacogenetics Into Society: in Search of a Model F OCUS ON PHARMACOGENETICS 29. Jones, B. C. et al. Quantitative-trait loci Acknowledgements and selling a range of specialist services to analysis of cocaine-related behaviours and Supported by National Institutes of Health grants. neurochemistry. Pharmacogenetics 9, 607–617 the pharmaceutical industry. This core Competing interests statement (1999). group is described in TABLE 1.Most of these 30. Port, J. D. & Bristow, M. R. Altered β-adrenergic The author declares no competing financial interests. receptor gene regulation and signaling in chronic heart firms have been formed since 1997 and are failure. J. Mol. Cell Cardiol. 33, 887–905 Online Links mainly located in the United States. Between (2001). 31. van Campen, L. C., Visser, F. C. & Visser, C. A. DATABASES 1997 and 2000, there was a steady growth in Ejection fraction improvement by β-blocker treatment The following terms in this article are linked online to: in patients with heart failure: an analysis of studies Entrez Gene: http://www.ncbi.nlm.nih.gov/entrez/ the number of small to medium enterprises published in the literature. J. Cardiovasc. Pharmacol. query.fcgi?db=gene working with PGx. However, in 2001 this 32 Suppl. 1, S31–S35 (1998). ADRB1 | ADRB2 | CFTR | CYP1A2 | CYP2D6 | CYP2E1 | 32. Mason, D. A., Moore, J. D., Green, S. A. & CYP3A4 | TPMT | growth slowed, and in 2002 consolidation of Liggett, S. B. A gain-of-function polymorphism in a OMIM: http://www.ncbi.nlm.nih.gov/entrez/ the sector started to take place, with five β query.fcgi?db=OMIM G-protein coupling domain of the human 1- adrenergic receptor. J. Biol. Chem. 274, cystic fibrosis mergers and acquisitions of small PGx firms 12670–12674 (1999). Access to this interactive links box is free online. between 2001 and 2002. Secondly, there are about 30 large pharma- ceutical companies who are investing in PGx, either internally or through collaborations SCIENCE AND SOCIETY with smaller PGx firms. The main players — primarily global firms — are listed in BOX 1. GlaxoSmithKline, Roche and Pfizer are among Integrating pharmacogenetics into the larger investors in this technology. How- ever, it should be stressed that investment by major pharmaceutical companies can be mea- society: in search of a model sured along a ‘spectrum’ of commitment, with some companies more committed to PGx than Andrew Webster, Paul Martin, Graham Lewis and Andrew Smart others, at this point in time. In addition to these two main groups, a number of specialist Abstract | There has been considerable Health Pharmacogenetics Research Network, diagnostic companies (for example, Beckton scientific, corporate and policy interest in as well as among national health policy agen- Dickinson) and US health-care providers (for the more effective use of genetics in cies, as indicated by the UK government’s example, Kaiser Permanente) are also investing both drug development and delivery. recent White Paper on the introduction of in the technology through the formation of Pharmacogenetics — the study of the PGx (and other genetic techniques) into the collaborations with smaller firms. relationship between an individual’s genetic health service2. Since the first collaboration on PGx makeup and response to medicinal drugs — PGx is on the threshold of making a major between Genset and Abbott in 1997, a fur- has attracted global interest, but will it live up impact in commercial labs and in the clinic. ther 180 industrial alliances have been to its promise? Looking beyond the hype that But, despite its promise and the heavy invest- formed around the technology. A similar has accompanied much of the commentary ment made in the technology, many compa- pattern to the growth of dedicated firms can in the area, the future of pharmacogenetics nies still question whether there is a coherent be seen, with a steady increase in the number will depend on how competing interests and business, health policy or regulatory model of collaborations until 2001, followed by a options are resolved. emerging to shape the future development of declining rate of growth (FIG. 1).This pattern PGx. Here, on the basis of detailed research indicates that some of the momentum behind Pharmacogenetics (PGx) is concerned with conducted on the social, economic and reg- the technology might have plateaued recently, understanding and, in the clinical setting, ulatory factors shaping PGx during the past partly because of complications in getting it managing the relationship between genetic 2 years (P.M., G.L., A.S. and A.W., False to ‘work’ effectively, and partly as a result of a variation and an individual’s response to med- Positive? The Clinical and Commercial stabilizing of investment3. icinal products. It provides the possibility of Development of Pharmacogenetics,The targeting drugs according to a person’s genetic Wellcome Trust report, also see Online links Options for the development of PGx. There is make-up — so-called ‘personalized medicine’ box), we aim to provide at least a partial no single or principal model for adopting — although it will probably be used to stratify answer to this question. After reviewing PGx technology. Instead, the development of patient populations into groups determined PGx in the commercial sector, and identify- the field can be understood in terms of a by their genotype1.Stratification along these ing the different strategies being pursued, process of experimentation and the search for lines might significantly improve the develop- we discuss its likely clinical role, the regula- viable techniques, with the technology being ment, testing and use of drugs. However, real- tory regime that is emerging, and the wider applied at multiple points in the drug discov- izing these benefits will depend on the policy implications that it raises, especially ery and development process. We have identi- development of viable commercial strategies for advanced health-care systems. fied five broad innovation options for the and clinical delivery in the next few years. It application of PGx (BOX 2). might also require new approaches to regu- The development of PGx technology The first of these is aimed at improving the lation, drug approval and PHARMACOVIGILANCE at Who is developing PGx? There are two discovery of new drugs. Options 2 and 3 are national and international levels. broad groups involved in the commercial mostly concerned with using PGx to improve Given its potential, PGx has gained con- development of PGx. Firstly, about 30 small the safety and efficacy of prospective drugs siderable interest in the pharmaceutical biotechnology and genomics firms are through the re-design of clinical trials. Finally, industry and among clinical researchers — involved in conducting PGx association PGx is also being used to improve the safety such as in the US-based National Institutes of studies, developing specific genetic tests, and efficacy of medicines that have already NATURE REVIEWS | GENETICS VOLUME 5 | SEPTEMBER 2004 | 663 © 2004 Nature Publishing Group PERSPECTIVES Table 1 | Biotechnology and genomics companies developing pharmacogenetics individuals’ genetic profiles as part of the US Food and Drug Administration (FDA)- Company Founded Location Focus imposed post-marketing commitments. This Acadia Pharmaceuticals 1997 US Pharmacogenomic drug discovery in psychiatry PGx-based research involves the prospective collection and analysis of samples from addi- Affymetrix 1992 US Gene chips for pharmacogenetic applications tional trials. The aim of this research is to identify SNPs or haplotypes that can predict Axis-Shield 1982. UK Clinical diagnostics adverse events in patients and to determine Celera Diagnostics 2000 US Clinical PGx diagnostics the genotype of polymorphic cytochrome Curagen 1996 US PGx association and toxicogenomic protein 450 (CYP450) enzymes that are studies responsible for the drug’s metabolism (REF.7, DeCODE (Encode) 1996 (1999) Iceland Clinical PGx diagnostics and Roses, A., unpublished data). (pharmacogenomics CRO) Specialist diagnostics firms and health- DiaDexus 1997 US Clinical PGx diagnostics care providers show the greatest interest in the DNAPrint Genomics 2000 US Clinical PGx diagnostics pre-prescription genotyping of patients, to DxS 2001 UK PGx genetic analysis services improve the safety and efficacy of established Epidauros 1997 Germany PGx assays and services products and the development of drug-test Epigenomics 1998 Germany Clinical PGx diagnostics combinations. Both aims offer the prospect of new diagnostics markets and reduced health- Exon Hit Therapeutics 1997 France Clinical PGx diagnostics care costs. Although this might point to a First Genetic Trust 2000 US Genetic banking services clear business model, the situation is more Gaifar 1997 Germany Clinical PGx diagnostics (viral complicated in relation to the development of genotyping) new products, as larger firms will inevitably be GAG Biosciences 2000 Germany PGx genotyping services involved. New drugs that are developed using Genaissance 1997 US PGx services and diagnostics stratified clinical trials on the basis of PGx tests Gene Logic 1994 US Toxicogenomic serivces will often require a dedicated drug-test combi- Genelex 1987 US Direct to consumer PGx testing nation to be licensed. In such cases, it is in the Genomics Health 2000 US PGx patient testing services interests of pharmaceutical companies to undertake drug-test development, either Genset (Serono) 1989 France Association studies of drug (Switzerland) response themselves or through collaboration with specialist
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