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DESCRIPTIONA complete business plan with extended analysis of Stratified Medicine in market base as well in translational research base.
- 1.Stratified and Personalized Medicine:An overview
2. Table of contents Executive summary p. 3 Context, definitions and benefits to Stakeholders p. 6 The role of biomarkers & diagnosticsp. 13 Market breakdownp. 22 Main marker drivers p. 30 Key challengesp. 41 Commercial subsector overview p. 50 Overview of translational research base p. 72 Summary and conclusions p. 84 1 3. Objectives of Insight Report The purpose of this Insight report is to provide a broad overview of stratified medicine covering themain markets, technologies, and clinical and technology market drivers. It will describe relevant Scottish strengths in both the academic and the company subsectorsimpacted by stratified & personalized medicine. This report will focus primarily on the more immediate market opportunities in mainstream basedstratified medicine using of specific genomic, proteomic and imaging biomarkers. It will also anticipate future developments in the transition to fully personalized medicine based onwhole genome sequencing of patient genomes.2 4. Executive Summary Stratified and personalized medicine are two related sectors of great immediate and long termsignificance to the health and competiveness of the Scottish medical and life sciences sector. Thisapplies across the board to the NHS, academic research base and key sectors of the life sciencecompany landscape most notably CROs, diagnostics, research tools and IT/bioinformatics. Stratified medicine describes the current transitional situation where patient populations are nowincreasingly stratified during drug discovery clinical trials using a range of biomarkers. Some of thediagnostic biomarkers subsequently become companion diagnostics mandated and co-marketedwith the therapy. At the moment the bulk of the market of around $20 billion p.a. resides in the provision ofbiomarkers, with associated products and services, for drug discovery as opposed to post market-launch products co-marketed with the therapy. The benefits of stratified medicine are reduced time and cost of drug discovery and more targetedefficacious drugs which have fewer side effects. When the biomarker use is extended to clinical practice, NHS and healthcare providers also benefitfrom overall reduced costs from better drug treatment and patient disease management. Personalized medicine anticipates a future where a much greater amount of information is available,in particular patient specific whole genome data, to inform and personally tailor and target theselection of more therapies to the specific needs of the patient. 3 5. Executive Summary The advent of stratified medicine, which uses only a small fraction the potential available genomicand other omic biomarkers has already been profound. It has produced a very rapid convergence of diagnostics and therapeutics companies facilitatingmajor pharma and in vitro diagnostics collaborations. There has been hugely increased emphasison new biomarker discovery and validation in both research and commercial sectors. The very process of drug discovery itself is now significantly dependent upon response monitoringbiomarkers which may evolve into marketed companion diagnostics. These changes have createdmajor new challenges and opportunities for CRO service companies and hugely increased demandfor effective IT and bioinformatics services. The delivery and economics of medicine itself, particularly the integration of genomic and other datato create much more tailored and individualized treatments is having to be reexamined withparticular emphasis on data security. 4 6. Executive Summary All of these trends are set to intensify as the plummeting cost of sequencing make the widespreadavailability of affordable whole genome sequencing a technical reality within the medium ratherthan long term. The very recent announcement by Life Technologies of the provision of a system which can delivera whole genome sequencing solution for $1,000 Genome vividly illustrates the very high rate oftechnical progress which is driving this field. Scotlands life science and medical landscape mix of leading translational research, strong in vitrodiagnostic, pharma, CRO and research tools companies means that it will be increasingly affectedby these trends. It is clear that the future international competiveness of the translational research base and the longterm profitability of major life sciences subsectors will be significantly affected by their response tothe major challenges and opportunities presented by Stratified and Personalized Medicine. It is also clear that given the strength of this research base and the the well established corporateand SME base in multiple key subsectors (notably research tools, IVD, pharma with CROs &imaging), stratified and personalized medicine represents a major strategic opportunity forScotland. 5 7. Context, Definitionsand Benefits to Stakeholders 8. Definitions I There is unfortunately no universally agreed definitions in this emergent area with the termsPersonalised Medicine Theranostics and Stratified Medicine all being to a large extentinterchangeably. Personalized medicine : a tailored approach to patient treatment Based on the molecularanalysis of genes proteins and metabolites Davis Nature Drug Discovery 2009 Personalized tailored or stratified medicine : these therapies combine a drug with acompanion diagnostic to select or exclude patients for treatment. ... By targeting patients on thebasis of distinctive biological characteristics enriched subpopulations that respond differently totreatment are identified thereby generating more favourable benefit risk profiles Trusheim et alNature Reviews 2011 Personalized medicine : the tailoring of medical treatment to the individual characteristics ofeach patient. It does not literally mean the creation of drugs or medical devices that are unique to apatient, but rather the ability to classify individuals into subpopulations that differ in theirsusceptibility to a particular disease or their response to a specific treatment. Preventive ortherapeutic interventions can then be concentrated on those who will benefit, sparing expense andside effects for those who will not. ... Critically, it also involves the development, validation and useof companion diagnostics to achieve the best outcomes in the management of a patients diseaseor their predisposition ABPI UK White Paper 2009 Predicting in advance which groups of patients will respond to a particular therapy andproviding treatment accordingly is known as stratified medicine (or personalized medicine) Stratified Medicine in the UK Vision and Roadmap TSB 2011 7 9. Definitions II In this report the following broad terms will be used: Stratified medicine: the process of using biomarkers to select groups of patients for clinical trials is called stratification and the science thereof labelled stratified medicine . These biomarkers are used in to monitor response for the purposes of evaluation of a response further upstream and earlier in the drug discovery process. Biomarkers used for such response evaluation in clinical trials may progress to become companion diagnostics co-marketed with the drug. Using this definition stratified medicine includes biomarkers used in the drug discovery process as this constitutes the largest market of relevance to Scottish companies and researchers. It is also in effect a pipeline of new biomarkers platforms and services of which only some will migrate eventually into the clinic. Companion diagnostics: (CDx) will refer to the diagnostic test that has been developed for a specific therapy and the combination of the specific therapy (Rx) and companion diagnostic. These specific (Rx-Dx) have usually been developed in parallel and have passed through the regulatory process as a package. The clinical use of the therapy requires the use of the specific diagnostic test. At the present time this is most commonly a molecular diagnostic test and drug. However other more physiological based diagnostic modalities (i.e. imaging) and non drug therapies (i.e. radiation, surgery, rehabilitation, nutrition/wellness) in principle fall within this category. Personalised medicine: is in effect the ultimate destination for stratified medicine enabling a very high level of tailoring of therapeutic intervention to the unique genetic make-up of the patient. It will use many of the techniques and processes developed at a group level in stratified medicine. One of the defining medium term features of personalised medicine will be the availability of full genome sequence data of the individual patient. 8 10. Stratified & Personalised Medicine is a Continuum Stratified and personalised medicine are positioned on a continuum rather than discrete processesthat can be neatly defined. The diagram below attempts to convey this and the possible future trends. Landmark Exemplar Therapies New Chemical Entities BiologicsMonoclonalsStratified TherapiesNon-genomic stratified medicine: Zantac IbuprofenVioxx Epogen AvasitinHercetptin .. ? Proteomics & advanced imaging Genomic personalized medicine: Personal and Affordable Genomics becomes a commercial reality and increasingly influences all treatments options. Stratified medicine: Genomic and other biomarkers increasingly used in the drug discovery process and some pioneering companion diagnostics launched. One size fits all blockbuster drugs become rare commercial exception.Conventional medicine: Blockbuster or one size fits all drugs prescribed to all patients diagnosed with a specificdisease. This is associated with relatively high rates of non-efficacy and adverse effects due to lack or predictive biomarkersduring the discovery process of companion diagnostic post launch.Key genomic advancesPCRSNPs Human genome sequenced under $1000 genomeis feasible > deployed > exploited19801990 2000 201020202030 9 11. Stratified Medicine in Context: Biomarkers The general trends