Application of Multiplex Biomarker Approaches to Accelerate Drug Discovery and Development
Multiplex biomarker tests are becoming an essential part of the drug development process. This chapter explores the role of biomarker-based tests as effective tools in improving preclinical research and clinical development, and the challenges that this p
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Introduction Pharmaceutical companies are under pressure to improve their returns on existing and novel drug discovery efforts. This is an almost impossible task, considering that the average drug costs approximately one billion US dollars to develop and takes 10–15 years from initial discovery to the marketing phase [1]. This problem is compounded by the fact that around 70 % of drugs do not recover their research and development costs and approximately 90 % fail to yield an adequate return on investment. In addition, fewer than one in ten new drugs entering clinical trials make it to the market and some of those that do make it experience withdrawal and/or litigation [2–5]. Therefore, in order for the pharmaceutical companies to survive, minimizing these risks has become one of the most important objectives in drug discovery projects in recent years. For example, there has been considerable effort aimed at establishing standard operating procedures to plot a course through these problems and to help meet the intimidating regulatory demands. But the regulatory agencies have not just been standing by idling watching. In order to assist pharmaceutical
Paul C. Guest (ed.), Multiplex Biomarker Techniques: Methods and Applications, Methods in Molecular Biology, vol. 1546, DOI 10.1007/978-1-4939-6730-8_1, © Springer Science+Business Media LLC 2017
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Hassan Rahmoune and Paul C. Guest
companies in this process, they have encouraged the incorporation of biomarker-based tests into the drug discovery pipeline and the Food and Drug Administration (FDA) has initiated efforts to modernize and standardize all involved procedures to facilitate delivery of more effective and safer drugs [6]. The FDA has estimated even a 10 % improvement in the ability to predict failure of drug before it enters the clinical trial phases could save as much as one hundred million US dollars in development costs per drug [7].
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A Brief History of Failed Drugs The need for biomarker tests to guide drug development is perhaps best seen by recent major failures in this process. Over the last two decades more than 30 drugs have been withdrawn, mainly as a result of hepatotoxic or cardiotoxic effects [8]. In 1997, the FDA recommended that the antihistamine drug Terfendine be withdrawn from the market due to an association with heart arrhythmia, which could increase the risk of heart attacks and death [9]. In the year 2000, the antidiabetic and anti-inflammatory drug Troglitazone was withdrawn due to reports of liver toxicity [10]. In 2001, the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor Cerivastatin, developed to treat high cholesterol levels, was withdrawn due to an increased risk of rhabdomyolysis, a severe condition that causes muscle pain and weakness and can sometimes result in renal failure and death [11, 12]. In 2003, the antidepressant drug Nefazodone was withdrawn due to liver toxicity [13]. One of the most infamous cases was the withdrawal of the antiinflammatory drug Vioxx by Merck, due to reports about its increased
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