Genome-Based Therapeutics Targeted Drug Discovery and Development: Workshop Summary (2012) / Chapter Skim
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2 The Current Landscape
2 The Current Landscape
Pages 5-16
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From page 5... ...
· The cost of therapeutic development has increased significantly over the past few decades while the success rate has remained unchanged, and many drug failures often occur after large investments have been made. · While targeted therapeutics may decrease market size, overall market share may increase, leading to a significant potential advantage for developing stratified medicines.
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From page 6... ...
It indicated an approaching ability to stratify populations based on genomic-based biomarkers, leading to better clinical development programs. Genomic data would reveal how individuals might respond to, be resistant to, or have adverse effects from a drug, creating the potential for personalized medicines.
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From page 7... ...
Garret FitzGerald of the University of Pennsylvania added that it has already been demonstrated that genetic information can be used to evaluate adverse drug effects. Studies designed specifically to determine whether particular gene variants can be used to identify individuals at particular risk have been successful for both lumiracoxib and abacavir and required only very small numbers of study participants to do so.
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Oncology KRAS Cevimeline Dermatology and Dental CYP2D6 Chlordiazepoxide and Psychiatry CYP2D6 Amitriptyline Chloroquine Anti-Infectives G6PD Cisplatin Oncology TPMT Citalopram (1) Psychiatry CYP2C19 Citalopram (2)
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Oncology FIP1L1-PDGFR Imipramine Psychiatry CYP2D6 Indacaterol Pulmonary UGT1A1 Irinotecan Oncology UGT1A1 Isosorbide and Hydralazine Cardiovascular NAT1; NAT2 Ivacaftor Pulmonary CFTR (G551D) Lapatinib Oncology Her2/neu Lenalidomide Hematology Chromosome 5q Letrozole Oncology ER &/PgR receptor Maraviroc Antivirals CCR5 Mercaptopurine Oncology TPMT Metoprolol Cardiovascular CYP2D6 Modafinil Psychiatry CYP2D6 Nefazodone Psychiatry CYP2D6 Nilotinib (1)
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Food and Drug Administration. BOX 2-1 Definition "Personalized medicine" or "stratified medicine," as used by speakers in the workshop, refers to the use of an individual's characteristics, including genetic information, to guide medical decisions regarding prevention, diagnosis, and treatment of disease.
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From page 11... ...
e Diagnostic Patient targets compliance patients d improves Underserved patients enter b c Preferred therapy for targeted patients Market share (%) FIGURE 2-1 A number of factors influence the market potential for targeted thera Figure peutics with the prospect of reduced 2-1.eps market size leading to increased market share.
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From page 12... ...
Furthermore, as Davies observed, failures often occur after large investments have been made. In 2010, 45 separate drugs failed in Phase III clinical trials, with the average cost for a Phase III trial being about $100 million.
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components in integrated circuits was doubling approximately every year. In the pharmaceutical industry, the output per billion dollars spent has consistently decreased by half every 9 years since 1952.
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In addition, regulatory constraints are getting tighter, which is an issue for thinking about innovative approaches to bringing medicines to market with companion diagnostics or a targeted approach. In general, Davies continued, the commercial model for the development of personalized medicines remains immature, with the commercial and marketing organizations within industry retaining a preference to go to market with a more general molecule than with a targeted therapeutic.
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From page 15... ...
For example, no candidate marker for response to bevacizumab has reached a level of performance acceptable to regulators, and genetic tests for warfarin response have not been widely adopted. FitzGerald added that while it is well established that genetic variants impact warfarin metabolism, there is little change in prescribing practices for testing largely because physicians are reluctant to move away from established measures of anticlotting effects.
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From page 16... ...
16 GENOME-BASED THERAPEUTICS not deliver the expected therapeutic breakthroughs" (Goldman, 2012)
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