By Jeff Alfonsi, Sara Henderson, Peng Hsiao and Richard B. Kim
In 2012, the U.S. Food and Drug Administration approved a new cystic fibrosis (CF) medication called Kalydeco (ivacaftor). The approval of Kalydeco was significant because it targeted one of the causal genetic mutations rather than a more traditional approach focused on symptom relief. Furthermore, the Cystic Fibrosis Foundation created a registry where patients could contribute their genetic information, which helped researchers identify the target for Kalydeco. This story represents a major shift in the development of more targeted and individualized therapeutic agents.
Personalized, or precision, medicine is defined (PDF) by the National Academy of Sciences as “the use of genomic, epigenomic, exposure, and other data to define individual patterns of disease, potentially leading to better individual treatment.” Many examples of personalized medicine lie in pharmacogenomics, how an individual’s genetics impact the processes governing drug absorption, distribution, metabolism, and elimination. A number of commonly occurring genetic polymorphisms in cytochrome P-450 (CYP) enzymes reduce the rate by which drugs are metabolized in the body, resulting in drug accumulation, while extra copies of the gene may increase the metabolism of the drug and reduce systemic exposure and therapeutic benefit. Similarly, certain genes encode for transporter proteins that mediate the movements of drugs in and out of the cells. Genetics variations in transporters may leads to unexpected side effects or toxicity of the drugs. In additional to metabolizing enzymes and transporters, variations in drug targeted receptor expression may affect the drug efficacy of a given drug in an individual.
Since 2008, our team at the London Health Sciences Centre has offered personalized medicine-based treatment options for our patients at risk for harm as well as loss of benefit from a number of drugs in clinical use. Our personalized medicine team takes this description a step further: The personalized medicine approach represents the integration of a patient’s genetics, dietary, and environmental influences, as well as clinical or disease conditions, to identify more precise treatment options.
The cover article in the April issue of the AAPS Newsmagazine reviews how personalized medicine offers significant advantages compared to one-size-fits-all drug treatments in terms of efficacy and safety. Read Precision Medicine and Drug Development: Importance of Drug Transporters and Metabolizing Enzymes, from the AAPS Pharmacokinetics, Pharmacodynamics, and Drug Metabolism section, and then participate in the discussion point below.
What are the risks and benefits to incorporating genomics-guided drug selection or dosing during the drug development process?