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Pharmacogenomics and the FDA

By March 31, 2011Commentary

The Food & Drug Administration issued a draft guidance on Clinical Pharmacogenomics and early stage drug development.  Pharmacogenomics is the study of how the differential genetic makeup and genomic expression of individuals will affect their respond to various drugs.  As relationships are established, pharmacogenomic diagnostics are created that are companions to the use of the drug.  Those diagnostics also increasingly require FDA approval.  The current draft guidance, however, is designed solely to encourage manufacturers to consider what kind of genomic evidence they should gather as they develop products.

As the FDA guidance notes, genetic differences can affect many aspects of a disease and its treatment.  The most relevant genes for drug development include those related to pharmacokinetics–absorption, distribution, metabolism and excretion (ADME); those related to the drug’s intended and unintended targets and those related to disease likelihood or severity.  In a number of cases now information on pharmacokinetics either must or should be collected before dosing, for example with warfarin, and some drugs should only be used in individuals with certain genetic dispositions toward treatment response, for example, herceptin.  Many of these relationships, however, were discovered after the drug had been marketed.  Now the FDA would like to see those identified as early as possible.

Ideally, the FDA would like to see genetic studies done on all subjects in Phase I and Phase II trials, with the aim of identifying populations that should receive higher or lower doses due to ADME differences; populations that are more likely to respond to the drug; identifying the dose/response relationship for different genetic or biomarkers and identifying groups at high-risk for adverse events.  These studies should be done both in healthy volunteers and in patients with the relevant disease.  The guidance goes on to identify certain study design and statistical concerns.  This guidance represents another important step in the continued evolution of personalized medicine. (FDA Guidance)

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