FDA Pharmacogenomic Biomarkers in Drug Labels

The list of pharmacogenomic biomarkers included the labels of FDA approved drugs has grown substantially over the last 10 years.  The most recent update from the FDA (Table of Pharmacogenomic Biomarkers in Drug Labels; 08/25/2011) lists 109 pharmacogenomic biomarkers included in the labels of 97 drugs (the labels of some drugs such as Imatinib and Warfarin include more than one pharmacogenomic biomarkers).

From a regulatory perspective, these biomarkers can be included in different sections of the drug labels (e.g. box warning, contraindication, clinical pharmacology), informing the prescribing physicians and the patients about identification of responders / non-responders, avoiding adverse events, and optimizing drug dosage.  The label information about pharmacogenomic biomarker can describe:

• Drug exposure and clinical response variability
• Risk for adverse events
• Genotype-specific dosing
• Mechanisms of drug action
• Polymorphic drug target and disposition genes

Functionally, the majority of the pharmacogenomic biomarkers currently included in the label of approved drug fall into the category of safety and efficacy markers related to drug exposure due to altered drug metabolism.  Indeed, 60 of the 109 pharmacogenomic biomarkers belong to the liver cytochrome P450 enzymes (CYP) which play a critical role in drug metabolism.  Other functional variants of enzymes involved in drug metabolism such as dihydropyrimidine dehydrogenase (DPD) and thiopurine S-methyltransferase (TPMT) also fall into this category. 

Although still representing a minority of cases, the number of drug efficacy pharmacogenomic biomarkers included in cancer drug labels has been growing (i.e. response biomarkers, predictive biomarkers).  In general, these biomarkers are designed to assist in the prescription decision by testing for the presence of the drug target. 

Examples:

• Imatinib: C-kit, BCR-Abl, PDGFR
• Trastuzumab: Her2/neu
• Vemurafenib: BRAF
• Tositumomab: CD20

As the field of biomarker development in support of drug development evolves, it is expected that this list of pharmacogenomic biomarkers included in drug labels will grow substantially, making the promise of personalized medicine a reality.

Thierry Sornasse for Integrated Biomarker Strategy