Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels (2000-2020).

Jeeyun A Kim,Christine Y Lu,Rachel Ceccarelli

doi:10.3390/jpm11030179

Jeeyun A Kim, Christine Y Lu + Show 1 more

Open Access

https://doi.org/10.3390/jpm11030179

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Abstract

Pharmacogenomics (PGx) is a key subset of precision medicine that relates genomic variation to individual response to pharmacotherapy. We assessed longitudinal trends in US FDA approval of new drugs labeled with PGx information. Drug labels containing PGx information were obtained from Drugs@FDA and guidelines from PharmGKB were used to compare the actionability of PGx information in drug labels across therapeutic areas. The annual proportion of new drug approvals with PGx labeling has increased by nearly threefold from 10.3% (n = 3) in 2000 to 28.2% (n = 11) in 2020. Inclusion of PGx information in drug labels has increased for all clinical areas over the last two decades but most prominently for cancer therapies, which comprise the largest proportion (75.5%) of biomarker–drug pairs for which PGx testing is required. Clinically actionable information was more frequently observed in biomarker–drug pairs associated with cancer drugs compared to those for other therapeutic areas (n = 92 (59.7%) vs. n = 62 (40.3%), p < 0.0051). These results suggest that further evidence is needed to support the clinical adoption of pharmacogenomics in non-cancer therapeutic areas.

Highlights

80% of the variability in drug efficacy and adverse effects can be explained by genomic variation, which creates major challenges for the appropriate selection and dosing of medications [1]
This study examined trends in Food and Drug Administration (FDA) approvals of new drugs labeled with PGx information from 2000 to 2020
Of 694 total new drug approvals identified from 1 January 2000 to 31 July 2020, new molecular entities accounted for 75.9% (n = 527) and biologics represented 24.1% (n = 167)

Summary

Introduction

80% of the variability in drug efficacy and adverse effects can be explained by genomic variation, which creates major challenges for the appropriate selection and dosing of medications [1]. As an applicable component of precision medicine, pharmacogenomics (PGx) incorporates genomic profiling to identify biomarkers based on relevant genotype–phenotype interactions that can predict drug response and risk of adverse drug reactions for individual patients. Key somatic variants, such as the overexpression of ERBB2 in breast cancer, can serve as markers for the selection of patient groups for which drugs like adotrastuzumab emtansine and talazoparib tosylate are indicated. Pharmacogenomic testing for germline variants, such as those in the DPYD gene, can predict the risk of toxicity and differential response to cancer therapies such as 5-fluorouracil, enabling prescribers to better tailor therapies with greater efficacy and safety for patients [5,6]. PGx biomarkers have been used to specify dosing alterations, as in the example of the CYP2C9 and VKORC1 variants in warfarin use for treatment and prevention of thromboembolic events, as well as to prevent the occurrence of severe hypersensitivity effects, as with an HLA-B variant in relation to abacavir use for treatment of HIV infection [3,7]

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