Pharmacogenomics for Clinical Trials of COVID-19 Medicines: Why Is This Important Now?

Historically, pharmacogenomics has origins in biochemical genetics in the 20th century and astute observations on unusual clinical responses to medicines. Extreme drug response phenotypes observed in the clinic have triggered molecular research on mechanisms of person-to-person variations in drug safety and efficacy (Kalow, 1962; Ozdemir et al., 2009), and paved the way for the contemporary field of pharmacogenomics.

As the pandemic evolves to an endemic disease, there is also an important corollary for the long game planetary health response aimed at coronavirus disease 2019 (COVID-19) medicines. Because medicines do not work in everyone, and side effects occur in some but not all persons, the emerging and ongoing clinical trials on COVID-19 medicines would benefit from incorporation of pharmacogenomics and biomarkers for precision medicine.

As pharmacogenomics begins to move to the center stage of COVID-19 drug design and development (Badary, 2021), including drugs that are being repurposed for COVID-19, pharmacovigilance signals during and after clinical trials can be detected much more effectively using pharmacogenomics (Sardas, 2010; Şardaş and Kendirci, 2019). Pharmacogenomic biomarkers are part of rational therapeutics. They support a public health vision by bringing drugs to the clinic that may otherwise not be available because of side effects that occur in a subpopulation, for example. Having pharmacogenomics biomarkers would allow prior testing of patients at risk for toxicity and thus help achieve safer use of medicines in general.

Proof-of-concept studies on COVID-19 drug candidates, too, can benefit from pharmacogenomics biomarkers, allowing testing of drugs in subpopulations that carry a more responsive drug target subtype. A proactive vision to include pharmacogenomics variations in drug targets and pharmacokinetics can potentially reduce the costs and duration of clinical trials (Ohashi et al., 2008).

Drug repurposing has been an active area of investigation since the beginning of the pandemic. Pharmacogenomic variation in molecular targets of repurposed drugs, not to mention in their pharmacokinetic pathways, should be integral considerations for decision making in choice of the drug candidates optimally suited for repurposing against treatment and/or prevention of COVID-19.

Pharmacogenomic biomarkers offer a conceptual and practical steering wheel and prospects to design clinical trials for new COVID-19 medicines. As we continue to learn more on the virus and strategies to fight COVID-19 broaden to medicines, now is a good time to bring pharmacogenomics and precision medicine biomarkers online, preferably beginning with clinical trial designs. It would also be prudent to think of drug development in a context of systems ecology (Sardas et al., 2020), as many natural compounds serve as sources for drug discovery and biomarkers could help triage the natural compounds that are more likely to serve as COVID-19 drug candidates in humans.

COVID-19 is a systemic disease with effects including and beyond the lung. Long-term effects and complications of the disease remain as formidable threats for a new wave of chronic diseases in the coming decade, an area where therapeutics innovation will be much needed, and where pharmacogenomics is poised to make significant contributions to enable drug discovery, rational design of clinical trials and drug repurposing.

Insofar as measuring pharmacodynamic effects of COVID-19 medicines is concerned, the new field of phenomics 2.0 offers the promise of capturing drug-related outcomes in real time for pharmacogenomics association analyses, and in ways contextualized within the real life settings of patients. OMICS has previously featured the concept of the Internet of Pharmaceutical Things (IoPT) that fuses process innovation with experience innovation to capture a broad range of high-throughput phenotypes that are relevant to current development efforts for innovative COVID-19 medicines (Özdemir, 2020). IoPT also has potential for applications toward automation in pharmacy services in a context of a comprehensive systems medicine response to COVID-19.

Pharmacogenomics is well poised to inform the development of a broad range of preventive and therapeutic options in the clinic, the pharmacy, and planetary health practice. We should also bear in mind that COVID-19 vaccines and medicines are planetary public goods (Von Schomberg and Özdemir, 2020). Every effort should be made for universal access to COVID-19 vaccines and future medicines in all world populations in the global North and the global South.