Read the full press release from RPRD Diagnostics here.

 RPRD (Right Patient Right Drug) Diagnostics and St. Jude Children’s Research Hospital today announced their recent publication, “Challenges in clinical implementation of CYP2D6 genotyping: choice of variants to test affects phenotype determination,” in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics.

In this article the authors address the need to create comprehensive genotyping tests that go beyond the commonly identified genes affecting drug metabolism in those primarily of European descent to also cover clinically important genetic variants found across race and ancestry groups. In addition, the authors call for the industry standardization of genetic biomarkers and variants in clinical genotyping assays to aid clinicians in correctly prescribing and dosing drugs.

This article highlights a specific case, whereby a patient with sickle cell disease from a minority population has a CYP2D6 genetic variant.

The CYP2D6 gene is part of the P450 family of genes that codes for the enzymes known to be involved in metabolizing 25% of FDA-approved drugs used in the clinic. It is an important gene to understand; depending on a patient’s genetic makeup, CYP2D6 enzymes can induce or inhibit a drug’s effects. However due to its complex structure and surrounding pseudogenes, CYP2D6 is a very challenging gene to diagnose, and clinical testing platforms and labs are struggling with determining the accurate genotype.

Mary V. Relling, Pharm.D., pharmaceutical department chair at St. Jude’s, said, “Our findings indicate that not all CYP2D6 genotyping tests are alike; if tests don’t interrogate some alleles, patients could be assigned an incorrect drug metabolizer status.”

Genotyping on the patient was performed by multiple labs and resulted in different phenotype determinations. These conflicting results recommended different drug dosing strategies, which can risk patient safety through unanticipated adverse reactions or therapeutic failures.

Pharmacogenomics aims to optimize drug therapy based on the effect of genetic variations on drug response, and a growing list of biomarkers associated with drug response have been identified through genome wide association studies (GWAS). However, most of these studies have been conducted mainly in patients of European ancestry and do not always replicate in other populations.

Per Dr. Ulrich Broeckel, CEO and co-founder of RPRD, “This lack of diversity has contributed to a growing health disparity in precision medicine, with minorities underrepresented in these genotyping assays. RPRD recognized this disparity early on and has worked with various collaborators, including St. Jude’s, to develop comprehensive tests that correctly identify important genetic variants dealing with drug effects.” RPRD is the pharmacogenomics provider for the leading pediatric cancer centers in the nation, as ranked by U.S. News and World Report for 2019-2020.

In the described patient’s case, only RPRD’s Whole Pharmacogenomics Scan (WPSTM) included the variants, identified the patient as a poor metabolizer of the standard drug administered, and recommended correct dosing that will become part of the patient’s lifelong disease management strategy.

“At RPRD, our mission is to drive innovation in pharmacogenomics, resulting in more comprehensive tests that are inclusive of clinically important variants across a racially diverse population. We believe these variants must be standardized across the industry so any pharmacogenomics testing identifies the correct phenotype. Patient safety based on evidence-based research is foremost as we work toward the goal of truly personalized, precision medicine,” said Broeckel.