Pharmacogenomic biomarker information differences between drug labels in the United States and Hungary: implementation from medical practitioner view

Abstract

Pharmacogenomic biomarker availability of Hungarian Summaries of Product Characteristics (SmPC) was assembled and compared with the information in US Food and Drug Administration (FDA) drug labels of the same active substance (July 2019). The level of action of these biomarkers was assessed from The Pharmacogenomics Knowledgebase database. From the identified 264 FDA approved drugs with pharmacogenomic biomarkers in drug label, 195 are available in Hungary. From them, 165 drugs include pharmacogenomic data disposing 222 biomarkers. Most of them are metabolizing enzymes (46%) and pharmacological targets (41%). The most frequent therapeutic area is oncology (37%), followed by infectious diseases (12%) and psychiatry (9%) (p < 0.00001). Most common biomarkers in Hungarian SmPCs are CYP2D6, CYP2C19, estrogen and progesterone hormone receptor (ESR, PGS). Importantly, US labels present more specific pharmacogenomic subheadings, the level of action has a different prominence, and offer more applicable dose modifications than Hungarians (5% vs 3%). However, Hungarian SmPCs are at 9 oncology drugs stricter than FDA, testing is obligatory before treatment. Out of the biomarkers available in US drug labels, 62 are missing completely from Hungarian SmPCs (p < 0.00001). Most of these belong to oncology (42%) and in case of 11% of missing biomarkers testing is required before treatment. In conclusion, more factual, clear, clinically relevant pharmacogenomic information in Hungarian SmPCs would reinforce implementation of pharmacogenetics. Underpinning future perspective is to support regulatory stakeholders to enhance inclusion of pharmacogenomic biomarkers into Hungarian drug labels and consequently enhance personalized medicine in Hungary.

A retrospective analysis of actionable pharmacogenetic/genomic biomarker language in FDA labels

“…Overall, there appears to be a lack of consensus between the actionable PGx biomarker in the FDA‐PGx table and the CPIC/DPWG guidelines. The lack of consensus between the FDA‐PGx and the CPIC/DPWG guidelines or the drug labels in other countries have also been reported recently 30,34,35 . One of the reasons could be due to the statistical power in clinical studies with a limited number of patients, particularly in clinical trials with patients carrying low‐frequency variants before the drug approvals.…”

“…The lack of consensus between the FDA-PGx and the CPIC/DPWG guidelines or the drug labels in other countries have also been reported recently. 30,34,35 One of the reasons could be due to the statistical power in clinical studies with a limited number of patients, particularly in clinical trials with patients carrying low-frequency variants before the drug approvals. Over the last decade with advances in F I G U R E 5 Summary of pharmacogenetic/genomic biomarker classification in the US Food and Drug Administration-pharmacogenetic/genomic (FDA-PGx) table.…”

Precision Medicine in Kidney Transplantation: Just Hype or a Realistic Hope?

“… 145 , 146 In certain fields in medicine such as oncology, due to high side-effect profile and astronomic costs of new biologic and chemotherapy medications, precision medicine is rapidly being implemented in clinical practice. 147 - 149 Despite the enormous cost of caring for transplant patients and vulnerability of these patients, transplant medicine is lagging behind in implementing precision prescribing. Therefore, in addition to potential optimization of transplant outcomes, precision medicine in kidney transplantation may be cost-effective from payer’s standpoint.…”

Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression—Arguments for Preemptive Testing

“…The labeling for some of the products includes specific actions to be taken based on the genotype. In total, 28 drug label annotations already exist for psychiatric drugs, only in the field of oncology do more drug label annotations exist [ 1 ]. In psychiatry, the evidence for adverse drug events for certain genotypes is high as the therapeutic range is narrow in many antipsychotics and antidepressants.…”