Pharmacogenomics in Early-Phase Clinical Development

Abstract

Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs.

KEYWORDS::

• clinical research
• drug development
• early-phase
• PD
• PGt
• PGx
• pharmacodynamics
• pharmacogenetics
• pharmacogenomics
• pharmacokinetics
• PK
• POC
• proof-of-concept

Acknowledgements

The authors would like to thank J Sundy and D Voora for their review and valuable comments made to the manuscript.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

PGx: Pharmacogenomics.

MAD: Multiple ascending dose; PGx: Pharmacogenomics; POC: Proof-of-concept; SAD: Single ascending dose.

PGx: Pharmacogenomics.