The European Medicines Agency (EMA) has put out for consultation a reflection paper on the use of pharmacogenomic biomarkers as patient selection and treatment stratification tools in drug development.

A draft of the reflection paper was agreed by the Pharmacogenomics Working Party of the EMA’s Committee for Medicinal Products for Human Use (CPMP) in March and adopted by the CHMP for release on 9 June. The deadline for comments is 25 November 2011.

The reflection paper on methodological issues associated with pharmacogenomic biomarkers in relation to clinical development and patient selection discusses the role these markers can play in predicting which patients are likely to benefit from a particular medicine or which may be susceptible to side-effects.

It reflects the experience gained by the EMA through applications for marketing authorisations and scientific advice, the agency notes.

GBM boom

The availability of techniques facilitating the study of the human genome has led to an “exponential increase” in research into genomic biomarkers (GBMs) for disease diagnosis, as markers of either prognosis or response to treatment, the reflection paper points out.

Theoretically, it adds, GBMs should offer “the advantage of improved specificity and reduction of heterogeneity that is an integral part of phenotypic population grouping”.

This characteristic is seen as highly attractive in drug development, given the potential for GBMs to reduce attrition and development costs through improved understanding of mechanisms of action, better awareness of potential adverse events, and use of novel development strategies in preclinical and clinical trials.

Wide applications

GBMs may have a wide range of applications in clinical drug development, the paper notes.

These include patient selection; prognoses; stratification of patient groups or treatment strategies; early evaluation of treatment effects, including adverse reactions; pre-defined sub-group analyses; and enabling novel trial designs that “might not be possible otherwise due to heterogeneity of clinical characteristics”.

GBMs could also play a valuable role in risk management strategies, including risk minimisation by aiding a priori identification of patients susceptible to severe adverse effects, the paper says.

Regulatory lag

While a number of these issues have been discussed extensively in the literature over recent years, “specific aspects relating to drug development and discussion on regulatory considerations have lagged behind”, the EMA comments.

The aim of the reflection paper is therefore “to provide an evidence based consideration of GBM-related issues from a regulatory viewpoint”, while also touching on the co-development of GBM diagnostic tests for use with medicinal products.

A full version of the paper may be accessed online through the EMA’s website at