US FDA norms on Clinical Pharmacogenomics may provide clear rules for new drug devpt

The US Food and Drug Administration (FDA) has now issued the guidance for Industry on Clinical Pharmacogenomics which refers to a Premarket Evaluation in Early-Phase Clinical Studies and Recommendations for labelling.

The US Food and Drug Administration (FDA) has now issued the guidance for Industry on Clinical Pharmacogenomics which refers to a Premarket Evaluation in Early-Phase Clinical Studies and Recommendations for labelling.

The guidance is intended to assist the pharmaceutical industry and other investigators engaged in new drug development in evaluating how variations in the human genome, specifically DNA sequence variants, could affect a drug’s pharmacokinetics (PK), pharmacodynamics (PD), efficacy, or safety.

The norms provide recommendations on when and how genomic information should be considered to address questions arising during drug development and regulatory review.

According to pharma companies like Biocon and Micro Labs which are engaged in new drug development efforts, a guidance will allow to strictly adhere to norms and ensure that speedy clearances are sought.

The application of Pharmacogenomics approaches during drug development is an evolving process that begins with discovery and continues through confirmation of clinical efficacy and safety outcomes. The focus of this guidance, however, is to provide advice on general principles of study design, data collection, and data analysis in early-phase trials.

The document guidance does not address trial design or statistical analysis considerations for later-phase, randomized, controlled clinical trials that are intended to draw definitive conclusions about treatment effects in a genomic subgroup (e.g., enrichment designs, adaptive enrichment designs, simultaneous hypothesis testing overall and within subgroups), or co-development of a drug and in vitro diagnostic, stated the regulatory authority.

The considerations provided are more relevant for exploratory and observational studies intended to generate genomic hypotheses that may then be tested in prospectively designed phase III trials. For instance, early-phase data on genomic-dependent dosing or efficacy, even when not definitive, can provide guidance on dosing or patient selection in later-phase trials, or inform the strategy for further collection of genetic and related biomarker data in later controlled trials, said the regulatory authority.

Genetic differences between individuals can affect virtually all aspects of a disease and its treatment, including the rate of disease occurrence. The risk of disease progression or recurrence, the drug most likely to provide benefit along with the therapeutic dose, the nature and extent of beneficial responses to treatment and the likelihood of drug toxicity are also provided.

Drug product labelling has increasingly included information obtained during drug development on the treatment effect in a subset of patients with a particular genetic/ genomic status, on altered risk - benefit balance in genetic sub-groups, or on the need to genotype to guide dosing.

Drug product labelling has also been revised after approval, based on post market experience, to include Pharmacogenomics information that can inform the benefit - risk relationship or allow dosing of the drug to be adjusted for individuals. “It is hoped that ascertainment of genomic information throughout drug development will enable earlier discovery of clinically important genomic differences,” said the regulator.

Pharmacogenomics studies can contribute to a greater understanding of inter-individual differences in the efficacy and safety of investigational drugs. This  research depends on the collection and use of biological samples to generate data.

For early assessment in early-phase clinical studies, Pharmacogenomics has to identify the populations that should receive lower or higher doses of a drug. It needs to classify responder populations based on phenotypic, receptor, or genetic characteristics. Further, it has also insisted to look for high-risk groups which report serious adverse drug reactions.

Labelling should include information on Pharmacogenomics only if it is useful to inform prescribers about the impact of drug on particular genotype where a test is required before actual drug administration.