Pharmacogenomic data guidance: Industry objects to reporting exploratory studies

An industry group representing pharmaceutical and biotechnology companies is asking the US Food and Drug Administration (FDA) not to require the reporting of results from exploratory pharmacogenomic studies, saying it could disincentivize companies from performing these studies at all.

The comments, from the Industry Pharmacogenomics Working Group (I-PWG), are in response to the agency’s draft guidance on Pharmacogenomic Data Submissions, issued in March 2023. The guidance outlines the types of pharmacogenomic study findings and data that must be included for investigational new drug applications (INDs), new drug applications (NDAs) and biologics license applications (BLAs).

If finalized, the draft guidance from March 2023, would replace final guidance for industry that the agency published in 2005. (RELATED: FDA issues guidance on submission of pharmacogenomic data, Regulatory Focus 21 March 2023)

Exploratory studies

Both the I-PWG and Pfizer submitted comments to FDA saying the draft guidance would significantly increase the number of required pharmacogenomic study submissions compared to the 2005 guidance that is currently in place. Under the current guidance, most submissions of exploratory pharmacogenomic data are considered voluntary. I-PWG and Pfizer emphasized that exploratory studies often have non-validated results and are performed with the goal of generating preliminary information.

“Response to drug treatments can be highly variable and disease phenotypes can be extremely heterogeneous. Using exploratory genomic and genetic tools to understand patient variability and diseases should remain as scientific enquiries and not be a regulatory submission requirement unless the results are to be used in support of regulatory filings or be used for making clinical treatment decisions,” I-PWG wrote in public comments on the draft guidance. “In most instances, these studies are considered hypothesis generating, and require many additional studies before the results become validated and have clinical utility. Interpreting them before they have reached scientific maturity can result in spurious interpretations. The majority of these findings will not be clinically actionable or reach the threshold of clinical validity.”

I-PWG urged FDA to keep in place the current voluntary framework for reporting of exploratory pharmacogenomic studies. Additionally, the group called on FDA to provide timelines for any new requirements and not to apply any requirements retroactively to studies and analyses that have already been conducted.

As currently written, the draft guidance “would have the unintended consequence of disincentivizing companies from performing exploratory pharmacogenomic studies on clinical trial data sets,” I-PWG said.

More details needed

Boehringer Ingelheim Pharmaceuticals asked FDA to provide specific examples of the several pharmacogenomic biomarkers with “well-accepted mechanistic and clinical significance” used in drug development that the agency mentions in the draft guidance.

The American Cancer Society Cancer Action Network (ASC CAN) also asked FDA for clarity on some of the requirements in the guidance. For instance, the group asked whether the FDA was requiring sponsors to submit data, if it exists, on subgroup differences or if the agency is compelling sponsors to conduct those studies. “The difference between compelling that studies be conducted and reported versus compelling reporting whenever studies are voluntarily conducted is an important distinction. We believe the intention is to compel studies and reporting but believe the language should be clearer in that regard,” wrote ASC CAN President Lisa Lacasse.

ASC CAN supported the recommendation in the draft guidance that pharmacogenomic study findings be reported to FDA in detail as part of the IND if the findings support the use of a genomic biomarker in the design, conduct, or analysis of planned clinical trials. Additionally, the group supported the draft guidance recommendation that pharmacogenomic data be reported as subject-level data in a detailed report if it is used in drug labeling. ASC CAN suggested that sponsors should also include data on pharmacogenomic biomarkers that informed “adverse drug-gene interactions.”

Comments on draft guidance

Pharmacogenomic data guidance: Industry objects to reporting exploratory studies

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