Pharmaceutical Companies Seek Clarity On Evidence Needed For Drug Label Change

Main Category: Pharma Industry / Biotech Industry
Also Included In: Regulatory Affairs / Drug Approvals
Article Date: 05 Jan 2009 - 1:00 PST

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With the discovery of a growing number of predictive biomarkers for existing drugs, the question of when and how to add pharmacogenetic information to drug labels has taken on greater urgency. On December 16 the Oncologic Drug Advisory Committee (ODAC) of the Food and Drug Administration (FDA) met in Gaithersburg, MD with representatives from pharmaceutical companies Amgen and Imclone. The committee and the company representatives discussed what types of studies need to be done before existing drug labels can be amended with new biomarker information. Amgen and Imclone presented data on the effect of variants in the K-RAS gene on the efficacy of Vectibix and Eribitux, drugs used to treat colorectal cancers. They seek a label change that recommends drug usage based on predictive genetic subgroups.

FDA has stated clearly that the best way to show correlation is by developing drugs in parallel with biomarker diagnostics through prospective studies. However, genetic associations with response to a drug often emerge after the drug is already in use. In addition, in the case of Vectibix and Eribitux, there are serious ethical issues in prospectively recruiting patients with K-RAS mutations into a study for a drug that is likely to be ineffective. In briefing documents for the meeting, FDA had proposed the following requirements for retrospective device-drug co-development: well-controlled studies with sufficient sample size and biological sample acquisition for >90 percent of subjects, an assay validated by FDA, analysis by individuals blinded to the outcome results, and prior FDA review of and agreement to the analytic plan for testing the hypothesis.

The companies presented data from six retrospective studies, which showed that certain somatic mutations within the K-RAS gene render the cancer drugs ineffective. The studies on K-RAS had limitations. For example, they were performed after drug development; they used archived samples that were available for only a portion of the total subject population, and therefore possibly biased; and the K-RAS analysis was performed with an assay not yet validated by FDA. ODAC will review the FDA criteria for retrospective biomarker-drug interaction studies in light of the data presented at Tuesday's meeting. ODAC's consensus could help urge the FDA to update the labels of Vectibix and Eribitux to include K-RAS analysis as a prerequisite for usage. Written by - Stephanie Devaney

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The Genetics and Public Policy Center Johns Hopkins University
http://www.dnapolicy.org