A US Food and Drug Administration advisory panel recently recommended re-labeling the breast cancer drug tamoxifen to suggest using array-based and other diagnostics to predict drug metabolism, and a trio of companies want a piece of the action if the FDA winds up taking the step.
Affymetrix, Autogenomics, and Gentris have each mentioned the panel’s findings since they were released in late October, and are making known their intentions to profit from its advice.
According to an FDA summary, its Pharmaceutical Science subcommittee met Oct. 18 to discuss changing tamoxifen’s label to include recommendations for testing patients for the drug-metabolizing enzyme CYP2D6.
The subcommittee found that the label should be updated to include information about increased risk for breast cancer recurrence in patients who are CYP2D6-poor metabolisers.
The FDA has not yet made a decision, though it usually sides with its panels.
However, the panel was split on whether the new label should recommend testing patients for 2D6 or whether the decision to test should be left to health care providers and patients.
Despite these uncertainties, Affymetrix hinted at profits by linking the 2D6 mutation the FDA panel was considering with the content of the AmpliChip, which Affy makes for Roche.
“Studies have suggested tamoxifen is not as effective in breast cancer patients carrying a specific version of cytochrome P450 2D6,” Fodor said during a conference call to discuss third quarter earnings. “This decision directly links to the availability of the AmpliChip system produced by Affymetrix for Roche. The AmpliChip system is the only FDA-cleared assay for the detection of cytochrome P2D6 variance,” he said (see BAN 11/7/2006).
The AmpliChip, which has been on the market for a little more than one year as an in vitro diagnostic, is not selling as well as Roche had initially predicted (see PGx Reporter 9/6/2006). It’s also not the only shop that stands to benefit from a new tamoxifen label: “The FDA recommendations will affect all 2D6 testing, not just AmpliChip,” Paul Billings, vice-president and national director of genetics and genomics at AmpliChip provider Lab Corp, told BioArray News last week (see BAN 11/7/2006).
Eager to cash in on that fact, Autogenomics, a Carlsbad, Calif.-based array company, told BioArray News this week it plans to submit a CYP450 2D6 panel with its BioFilmChip platform to the FDA for 510(k) clearance.
According to Ram Vairavan, Autogenomics’ vice president of sales and marketing, the company is interested in submitting the assay “because of the FDA subcommittee ruling that 2D6 is an important subparameter to assess in tamoxifen therapy.”
“We already have a comprehensive panel of alleles in our cytochrome P450 2D6, and this will become ideal for use if such a re-labeling were to occur for tamoxifen,” Vairavan said. He added that Autogenomics is “confident that that re-labeling will occur.”
“We are staying tuned in the same way we were when the subcommittee recommended the re-labeling of 2C9 and BKRC1 for warfarin sensitivity” this year, Vairavan said. “We believe this is a great revenue opportunity for Autogenomics.”
“Without an FDA mandate for testing there is no assurance of a marketplace for pharmacogenomic testing.”
Similarly, Gentris, a Research Triangle Park, NC-based pharmacogenomics firm, announced last month that it has submitted six human genomic DNA reference controls for cytochrome P450 2D6 mutation tests to the FDA for 510(k) clearance and expects it will receive approval within 90 days.
The controls are intended to be used with tests like the AmpliChip, as well as non-array based 2D6 tests like those sold by Tm Bioscience and Third Wave Technologies.
“It’s obvious that these controls have a direct usage with an FDA-approved 2D6 test, which is the Roche AmpliChip,” Gentris CEO Michael Murphy told BioArray News this week.
Murphy added that the possible re-labeling of tamoxifen could reinforce the position of pharmacogenomics companies in the marketplace. “The industry now is very much in a situation where we have to follow what the FDA does,” Murphy said. “Without an FDA mandate for testing there is no assurance of a marketplace for pharmacogenomic testing. It’s still not being offered by doctors voluntarily even though there are significant adverse drug reactions occurring that can be prevented,” he said.
A Recommendation With No Teeth?
A challenge hanging over the array industry is if the FDA re-labels tamoxifen but makes 2D6 testing an option — which would take some of the weight out of any re-labeling.
According to Felix Freuh, associate director for genomics at the FDA, there is a “very subtle difference” between a label that recommends testing and one that makes it just optional.
“We have labels that do not ‘recommend’ a test, yet put the reason for testing in fairly plain language,” Frueh told BioArray News’ sister publication Pharmacogenomics Reporter this week. “In other words, how a label will read at the end is a product of the negotiation between FDA and sponsor, and, of course, the scientific evidence that we believe needs to be addressed.”
He said that if the FDA decides to re-label tamoxifen and allows physicians to interpret testing for 2D6, it could be “less clear.”
“I would argue that it makes little sense to go through all this effort and at the end not recommend that a test would, in fact, be a good idea,” Frueh said.