This article has been updated from a previous version to clarify statements from a TrimGen official about the company's expectations regarding FDA approval for its test. The company said that it has not yet received official notification from the FDA, and that it expects the test to clear in the near future, rather than by the end of the month, as the firm previously stated.
TrimGen expects the US Food and Drug Administration to clear as an in vitro diagnostic its warfarin-dosing test “in the near future,” James Doherty, TrimGen product specialist, told Pharmacogenomics Reporter this week.
Maryland-based TrimGen, which submitted its 510(k) application for the eQ-PCR LightCycler Warfarin Genotyping Kit in December 2007, said it plans to differentiate its test from rivals’ products based on its 1.5-hour turn-around and relative ease of use.
TrimGen has looked at the clinical and analytical validity of the test in a 170-patient-sample study at three sites — Virginia Commonwealth University, Oregon Health University, and TrimGen Laboratories — where approximately 2,900 tests were performed. Doherty said the diagnostic, which is based on Roche's eQ-PCR LightCycler platform, had 100-percent agreement with bi-directional sequencing.
TrimGen also markets the Mutector II Warfarin Genotyping Test kit, which analyzes samples using an ABI capillary sequencer.
If cleared, the company’s LightCycler warfarin test will be the fifth such product to win regulatory approval in the US, behind those made by ParagonDx, AutoGenomics, Nanosphere, and Osmetech. There are also several homebrew assays marketed by Laboratory Corporation of America, Idaho Technology, and Clinical Data, among others.
TrimGen’s test is designed to detect what are generally believed to be the most clinically relevant genetic variations responsible for patient sensitivity to the anticoagulant: the CYP 2C9*2 (C430T), 2C9*3 (A1075C), and VKORC1 (-1639 G>A) mutations.
TrimGen plans to differentiate its test from competitors based on the fast turn-around time and ease of use of its product.
However, there are several competing products out on the market that offer testing for other mutations. For instance, Genelex’s homebrew Warfarin Target Dose Safety Test, based on Tm BioSciences’ Tag-It Universal Array platform, gauges CYP 2C9 *2, *3, *4, *5, *6, and VKORC1 (-1639 G>A) mutations. Nanosphere’s FDA-approved Warfarin Metabolism Nucleic Acid Test gauges CYP 2C9 *2, *3, as well as VKORC1 (-1639 G>A) and (1173C>T).
Meanwhile, AutoGenomics boasts that its INFINITI assay detects 15 2C9 and VKORC1 variants, more than any other company in the market. Among the 15 variants the INFINITI assay detects, several polymorphisms will be specific to particular ethnicities – such as the *4 variant identified exclusively among Japanese people and the 8773 SNPs in VKORC1 found in 21 percent of African Americans [see PGx Reporter 10-10-2007].
And although TrimGen is touting a run time of 1.5 hours for its test, there is competition on this front as well, since ParagonDx's Rapid Genotyping Assay claims to complete the process in less than 30 minutes and Nanosphere's Verigene System takes 1.5 hours. In comparison, AutoGenomics' Infiniti Warfarin XP assay requires 10.6 hours. Third Wave's 96-well platform and Luminex's Tag-It assay, which are not FDA cleared, report run times of around three hours.
Ultimately, price stands to be one of the most important differentiating points, particularly since questions of clinical utility have kept major insurers from reimbursing gene-based warfarin-dosing tests [see PGx Reporter 12-19-2007].
Currently marketed warfarin sensitivity tests range in price between $200 and $500 for each patient. TrimGen's assay has a list price of $960 for 16 patients.
“The kit list price is $960 and has reagents for 16 patient samples, which works out to be $60 per patient sample,” Doherty said. “What the laboratory charges beyond that is up to them.”
According to TrimGen’s Doherty, reimbursement discussion will be initiated by the laboratories using its kit. “Once we attain 510(k), assuming the lab doing the test is CLIA certified, they should already have a protocol in place for negotiating reimbursement schedules,” Doherty said.