By Ben Butkus
Early-stage clinical diagnostics company Rheonix and the Mayo Clinic said this week that they are collaborating to evaluate the performance of a genotyping test for warfarin sensitivity in clinical and research settings.
The eventual goal of the partnership would be to port the validated assay onto Rheonix's "chemistry and reagent device," or CARD, a fully automated, modular molecular testing platform that is still under development but may reduce the complexity and cost of warfarin sensitivity testing, Rheonix's CEO said this week.
However, the warfarin sensitivity test won't be moved to the CARD system until the platform receives US Food and Drug Administration approval. To that end, Rheonix expects to begin clinical trials for a CARD-based version of the test at Mayo Clinic and other sites later this year in support of a 510(k) application, the company said.
"The Mayo Clinic has been granted non-exclusive access to some internally developed know-how [and to] multiple pieces of intellectual property that Rheonix has licensed from the University of North Carolina [to perform] a genotyping test for warfarin sensitivity," Rheonix President Tony Eisenhut told PCR Insider this week.
"Separately and independently, Rheonix has developed a warfarin sensitivity assay around the licensed University of North Carolina intellectual property and internally developed intellectual property," Eisenhut added. This assay, he said, is being developed on the CARD platform, and "once approved by the FDA … would allow the Mayo Clinic to offer the Rheonix assay on our CARD platform."
Rheonix did not specify the nature of the intellectual property it has licensed from UNC; however, the school owns several patent applications and awarded patents related to correlation of SNPs in the vitamin K epoxide reductase, or VKOR, gene and altered sensitivity to warfarin dosing.
The licensing agreement with Rheonix enables the Mayo Clinic to offer a laboratory-developed genotyping test for warfarin sensitivity to all of its patients. Additionally, the test will be offered through Mayo Clinic's reference laboratory, Mayo Medical Laboratories, to clients throughout the world.
In an e-mail, a Mayo Clinic spokesperson further explained that its agreement with Rheonix "involves limited rights to perform the CYP2C9 test, which is useful as one factor in determining if a patient is a poor metabolizer of warfarin. A small percentage of the Caucasian population and a slightly larger percentage of the Asian population have an alteration in the CYP2C9 and/or the VKORC1 genes that make them poor metabolizers or overly sensitive to warfarin."
The spokesperson added that Mayo Clinic is "participating in an evaluation of the Rheonix equipment and a diagnostic kit for warfarin sensitivity. We believe in the value of some genetic tests to determine warfarin response, and already perform this testing at Mayo Clinic. We chose to work with Rheonix on the evaluation of their platform and kit because the platform may allow for efficient development of several additional related warfarin tests and because we wanted the opportunity to evaluate their existing kits as a possible replacement for some of our internally developed tests."
Rheonix's CARD system integrates sample preparation, nucleic acid amplification, and endpoint detection all on a single microfluidics-based, point-of-care polymeric module a few inches thick and with an approximate footprint the size of a credit card.
Each step, or "module," in the molecular testing workflow can be swapped out of the system for an alternative method or assay technology, depending on what works best for a particular molecular test.
"For example, on sample prep, we're able to do a number of different chemistries [or] enzymatic reactions," Eisenhut said. "On the extraction side we're able to incorporate … magnetic bead purification, or more of a [silica gel-membrane] purification methodology. We've done both traditional PCR as well as [nucleic acid sequence-based amplification]. And on endpoint detection, [there's] reverse dot blot, or a low-density array, which is what we're doing right now; or fluorescence. We're able to use different endpoint detection modalities and interface it on CARD."
Last April, when Rheonix announced the completion of a $12.6 million Series A financing, it also said that it was developing several in vitro diagnostic assays for CARD, including tests for warfarin sensitivity, HPV, HIV, and sepsis. At the time, Eisenhut also said that the company anticipated filing a 510(k) application for the warfarin test before the end of 2010, a prediction he reiterated in August following the release of initial test data at the American Association for Clinical Chemistry meeting in Anaheim, Calif. (PCR Insider, 8/5/10).
However, Eisenhut said this week that the planned timeline has been pushed back, "mostly due to internal development and resource allocation than anything else." For instance, the company has begun developing sepsis testing and KRAS genotyping assays on the CARD system; "and we have a platform where we're looking to take tissue samples and be able to insert them directly onto the CARD, whether it's fresh biopsy or [formalin-fixed paraffin-embedded] tissue samples," Eisenhut said. "We've done proof of concept on both sample types on our platform."
Nevertheless, Rheonix is back on track with the CARD-based warfarin sensitivity assay, and has established a new internal timeline that involves beginning clinical trials later this year. "Three clinical trial sites have been selected, including the Mayo Clinic in Rochester, Minn.; Strong Memorial Hospital in Rochester, NY; and the Catholic Hospital System in Buffalo, NY," Eisenhut said. "We have been working with FDA to refine our test and assure that our clinical study protocol will meet their requirements and achieve a timely FDA clearance of the product."
Assuming that goes well, "hopefully in 2012, [Mayo] will be able to port its molecular assay onto our platform," he added.
Numerous other molecular tests for warfarin dosing sensitivity are either commercialized or in development. However, Rheonix believes that a molecular test on the CARD system will distinguish itself from the crowd primarily through ease of use and reduced cost.
"It's going to be push-button operation; and … bottom line, our platform is… very cost effective," Eisenhut said. "Ultimately I don't know what the final price will be. We're not there, yet. But we know that it is [under] $20 for that assay. From what we understand, it's probably less than half the cost of current solutions."
Have topics you'd like to see covered in PCR Insider? Contact the editor at bbutkus [at] genomeweb [.] com.