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DxS Submitting PMA Application for Class III TheraScreen KRAS Assay

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DxS is submitting its TheraScreen KRAS test for premarket approval to the US Food and Drug Administration, according to a company official.

“We are using a modular PMA approach,” DxS Stephen Little said.

A modular PMA is a process where data on different aspects of the diagnostic, for example analytical, manufacturing, and clinical, can be submitted when they are complete rather than waiting for all modules to be available prior to submission.

According to Little, the “first module was submitted recently [and the] clinical module is still to follow.”

Last December, DxS signed an agreement with Amgen to market its KRAS assay in the US as a companion diagnostic for Amgen's colorectal cancer therapy Vectibix (panitumumab).

“FDA is on record as saying that they consider the risk profile of the companion diagnostic the same as the drug, therefore it must be appropriately controlled,” Little said. “They consider [it a] Class III" device and therefore a PMA is required.

In recently issued draft guidelines, the agency has indicated that tests making predictive claims regarding drug benefit would likely be considered a Class II or III device [see PGx Reporter 05-16-2007].

Recent studies have shown that metastatic colorectal cancer patients who carry the wild-type version of the KRAS gene are much more likely than those with the mutated form of the gene to benefit from monoclonal antibodies, such as Bristol-Myers Squibb's Erbitux (cetuximab) or Amgen’s Vectibix [see PGx Reporter 06-04-2008].

European regulators have narrowed the indication for both Vectibix and Erbitux to include treating only those patients whose tumor carries the wild-type KRAS gene. By comparison, the FDA has refused to make such a recommendation absent results from prospective clinical trials.

However, last December, the FDA's Oncologic Drugs Advisory Committee considered Vectibix and Erbitux in discussing issues surrounding the submission of retrospective study data, including assay validation, appropriate sample requisition, and biomarker discovery.

Amgen and BMS have each submitted retrospective analyses as part of applications to update their drugs' labels with gene-response data [see PGx Reporter 12-17-2008].

Although the advisory committee recommended inclusion of KRAS information in the package inserts of the two agents, the panel did not suggest specific label language or the placement of the KRAS information in the specific section of the package insert.

At a conference in San Francisco last week, Little told Pharmacogenomics Reporter sister publication GenomeWeb Daily News that the debate over prospective and retrospective studies has led to "confusion" in the industry about the utility of KRAS testing in the administration of Vectibix. The kafuffle was further complicated by the fact that DxS’ KRAS test was not co-developed simultaneously with Vectibix, he added.

Last month, both BMS and Amgen acknowledged that the lack of clear guidance from the FDA regarding KRAS testing had negatively affected the sales of their drugs [see PGx Reporter 02-04-2009].

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According to Little, once more drug/diagnostic combination products are co-developed, similar confusion can be avoided.

Going forward, DxS’ strategy will be to start speaking to potential partners about companion diagnostics when the drugs are in Phase I and Phase II studies. The goal, Little said, is to launch the diagnostic "on the same day the drug is launched."

DxS will be announcing new pharma partnerships for companion diagnostics in the coming months, he added, but did not elaborate.

According to Little, sales for the TheraScreen KRAS test have "taken off.”

Although Little would not provide exact sales figures for its KRAS test, he noted that companion diagnostics are the company’s main revenue driver. From 2007 to 2008, the company's revenues grew four-fold, and Little expects sales to double this year.

Specifically, "the adoption rate for the KRAS test has been phenomenal," he said, mainly because the "drug industry is pushing it."

DxS recently hired Jane Papadaki-Markley as its sales and marketing director for North America. The company is "about to set up US sales and support operations,” Little said. DxS currently has 70 employees worldwide, and plans to hire more in the coming months.

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