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A New Test Tries to Muscle in on Established Players As Her2-Diagnostic Market Matures

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Is it getting crowded in here?

In a bid to grab a share of a market dominated by two diagnostic players, BioGenex has been cleared by the US Food and Drug Administration to sell its monoclonal antibody kit for identifying responders to Herceptin.

The kit, called InSite Her2/neu, features a technical advantage over DakoCytomation’s polyclonal HercepTest — the market leader — and a practical advantage over the monoclonal Her2/neu antibody made by Ventana Medical Systems.

“Antibody to antibody, the major advantage of having a monoclonal over a polyclonal is the specificity,” said Promila Rastogi, product manager for reagents at San Ramon, Calif.-based BioGenex.

But will the test win over reference labs?

The market for Her2/neu tests in the United States is not particularly large — Rastogi reckons it’s “at least” $5 million. BioGenex’s rivals in this space — the two existing Her2/neu antibody-based products as well as the Her2/neu in situ hybridization test sold by Abbott Laboratories — are cleared by the FDA.

The FDA notified BioGenex in a letter dated Dec. 22 that it had cleared the InSite Her2/neu kit in both manual and automated formats, and the company announced the news this week. The product will be launched at the United States and Canadian Academy of Pathology meeting in San Antonio in February, said Rastogi.

The kit is “priced competitively” with Dako’s product, but Rastogi declined to say exactly how much it will cost. Compared to Ventana’s her2 antibody, InSite comes in “lower than them, list-price wise,” she said. In its application for clearance from the FDA, BioGenex’s tests only sought concordance, “and there was excellent concordance,” she added.

But there’s more to this market than price points. “The elephant in the kitchen here is that … the FISH test by Abbott is now widely regarded to be even more sensitive and specific for assessing true Her2 status than any immunohistochemical assay,” said Andrew Seidman, associate attending physician for the Breast Cancer Medicine Service at Memorial Sloan Kettering Cancer Center.

Antibody-based tests currently benefit from the ability among many laboratories to perform IHC tests “more readily” than ISH procedures. But these labs usually use ISH to clarify marginal results, Seidman said.

“My guess would be that immunohistochemistry is still the dominant test,” by the number of users, with Dako at the top, said Seidman.

In their own experiments at Memorial Sloan Kettering, Seidman and colleagues saw potential cross-reactivity using polyclonal antibodies when they compared the ability of monoclonal and polyclonal Her2 antibodies to assess a response to Taxol and Herceptin. “Often we get a higher rate of Her2 positivity with the HercepTest than we would expect,” he said. “When we look at monoclonal rates of Her2 positivity, it more closely reflects what we see when we go FISHing.”

Nevertheless, “many docs have actually abandoned immunohistochemistry and [have] now gone directly to FISHing for Her2,” said Seidman. Formalin-fixed paraffin-embedded tissue samples show a loss of tumor antigenicity that can lead to false-negative results using IHC, while antigen-retrieval techniques can induce false-positive results — two pitfalls that ISH tests can mostly avoid, he added.

Because of this, the National Comprehensive Cancer Network, in May 2003, revised its Practice Guidelines in Oncology to note that ISH Her2 testing may be more accurate than IHC.

But it won’t be over for immunohistochemistry for quite a while, especially if BioGenex is able to spread the word about InSite’s advantages. The kit could have an edge over polyclonal antibodies and InSite’s staining reagents, which are included in the kit, may help in a comparison with Ventana’s her2/neu antibody. “We’ve compared Dako and Ventana — a polyclonal versus a monoclonal,” said Ann Demarest, a technologist in the molecular pathology department at Legacy Emmanuel Hospital in Portland, Ore. “The monoclonal is, of course, more specific, but in the one we evaluated, [it was] much more difficult and subjective to read.” She was unable to say whether different staining reagents would have improved the situation.

In trying to break into the Her2 market, BioGenex will have to overcome significant inertia favoring Dako. “Most of our customers use HercepTest on our instruments,” and both the customer and Dako have validated it, said Dako spokesperson Gitte Sjorslev in an e-mail exchange with Pharmacogenomics Reporter. “Also the lab technicians have received training in using the kit properly, so I think it would be quite a decision to change to another supplier,” she said.

The FDA cleared BioGenex’s InSite diagnostic for manual use and for use with the company’s two automated staining systems — the i6000 system and its OptiMax-Plus system. Dako supports manual use of HercepTest, and automated staining using its Autostainer and Autostainer+.

Despite the monoclonal antibody’s “hands down” superiority to polyclonal Her2 testing, the pathology department at Legacy Emmanuel is not rushing to change the way things are done, said Demarest. “As far as false positives with the polyclonal that we’re using, our numbers fit, pretty much, [a] community standard,” she said. “I don’t think that we’re looking to change anytime soon.”

Legacy Emmanuel uses polyclonal antibody tests up front, following with ISH to decide indeterminate experiments, said Demarest. “There’s a lot of stuff out there and it’s just too expensive to validate everything that comes out.”

— CW

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