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Respiratory Dxs Head for FDA; CombiMatrix Eyes Avian Flu Screening; Tm Targets Clinical Severity

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CombiMatrix and Tm Bioscience have both launched molecular diagnostics with the potential to guide treatment for influenza, but a test capable of directing physicians to the right drugs to combat different viral strains remains out of reach.

Both companies announced steps toward achieving regulatory clearance for their respiratory assays: CombiMatrix said it plans to file for US Food and Drug Administration clearance for its Influenza A Research Microarray test, while Tm Bioscience said that it had begun marketing its new ID-Tag RVP (Respiratory Viral Panel) test under the Investigational Device Exemption rules as it prepares to file with the agency.

In addition, CombiMatrix said last week that it will distribute its custom and pre-made chips — including the new influenza A array — through Taiwan-based Cold Spring Biotech to researchers in China, Taiwan, and Hong Kong. The deal follows a similar December distribution agreement with Singapore-based Cell Sciences, which gave the company access to Singapore, Malaysia, Thailand, the Philippines, Hong Kong, and Indonesia. In its statements announcing each of the deals, CombiMatrix highlighted the region's growing genetic research capacity, noting that the influenza A microarrays could potentially play a prominent role in avian influenza research conducted there.


"We build this not to specifically address the avian flu pandemic, but to say, 'What do you need to do in a hospital where you've got patient-management regimes and you've got infection controls in hospitals that you need to manage, and you have the broader picture of the community health?'"

How much the recent deal expands the market for CombiMatrix's microarrays "is hard to determine, exactly," company spokesperson Bret Undem told Pharmacogenomics Reporter. "It's definitely a growing area, but I couldn't put a number on it," he said. Nevertehless, greater China "could be the big chip market" for influenza microarrays, he said.

CombiMatrix will only begin specializing its respiratory microarrays to sub-type virus strains, such as Tamiflu-resistant flu, "once the chip is in bigger use, and that's what we're trying to achieve with this distribution, as well as our own efforts within the [United States], talking with the different agencies," said Bret Undem, CombiMatrix vice president, in an interview this week.

Undem characterized the general market for avian influenza diagnostics as small, partly because "there hasn't been a huge outbreak yet," although it is growing through poultry surveillance and epidemiological screening and monitoring. "We're kind of at the beginning of it."

The company's subsidiary, CombiMatrix Molecular Diagnostics, expects CLIA approval for its facility in Irvine, Calif., to be awarded "shortly," Undem said. The CMD lab plans to offer an influenza typing and detection diagnostic service using the influenza chip, and "once we get some experience and usage, then we'll file for FDA approval on it," said Undem. Cold Spring Biotech will not offer CMD services under the recent deal, although "that could evolve under another agreement," he added.

Amit Kumar, the company's CEO, told Pharmacogenomics Reporter in November that the firm planned to file its influenza chip for FDA clearance in late 2005 or early this year. "Filing for FDA approval is something that we plan to do for the influenza chip in general, which will include H5N1 [probes]. Now, if one of these [strains] gets out of hand, it's not clear whether FDA is going to accelerate approval processes" for that particular strain, he said.

Undem confirmed CombiMatrix' plan to file early this year. The diagnostic product will be a general influenza strain-typing diagnostic, although it might become more specialized, he said.

CombiMatrix' distributors have discussed the influenza chip's use in screening and monitoring of avian flu with several East Asian government officials, said David Danley, the director of the firm's homeland security and defense programs. He declined to name the governments.

The company is also working on an overlapping project under contract with the Air Force that CombiMatrix announced in September. The project will be conducted in two parts — the first chip to result will use many of the same probes as the company's influenza chip, and will add serious, common pathogens, such as parainfluenza, adenovirus, and pneumoniae, said Danley. A second phase will add pathogens that are either less common or less dangerous, such as rhinovirus, biothreat agents, and a variety of respiratory pathogens, he said.

The influenza chip is currently capable of distinguishing between "all of the different kinds of influenza those birds are carrying," as well as human flu viruses, Danley said. As far as using the chip for guiding treatment, "it seems like you can distinguish between viruses that are more pathogenic in humans, but that is not proven," while the company does not have the data or samples to detect viral drug resistances, he said.

Like other companies with flu-strain typing assays, CombiMatrix is focusing on identifying the pathogenicity of an influenza strain by typing its hemagglutin-gene region, in which drug resistance may not reside, said Danley. The hemagglutin protein is largely responsible for the virus' binding affinity.

Should the company decide to create specialized chips for identifying drug resistance, "we can create and start producing a chip within a matter of four to five weeks" after receiving gene sequences in which drug resistances are known to reside, said Danley.

Tm Biosciences' Flu Entry

Tm Biosciences is a little late introducing its test based on its own timetable. The company said in a November statement that it planned to have its influenza test ready for hospital laboratories and reference laboratories by early December. Its ID-Tag respiratory virus panel, which became available last week for research use under an FDA Investigational Device Exemption, is intended to distinguish between 21 respiratory viruses, including respiratory syncitial virus, SARS, parainfluenza, and various influenza viruses.

The firm plans to sell the test "worldwide, including in Asia" and it is "in discussions" with potential distributors in East Asia, said Richard Janeczko, chief scientific officer at Tm. He declined to be more specific.

Instead, Tm appears to be more focused on the test's medical applications. "We're just getting the final approval on the clinical protocol, and we will be filing that [for in vitro device clearance with the FDA] fairly soon," he said. He declined to be more specific. "We build this not to specifically address the avian flu pandemic, but to say, 'What do you need to do in a hospital where you've got patient-management regimes and you've got infection controls in hospitals that you need to manage, and you have the broader picture of the community health?'"

Although the company said in November that it may update the test to differentiate drug-resistant strains or human-transmissible strains of viruses, that possibility seems distant. Tm Bioscience does not have drug-resistance sub-typing in its assay right now, said Janeczko. "I really don't have a plan to add that unless there's some compelling reason to do it. I think far more interesting would be to improve the assay by giving a really rapid point-of-care kind of application, but we haven't started that yet," he said.

Tm Biosciences had discussions about drug resistance sub-typing "early on," but the company was not planning on building a pharmacogenomic test, particularly since Tamiflu is not a very effective treatment, even when used against sensitive strains, said Janeczko.

The assay also cannot, at present, distinguish avian flu viruses that are more capable of human-to-human transmission, Janeczko said. "Even if it was that version, it wouldn't change the course of action from a clinical or a public-health point of view," he said, because the detection of H5-containing flu viruses in humans triggers quarantine procedures, the immediate administration of antiviral drugs, as well as other serious measures.

Should the company decide to delve into either of these realms of flu sub-typing, it can develop a new test as quickly as three to five months, Janeczko said. "Version two is still on the drawing board," he added.

Tm Bioscience's competitors' "level of H sub-typing is not the same as ours," said Janeczko. "That's the key thing for public health surveillance labs that are working under the [World Health Organization] or Pan-Asian Health Organization, or any of the National Influenza Centers — it's the one thing that they need."

"The key thing is to know, 'Have I got an influenza A?' and the most common, likely outcome[s] in the United States are H3 and H1 right now," said Janeczko.

— Chris Womack ([email protected])

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