In a recently announced three-year collaboration, AutoGenomics and Targeted Molecular Diagnostics will work together to develop microarrays that meet the needs of drug makers and researchers developing therapeutics affecting the Her1 and Her2 pathways, such as Tarceva, Iressa, and Herceptin.
The first such array will measure RNA expression, and later arrays will look for mutations in EGFR and c-kit genes, among others. The arrays will run on AutoGenomics' Infiniti microarray platform. "We'll have about 10 or 12 genes on it that are …downstream of the Her1 or Her2 receptor, all the way down, and we'll be looking at ligand expression as well, for Heregulin and Her-3 and so on," said Christopher Ung, TMD vice president of business development and marketing. The assays will include "all the factors that we know, based on our work and the literature, that affect the Her1/Her2 pathway."
Receptor gene-copy number and receptor-protein expression are more commonly associated with response to drugs like Herceptin and Tarceva, and they are usually tested using FISH and immunohistochemistry, respectively. Asked why the companies were focusing on RNA expression instead, Ung said, "I think there are some academic studies out there [relating RNA expression to response] that are not well known, but I think the question of how valid these studies are has always been [asked]."
"We understand a lot about how these drugs work, and therefore we're developing this diagnostic chip because it's sorely needed out there."
Also, RNA expression is a factor that many microarrays have been built to test, while gene-copy number and protein expression are not.
While there are several genes that affect response to drugs like Herceptin and Tarceva, the collaboration marks the first time the market for Her-pathway arrays has been addressed. The list of relevant genes is constantly changing, but should TMD and AutoGenomics eventually settle on a few, the device may become a clinical molecular diagnostic supporting cancer treatment. If the results are good enough, the companies may also submit an array for US Food and Drug Administration clearance.
But TMD is not yet comfortable speaking about its plans for FDA clearance. First the companies plan to test the arrays at TMD's Chicago laboratory, evaluating their performance with cell-line material and frozen tissue, and correlating results with those produced by FISH and immunohistochemistry, said Ung. "Once we understand the performance of these chips, then we will begin putting a plan together for FDA approval," he said.
"Clinical diagnostics is the ultimate goal," said Ung. "It's one of the reasons that we chose AutoGenomics, because all of the other platforms are not really geared for the clinic — there would be serious adoption issues, whereas the AutoGenomics platform really has the clinic in mind," he said. Ung cited the platform's automation, cheaper arrays, and data-handling capabilities as factors that will grease the skids to clinical adoption.
"Based upon some numbers I heard from Roche [concerning the AmpliChip CYP450], we will definitely be less expensive than that, but as of now, we haven't established our price," said Richard Hamill, AutoGenomics COO.
In the short term, Ung said that TMD plans to use the arrays for a testing service that it will offer through its Good Laboratory Practices-compliant lab. But the companies will also sell the platform to pharmaceutical companies that want to use it for exploratory research, he said.
Despite claiming first-mover status in the Her-pathway array market, TMD and AutoGenomics are not the only companies with this market segment in mind. "That is definitely something we're looking at," Don Braakman, an Abbott Diagnostics spokesperson, told Pharmacogenomics Reporter. The number-two diagnostics company has a "broad number of probes" that might be appropriate for such an assay, but it has no specific plans to develop one, he said. Any array-based diagnostic that the company would make in the Her1/2 area would be for research use only, initially, he said.
The market for molecular diagnostics supporting Her1/2 research is not easy to estimate, and there are no arrays on the market with similar indications. However, the diagnostic companions to Herceptin, such as DakoCytomation's Hercept-test and Abbott's PathVysion FISH test, may serve as baseline estimations of the market that these microarrays could encounter in Her1/2 clinical diagnostics. More than 90 percent of all breast cancer patients receive an IHC Her2 test, and about 42 percent of those receive a PathVysion FISH test, according to figures supplied by Abbott. The number of patients receiving a FISH test likely includes patients who received it as a retest, said an Abbott spokesperson. Currently there are about 212,000 newly diagnosed patients eligible for a test, according to Abbott.
If a diagnostic becomes commonplace for patients being treated with Tarceva or Iressa, then the markets for those drugs provide some insight into the potential market for that diagnostic. No diagnostic is necessary for the prescription of Tarceva for its current indications, and it is not clear whether a diagnostic will be necessary for it to achieve first-line approval from the FDA. It also remains unclear whether a diagnostic that identifies responders can bring Iressa back to the market.
There are about 69,000 patients receiving first-line therapy for non-small cell lung cancer, and about 41,000 receiving second- or third-line treatment for the disease, said Colleen Wilson, Genentech associate director of product communications, in an e-mail exchange with Pharmacogenomics Reporter. Tarceva is approved for second- and third-line treatment of NSCLC, as was Iressa before the FDA ordered AstraZeneca to withdraw the drug from the market.
Targeted Molecular Diagnostics will first approach companies it works with in the Her1/2 or kinase-inhibitor areas, including Imclone, GlaxoSmithKline, and AstraZeneca, Ung said. The company has a lot of experience working with these drugs, "and therefore we're developing this diagnostic chip because it's sorely needed out there," he said.
AutoGenomics and TMD should have a prototype array ready for clinical evaluation in nine to 12 months, Ung said.
— Chris Womack ([email protected])