Through subsidiary Oncogene Science, Bayer Healthcare is exploring the utility of using serum, not tumor samples, to detect biomarkers associated with targeted therapies, including an existing Her2/neu test and an evolving EGFR diagnostic.
"I would say that our primary goal right now is to try to associate our serum test with Her2/neu therapies that are in development," Walter Carney, president of Oncogene Science, told Pharmacogenomics Reporter this week.
After capturing drugmakers' interest in testing patients in clinical trials for serum Her2/neu levels, Oncogene's next goal is to insinuate its Her2/neu serum test into the adjuvant setting, augmenting Herceptin treatment as a monitoring procedure.
Oncogene has had some success in having its test used in clinical trials GlaxoSmithKline is testing serum Her2/neu levels in trials of a small-molecule inhibitor of that receptor, according to Carney. But the firm has been less successful at getting the word out about using the test to monitor targeted therapies in the clinic, even though the Her2/neu test was cleared by the US Food and Drug Administration three years ago to monitor the Her2/neu levels of patients with metastatic breast cancer. Along with other clinical and diagnostic factors, the test can be used to guide therapy, but it is not cleared to determine a patientâ€™s prognoses, nor to support the prescription or monitoring of Herceptin treatment specifically.
"My problem is that a lot of people haven't heard about this."
The Her2/neu test is the predecessor of what may be a line of targeted-therapy diagnostics using the relatively novel approach of testing serum. "We have serum tests for other target therapies, but we don't know if they work yet," Carney said. These nascent tests include a diagnostic for serum EGFR, which is being investigated as a possible indicator of tumors susceptible to AstraZeneca's lung cancer drug Iressa, whose administration has been shown to alter serum EGFR levels, he added. "The tissue test [looks at] the primary tumor, but all of the drugs are tested in people with metastatic cancer, and these are really completely different studies."
Another serum test Oncogene is working on involves biomarkers related to a Bayer kidney cancer drug under development called Sorafenib, Carney said. "We know that drug works well against renal-cell carcinoma, and we probably don't need a biomarker there," but other indications, such as breast, colon, and lung cancer, will probably require biomarkers to identify patients who respond to the drug, he said.
But interest in the existing serum test is low, and it may be a harbinger of the market's response to its successors. "My problem is that a lot of people haven't heard about [the Her2/neu serum test]," Carney said, despite the fact that an ELISA test is distributed by DakoCytomation, Bayer sells an automated version, and service using Oncogene's technology is offered by reference labs including LabCorp and Specialty Laboratories.
Essentially all of the sales of Oncogene's Her2/neu serum test go through Dako, which, because it is an immunohistochemistry company, "hasn't done a terrific job of giving us a lot of exposure because serum assays are new to them," Carney said. But because Dako carries the Her2/neu IHC test, the pairing makes good business sense, he added.
At least partly motivated by the opportunity for exposure, Carney is speaking at this week's IBC Clinical Biomarkers meeting in Cambridge, Mass., about Oncogene's data and the serum test in general.
The company also plans to submit a study involving about 300 women either to the Journal of Clinical Investigation or the New England Journal of Medicine "after the first of the year," Carney said. The study demonstrates that patients having Her2/neu levels below 15 nanograms per milliliter have significantly better prognoses and survival times, he added.
Carney declined to disclose the test's market size, but speculated that it would grow.
More than 90 percent of all breast cancer patients receive an IHC Her2/neu 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, an Abbott spokesperson told Pharmacogenomics Reporter in August. Currently there are about 212,000 newly diagnosed patients eligible for a test, according to Abbott.
As an immunohistochemistry company, Dako, "hasn't done a terrific job of giving us a lot of exposure because serum assays are new to them."
Although the Her2/neu serum test is intended as a prognostic indicator capable of identifying metastatic breast cancer patients who might be in need of more aggressive therapy after tumor removal, the test's clinical utility has not yet been fully established.
"I think what this will allow physicians to do in the future is actually control Her2/neu-positive tumors by monitoring and if you can maintain a level less than 15 [nanograms/milliliter] it seems like you can keep a Her2/neu tumor in check" with adjuvant Herceptin therapy," Carney said. "I think it's the first serum test that goes with a targeted therapy."
If the diagnostic proves reliable and useful, it has the potential to increase the market for Herceptin. Between 10 and 30 percent of women with primary breast cancer continue to show elevated serum Her2/neu levels after primary tumor removal, and may still be eligible for treatment with the drug, even though Her2/neu cannot be detected with either FISH or immunohistochemistry, Carney said. As many as 60 percent of women with metastatic cancer can have a Her2-positive tumor, he said.
Since the serum test cannot be used as the basis for prescribing the drug, Oncogene has been suggesting that patients testing positive for Her2/neu following tumor removal have their original tissue sample retested, or that they undergo a biopsy for metastatic cancer along with a FISH or IHC Her2/neu test, said Carney. The company would like to continue to monitor patients receiving Her2-related drugs for their entire lives, but the test probably has no value as a cancer screen, he added.
Patients with metastatic breast cancer often have Her2/neu levels as high as 9 micrograms per milliliter, or about 600 times normal levels, said Carney. Elevated Her2/neu levels are associated in Oncogene's studies with poor response to some types of chemotherapy and with a poor response to hormone therapy, he said.
Beyond the clinical trial with Glaxo, Oncogene's Her2/neu serum test has been used to successfully monitor levels of the protein in preclinical trials with an undisclosed company, Carney said.
Chris Womack ([email protected])