In a small retrospective study, Applied Genomics has shown that its breast cancer prognostic assay accurately predicts the recurrence of estrogen-receptor positive, node-negative breast cancer.
Applied Genomics said it can get a prognostic test on the market soon than some competitors, and the company's system might prove to have an advantage in reimbursement. Applied Genomics' assay, like those of its competitors Genomic Health and Veridex, runs on a simpler platform than the microarray used to identify its biomarkers. But instead of using PCR technology, the company has taken it a step further, to immunodiagnostics, which are simpler and more familiar to pathologists than genetic and genomic tests.
In terms of how far along the company's product development is, Rob Seitz, the company's CEO, said Applied Genomics expects to launch its product in late 2006 or early 2007 once it gets access to clinical samples, as Genomic Health did with Oncotype. "I can tell you we're well ahead of [breast cancer prognostic rival] Epigenomics and where they stand on this subject," he said.
The study, which appears in this week's issue of the Journal of Clinical Oncology, involved two cohorts of 299 and 344 patients. The study showed that the company's detection panel of five antibodies (p53, NDRG1, CEACAM5, SLC7A5, and HTF9C) distinguished patients with poor outcomes from patients with good or moderate outcomes with a hazard ratio of 2.21 in validation cohort 1 and 1.88 in cohort 2. Both values were statistically significant.
Though the results don't prove that Applied Genomics' antibody-based assay can be used to identify patients who might do well on chemotherapy, "We're doing the work to show that the patients we call 'bad' [outcome] are likely to benefit from chemo," said Seitz.
In doing so, the company will be directly competing with the front-runner in the market for estrogen-receptor positive, node-negative breast cancer prognostics:. Genomic Health's Oncotype Dx. Genomic Health began a large prospective trial in late May to determine whether its test can identify patients who will respond to chemotherapy.
The advantage of immunodiagnostics is straightforward. "We expect it will be easier to reimburse; we feel it is definitely going to be easier for underserved areas" since it uses timeworn immunohistochemical laboratory techniques, said Seitz. The test will "absolutely" be cheaper than any of its nucleic-acid based test competitors, he added.
Applied Genomics will probably not have to seek reimbursement by conferring closely with payors the way Genomic Health has because its test will use established technology, and it will commercialize the test after FDA clearance. As a result, Applied Genomics will not have to seek new CPT codes from the American Medical Association — "docs could just check the existing CPT codes," Doug Ross, the company's CSO said in a February interview.
However, "there is no precedent for a five-antibody test that is billed as a single algorithm," Seitz said.
Oncotype costs approximately $3,400 per test , so "we're definitely thinking much less than $1,700," Seitz said.
The next step for Applied Genomics is to study its assay in a clinical trial cohort, similar to the step Genomic Health took before Oncotype's launch, said Seitz. "They didn't do a clinical trial — they're doing that now — [but] what they did before was get access to a clinical trial cohort" with randomized patients who had been treated or untreated, he said.
Applied Genomics will not take the ASR route, which landed Genomic Health in a meeting with the US Food and Drug Administration to discuss its test's status. Instead, "we've begun the process of FDA clearance; we've filed a pre-IDE with the FDA already," Seitz said.
Applied Genomics, like some competitors making tests for node-negative, estrogen receptor-positive breast cancer, developed biomarkers for its test using microarrays, but plans to perform the actual test on patient samples with an older technology. In Applied Genomics' case, immunohistochemistry.
Oncotype Dx is run as an RT-PCR test in Genomic Health's reference laboratory. The clinical reliability of microarrays remains in doubt, despite the gains made by the technology through the FDA's clearance of Roche's AmpliChip CYP450.
RT-PCR provides "better sensitivity [and] specificity on an individual gene-by-gene basis," even for a 21-gene set, Randy Scott, CEO of Genomic Health told Pharmacogenomics Reporter sister publication BioArray News in February. RT-PCR is also a better technology for using RNA from formalin-fixed paraffin-embedded samples, he added.
Similarly, TriPath imaging and Orion are each developing breast cancer tests that will rely on PCR technology, although Orion's test is intended for detection.
Exceptions to the rule are Epigenomics, Veridex, and Agendia, whose multi-gene tests for breast cancer prognosis are designed to run on arrays in reference laboratories. Veridex' test relies on the expression patterns of 76 genes, while Agendia's relies on the expression of 70 genes.
Epigenomics "absolutely" plans to use Affymetrix' GeneChip for all of its tissue and pathology-based tests, including its breast cancer and prostate cancer prognostic tests, Christian Piepenbrock, the company's chief operating officer, told Pharmacogenomics Reporter this week. "That is the key to the whole story," he said.