Genomic Health's Oncotype Dx has a high profile in the molecular diagnostics market, and though the test is currently playing nearly unopposed, a number of rivals are using it as a blueprint of sorts to help them develop their own diagnostics for breast cancer recurrence.
During Cambridge Healthtech Institute's Tri-Conference last week in San Francisco, Genomic Health CEO Randy Scott spoke about the company's data validation procedure for the test. But Oncotype Dx isn't perfect, and the competition is trying to get fierce.
In fact, three speakers in the breast cancer diagnostics segment during which Scott spoke were employees of Oncotype competitors, and they made it no secret that they hope to beat Genomic Health at its own game.
"Genomic Health is raising the tide for everybody — everybody's going up with them," said Jorge León, president of the consulting firm Leomics and acting chief scientific officer and vice president of business development of Orion Genomics. "I really applaud what they are doing." But competing firms now have a "gold standard to weigh against," and they have a reference price that "is very high," León said.
Competitors can enter the market at a high price or decide to attract more customers with a cheaper test, he said, adding that he thinks "other people will develop better tests, or Genomic Health itself will develop better tests."
Genomic Health is "proving the principle with a not-so-good test, but they're doing a fantastic job at packaging it."
Despite a recent letter from the US Food and Drug Administration that raised the question of whether Genomic Health should have pursued pre-market clearance for its Oncotype test, the company is still the leader of the pack for clinically validating, marketing, and winning reimbursement for the breast cancer test.
Oncotype was designed to help clinicians decide what actions to take after breast cancer treatment by giving them an idea of the chance of recurrence based on the expression levels of 21 genes measured by RT-PCR. Chemotherapy is often the treatment for patients whose cancer is likely to recur or metastasize.
One potential Genomic Health rival is Applied Genomics, which is working on an immunohistochemistry test for classifying tumors by type as a means to identify the risk of recurrence. "We're not the only ones" working on an early-stage breast cancer prognosis test, said Doug Ross, Applied Genomics CSO, in an interview last week. Due to the clinical need, "there are a number of folks working on it."
Relying on gene-expression data from paraffin-embedded tissue samples, Applied Genomics narrowed down a field of antigens to a final group of five that it believes will be able to distinguish tumors in a way that will provide predictive information about disease recurrence, said Ross.
Also speaking at the conference were representatives from TriPath Imaging, which is working on a breast cancer-recurrence assay using imaging biomarkers; Veridex, which is working on an assay that uses a 76-gene expression signature to assess recurrence risk in estrogen receptor-positive and -negative patients using fresh frozen tumor samples; and Agendia, whose MammaPrint test is intended to use a 70-gene expression profile to assess recurrence risk in ER-positive and -negative patients from fresh and frozen material. MammaPrint is available in Europe, but not yet in the United States.
Leon's Orion Genomics is also working on a breast cancer test using epigenetic biomarkers, though that assay is intended to screen for early signs of disease rather than help nail down prognoses.
David Ransohoff, an epidemiologist at the University of North Carolina, Chapel Hill, told Pharmacogenomics Reporter sister publication GenomeWeb News this week that Genomic Health's success in developing the OncotypeDx test has "outlined a kind of model that the field can learn from."
Genomic Health is "proving the principle with a not-so-good test, but they're doing a fantastic job at packaging it — they are the Starbucks of personalized medicine, [which is] charging four bucks for the same coffee you can get somewhere else," said León.
But not everyone believes the test will help competitors. "What they've done is a very different assay than what is conventionally done in current clinical diagnostics, so my understanding is that they're not seeking FDA [clearance],"said Ross. "What [Applied Genomics] is doing is something that is much more conventional in the diagnostic world — we're developing an immunohistochemistry assay … so our strategy is likely to be much different," he said.
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," said Ross.
Genomic Health, by comparison, plans to offer Oncotype through its own reference lab.
Applied Genomics hopes to finish an independent clinical study this year, with an independent statistical analysis, Ross said. Only then will the company decide whether to file for FDA clearance.
Representatives from Veridex and TriPath were unable to respond to questions before deadline.
Pros and Cons of the Only Test on the Block
The fact that Oncotype is the first to market in early-stage breast cancer-recurrence testing may work to competitors' advantages in some ways. The fact that there are no IHC tests on the market is "what's going to create the market need, which is currently being filled only by Genomic Health," said Ross. The IHC test would likely be less expensive, as well, he added. The test currently costs $3,460.
In its favor, Genomic Health has really gotten Oncotype's clinical validation right, according to León. "Whatever the test's information is, they have been extraordinarily honest and straight about the limitations of the test and the advantages and the statistical management that the test is not a perfect test," he said.
Genomic Health has "the best" clinical data, it has conducted good clinical trials, and it has presented known biomarkers for breast cancer recurrence in a statistically significant manner where others have not, León said. Oncotype Dx recurrence scores range from zero to 18 for patients having a low risk of recurrence, 19 to 30 for an intermediate risk, and 31 and above for high risk. Patients in the test's clinical validation study with score of 10 — approximately in the middle of the low-risk range — had an average recurrence rate after 10 years of 7 percent, with a confidence interval of 4 percent to 9 percent, according to a sample Oncotype Dx report.
But in patients with low recurrence scores, some are going to have their cancers recur. "So, if I was a patient, I would not take any risk [with a low recurrence score]. Would you?" said León.
Steve Shak, Genomic Health CSO, said in an interview that the test is not intended to be relied upon as a single basis for chemotherapy decisions, and that the risk determination helps to provide doctors more information about the risk of recurrence for low-risk patients. "We've gotten feedback [based on a NSABP study of Oncotype] that the confidence intervals [for individual recurrence scores] not only were relatively tight, but we did a second study with Kaiser Permanente — they looked at the risk of breast cancer death. In the low-risk group in that study, the rate of breast cancer death … was 2.8 percent in 10 years, with very tight confidence intervals," he said.
In a situation León likened to Digene's entrenched position in the human papilloma virus testing market, Genomic Health will probably be ahead of its competitors for a long time, having achieved early technical success, along with publications and endorsements from clinicians. But despite this lead, he said he doesn't "think they will penetrate 100 percent — not even 50 percent" — of the early-stage breast cancer prognostic market due to the test's uncertainties, high price, and as-yet incomplete reimbursement.
Kim Popovits, Genomic Health COO, said Oncotype's validation will keep it secure from much of the competition. But "to the extent that somebody can come along and do a test that has that level of clinical validation, and can answer both the response to chemotherapy and the recurrence [risk], we absolutely expect that there will be competitors in the space," she said.
— Chris Womack ([email protected])