NEW YORK (GenomeWeb) – Biocept last week launched OncoCEE-LU, its latest blood-based test designed to guide treatment strategies for lung cancer patients with ALK fusions who don't have sufficient tumor biopsy material for analysis by conventional tests.
The San Diego-based firm will offer OncoCEE-LU as a laboratory-developed test through its CLIA-certified lab, and will initially market it to leading oncologists in the lung cancer space who want to use a blood-based test in clinical diagnosis and research, Biocept CEO Michael Nall told GenomeWeb. Eventually, Biocept will market the test to pathologists and surgical oncologists.
Nall noted that he expects clinicians will use the test most readily to initially diagnose lung cancer patients who don't have sufficient tumor tissue samples or for whom it is unsafe to extract tissue, and to monitor disease when additional biomarker information is necessary.
Using reagents and microfluidic chambers, Biocept's "Cell Enrichment and Extraction" or CEE method captures circulating tumor cells from patient's blood samples. The CTCs can then be analyzed by fluorescence in situ hybridization (FISH) probes or via quantitative PCR methods.
The first indication for OncoCEE-LU is to gauge ALK fusions from CTCs. The ALK fusion status of a non-small cell lung cancer (NSCLC) patient is important to determine whether he or she will respond to ALK inhibitors, such as Pfizer's Xalkori (crizotinib) and Novartis' Zykadia (ceritinib).
The FDA approved Xalkori in 2011 with a tissue-based companion diagnostic, Abbott's Vysis FISH test. Meanwhile, Roche subsidiary Ventana markets an immunohistochemistry ALK test in China and other geographies outside the US.
The agency approved Novartis' Zykadia in April this year. The drugmaker, however, didn't pursue approval of Zykadia with its own companion test, choosing instead to rely on the tests already available on the market.
Since tissue-based diagnostics are the standard currently, Novartis' strategic decision makes sense from a resource standpoint since a recent study based on Medicare claims data suggests that biopsies are often the most expensive part of a lung cancer diagnostic workup. According to the study, the mean cost of a lung biopsy is $14,634, with average costs increasing to $37,745 when the costs of related complications are factored in. In this analysis presented at a recent medical conference, approximately 19 percent out of 1,700 patients receiving a lung biopsy experienced an adverse event, such as hemorrhage, pneumothorax, or respiratory failure requiring mechanical ventilation.
Industry observers have long noted that the one drug-one companion test model in personalized medicine is unsustainable for many cancer indications, such as lung cancer, where tissue resection can be problematic. As lung cancer advances, patients invariably develop resistance to the therapies that were once holding their disease at bay, and further molecular analysis may be necessary to figure out the new mutations driving their cancer and targeted treatment plans. But as patients' health fails and their bodies become weaker, it becomes risky and unethical to perform an invasive biopsy for further molecular analysis.
"You're not going to be monitoring patients [for disease progression] with a tissue-based diagnostic," Nall said.
Particularly in the case of Zykadia, the drug is approved for advanced NSCLC patients who have stopped responding to Xalkori. As such, the patients who receive this drug may need to be molecularly tested again to assess the characteristics driving their disease and making them unresponsive to Xalkori. For this more advanced NSCLC population, additional tissue biopsies could pose a challenge and a liquid biopsy test may be more fitting.
By the end of this year and in 2015, Biocept plans to expand the indication of OncoCEE-LU beyond ALK fusion testing in CTCs to assess other lung cancer markers such as EGFR mutations (i.e. T790M), ROS1 fusions, KRAS mutations, and EGFR and MET amplifications. In addition, future versions of the lung cancer test will also be able to analyze circulating tumor DNA in plasma, according to Nall.
The marketing strategy for the lung cancer test will likely be helped by the fact that Biocept in May hired a national sales force responsible for selling OncoCEE tests, and in August hired Amy McNeal to lead the company's test reimbursement strategies.
In addition to the lung cancer test, Biocept has launched OncoCEE-BR to help oncologists assess the enumeration of CTCs in breast cancer patients, as well as their HER2 status to determine whether they should receive HER2-targeted drugs such as Hercpetin (trastuzumab). The company also announced in October that it was expanding its collaboration with MD Anderson Cancer Center to use OncoCEE testing to capture CTCs and study the role of HER3 expression in ovarian cancer metastasis. Biocept is also planning to launch OncoCEE tests for melanoma, gastric, colorectal, and prostate cancer later this year or next year.
Although Biocept is commercializing OncoCEE-LU as an LDT, the company is aware that recently issued draft guidelines from the FDA may mean it has to file for regulatory clearance of approval of its tests. In the draft guidelines, the FDA has laid out a risk-based framework for regulating LDTs over a nine-year period, and has said that it considers tests that are used to guide therapeutic decisions to be high-risk devices requiring premarket review.
In the CTC diagnostics space, the FDA has cleared Janssen's CellSearch, a test that can identify and count CTCs and assess progression-free survival and overall survival in patients with metastatic breast, colorectal, or prostate cancer. Biocept claims its test captures more CTCs than CellSearch.
"There are a lot of changes [in the molecular diagnostics field] all the time," Nall said, adding that FDA's LDT guidance doesn't panic the company. He added that the company is gathering validation data on OncoCEE tests and working to remain prepared for regulatory requirements it might have to meet in the future. Although Biocept has yet to publish this data, Nall highlighted a positive predictive value of 75 percent for the lung cancer test.
According to its most recent 10-Q filed with the Securities and Exchange Commission, Biocept's average reimbursement payment per OncoCEE test is $1,512. However, the NSCLC test will include more biomarkers than the breast cancer test, according to the company, and this and a variety of other factors may impact the lung cancer diagnostic's pricing.