Originally published July 12.
By Turna Ray
Mammostrat, a breast cancer recurrence test developed by Applied Genomics, will be commercialized by Clarient starting in the fourth quarter.
Clarient told Pharmacogneomics Reporter this week that the company plans to initially launch Mammostrat as a laboratory-developed test gauging breast cancer patients' risk for recurrence.
"We will wait until we better understand the US Food and Drug Administration's requirements for filing before we take the test to the FDA," Clarient said, adding that the company is "prepared" to meet FDA's requirements whatever they may be.
FDA is holding a meeting next week to discuss its recently announced decision to extend regulatory oversight over LDTs in a risk-based fashion (PGx Reporter 07/07/10). Choosing to focus on the regulation of LDTs overall, the agency has said it will, for the time being, hold off on finalizing its draft guidelines for in vitro diagnostic multivariate index assays.
Mammostrat is a prognostic immunohistochemistry test that gauges the risk of breast cancer recurrence in postmenopausal, node-negative, estrogen receptor-expressing breast cancer patients who will receive hormonal therapy and are considering adjuvant chemotherapy. The IHC test analyzes five monoclonal antibody biomarkers and applies a diagnostic algorithm to assess whether patients have a high, moderate, or low risk of recurrence after they've had their breast cancer tumor surgically removed and have been treated with tamoxifen.
In acquiring Applied Genomics last year in a deal worth up to $17.6 million, Clarient gained access to several cancer diagnostics, among them Mammostrat (PGx Reporter 12/23/09). A spokesperson for Clarient expressed uncertainty as to whether Mammostrat would fall under FDA's current draft IVDMIA guidelines.
"As a prognostic test for risk recurrence, it is debatable whether it would actually fall under the current guidance," the spokesperson said. "It may, depending on your reading of that draft document. If the company plans to eventually make a chemotherapy response claim, it most definitely would fall under the current guidance document."
Upon its launch, Mammostrat will enter a breast cancer recurrence diagnostic market occupied by Genomic Health's Oncotype DX and Agendia's MammaPrint.
Oncotype DX is a real-time PCR-based test that assesses the expression of 21 genes in a patient's tumor sample and yields a recurrence score between 0 and 100 that translates into high risk, low risk, or intermediate risk for patients. Previous studies have shown that a low 21-gene recurrence score identifies patients with estrogen receptor-positive breast cancer who do not appear to benefit from CAF plus tamoxifen treatment despite positive axillary lymph nodes. The test is developed for women with node-negative, estrogen-receptor-positive invasive breast cancer, and for post-menopausal women with node-positive, hormone-receptor-positive invasive breast cancer.
MammaPrint is a microarray-based diagnostic that determines breast cancer patients' risk of disease recurrence based on a 70-gene signature panel. The test identifies early-stage breast cancer patients as either being at low risk or at high risk of distant recurrence following surgery, independent estrogen receptor status, and any prior treatment.
According to Clarient, Mammostrat has been validated in five studies involving more than 3,000 women, and the results from these studies allow the test to be used in the same patient cohort as other leading breast cancer prognostic tests on the market." In differentiating Mammostrat from competitors, Clarient is focusing on selling its test to pathologists, a group the company already has close ties with.
"Since Clarient currently is the 'go to' lab for the ER/PR and HER2 status for over 40 percent of women in the US, our approach is to offer pathologists a test that is equally 'powered' in clinical studies as the other two tests [Oncotype DX and MammaPrint] and can allow them to identify the recurrence risk without needed additional testing in over 80 percent of the cases."
This week, Clarient highlighted the publication of a study in Breast Cancer Research, in which researchers enrolled nearly 1,400 women after collecting their breast tissue samples in a study. Of the study participants, 197 received no adjuvant hormonal or chemotherapy, 1,044 women were treated with tamoxifen, and 149 women received a hormonal/chemotherapy combination regimen. The women's breast cancer tissue were then analyzed for five markers, p53, HTF9C, CEACAM5, NDRG1, SLC7A5, and their risk for breast cancer recurrence assessed by Mammostrat. Then researchers related the Mammostrat risk score to study participants' chances for relapse free survival and overall survival.
"Increased Mammostrat scores were significantly associated with reduced [relapse free survival and overall survival] in estrogen receptor-positive breast cancer," the researchers reported in the paper. Furthermore, multivariate analysis suggested that the risk score was independent of conventional risk factors for relapse-free survival and overall survival. "In node-negative, tamoxifen-treated patients, 10-year recurrence rates were 7.6+/-1.5% in the low-risk group versus 20.0+/-4.4% in the high-risk group," the researchers reported. "Further, exploratory analyses revealed associations with outcome in both ER-negative and untreated patients."
According to Clarient, the results of the study led by John Bartlett, a professor of molecular pathology at the University of Edinburgh in Scotland, "further validates the Mammostrat test as an aid for risk stratifying early stage hormone receptor-treated breast cancer patients." The study also suggests the added value of the test being able to stratify risk for node-positive patients and those who didn't express hormone receptors, Clarient adds.
In a statement, Bartlett highlighted Mammostrat as being "different from most risk classifiers in that it does not rely on measurement of surrogates for hormone receptor status, proliferation or tumor grade to risk-stratify." The test in Bartlett's view "offers the potential for a broader assessment of tumor aggressiveness by adding Mammostrat risk stratification to traditional risk classifiers."
Clarient Chief Medical Officer Ken Bloom further differentiated its test from competitors by pointing out that unlike other tests in the breast cancer recurrence space that "measure RNA from ground-up tumor tissue." In contrast, "Mammostrat measures protein expression specifically in the invasive tumor cells, ensuring biomarkers are expressed in the cells of interest," he said in a statement. This feature, according to Bloom is "very important in actual clinical practice," particularly for pathologists.
Although Clarient didn't provide an exact number for the price tag MammoPrint would carry, the company told PGx Reporter that it will seek value based pricing which will include testing on Mammostrat plus a complete(?) workup of the patient's tumor size, node status, grade, and ER/PR/Her2/Ki67 status.
Ahead of the test's launch, "Clarient had already engaged payors and we were told to come back once we had additional data," the company said. "Now [we] have data on Mammostrat in over 3,000 patients, well north of the number Mammaprint has, and close to the 4,000 patients that Oncotype has. We believe we can now approach both managed care payors and [the Centers for Medicare & Medicaid] with a solid story."