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Mutations to the BRCA1 and BRCA2 genes significantly increase the chances of breast and ovarian cancers, and a test can assess a person’s risk from those variants. But those are just two genes of many known genetic drivers of cancer. The FDA has granted marketing authorization to an Invitae test that identifies the BRCA gene variants as well as dozens of others that can raise an individual’s risk of developing certain cancers. The Invitae Common Hereditary Cancers Panel assesses DNA extracted from a blood sample, using next-generation sequencing to assess 47 genes in a single test. The FDA said Invitae’s test is the first of its kind to receive marketing authorization, blazing a regulatory trail for future cancer tests. “Today’s action can provide an important public health tool that offers individuals more information about their health, including possible predisposition for certain cancers, which can help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Jeff Shuren, director of the FDA’s Center for Devices and Radiological Health, said in Friday’s announcement of the regulatory decision. The new test of San Francisco-based Invitae is a prescription product. A blood sample is collected at a site such as a doctor’s office, and then sent to a lab for testing. In addition to BRCA1 and BRCA2, other genes identified in the test include MLH1, MSH2, MSH6, PMS2 and EPCAM, which are associated with Lynch syndrome, an inherited disorder that increases the risk of colorectal cancer; CDH1, which is associated with hereditary diffuse gastric cancer and lobular breast cancer; and STK11, associated with Peutz-Jeghers syndrome, an inherited condition that raises the risk of cancers of the gastrointestinal tract. In Invitae’s tests to validate the performance of its Common Hereditary Cancers Panel, the company evaluated more than 9,000 clinical samples. Results showed greater than 99% accuracy for all tested types of variants. Even so, the FDA cautions that like any tests, there is a risk of false positive and false negative results, as well as possible misunderstanding of test results. The FDA said that the new Invitae test is not intended for identifying or evaluating all known genes associated with a predisposition to cancer. In those already diagnosed with cancer, the FDA said Invitae’s test can help identify potentially cancer-associated hereditary variants. The new Invitae test was reviewed under the de novo premarket review pathway. The FDA said authorization for the new test creates a new regulatory classification. Other tests of the same type and the same intended use may receive regulatory clearance through the FDA’s 510(k) regulatory pathway, as long as they can show they are substantially equivalent to the Invitae cancer test. The regulatory nod for Invitae’s new cancer test is a welcome bright spot for the company, which late last month received a New York Stock Exchange warning that its stock price, trading below $1 for 30 consecutive days, was not compliant with listing requirements. Invitae said at the time that it intends to bring the company into compliance with listing standards within the six-month period granted by the exchange. Invitae’s opening stock price Monday was 78 cents per share, up from 60 cents at market close Friday. Public domain image by the National Cancer Institute

Invitae's Common Hereditary Cancers Panel, which searches for hundreds of variants in 47 genes, received a de novo clearance from the FDA. Invitae has collected a de novo clearance from the FDA for a blood test designed to detect hundreds of potential genetic markers to help evaluate whether a person carries an increased risk of developing a range of certain cancers. While the act of parsing DNA for an inherited, cancer-linked mutation is nothing new for the diagnostic industry, the scale offered by Invitae’s test has defined a new product category going forward, the agency said in its announcement. “This test can assess multiple genes in a single test by using next-generation sequencing, which has proven helpful in providing insight into genetic variants with sensitivity and speed,” said Jeff Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health.  “Today’s action can provide an important public health tool that offers individuals more information about their health, including possible predisposition for certain cancers, which can help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Shuren added. The company’s Common Hereditary Cancers Panel searches for variants in 47 genes—including BRCA1 and BRCA2, which have been associated with hereditary breast and ovarian cancer, as well as genes connected with Lynch syndrome, which can trigger many types of tumors, including colorectal cancer. Other conditions include particular cancers of the digestive system, such as diffuse gastric cancer and tumors associated with Peutz-Jeghers Syndrome. The FDA noted that the prescription-only test does not evaluate all known genes that are connected to a predisposition to cancer and advised patients to discuss their results with a genetic counselor or other healthcare professional. The agency said that Invitae tested more than 9,000 clinical samples and found greater than 99% accuracy in validating the panel’s performance. The test can also help identify potentially hereditary variants in patients who have already been diagnosed with cancer. 

SILVER SPRING, Md., Sept. 29, 2023 /PRNewswire/ -- Today, the U.S. Food and Drug Administration granted de novo marketing authorization for the Invitae Common Hereditary Cancers Panel, an in vitro diagnostic test that can help detect hundreds of genetic variants associated with an elevated risk of developing certain cancers. The test can also help identify potentially cancer-associated hereditary variants in individuals with already-diagnosed cancer. The test, which is the first of its kind to be granted FDA marketing authorization, evaluates DNA extracted from a blood sample to identify variants in 47 genes known to be associated with an elevated risk of developing certain types of cancer. "This test can assess multiple genes in a single test by using next-generation sequencing, which has proven helpful in providing insight into genetic variants with sensitivity and speed," said Jeff Shuren, M.D., J.D., director of the FDA's Center for Devices and Radiological Health. "Today's action can provide an important public health tool that offers individuals more information about their health, including possible predisposition for certain cancers, which can help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants." According to the Centers for Disease Control and Prevention, there are more than 100 different documented types of cancer, a disease in which abnormal cells divide out of control and are able to invade other tissue. It is the second leading cause of death in the United States behind heart disease. The Invitae Common Hereditary Cancers Panel can be used as a tool to help identify inherited causes of various types of cancers. Patients should speak with a healthcare professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results. Importantly, this test is not intended to identify or evaluate all known genes that can provide insight into predisposition for cancer. For this prescription test, the specimen is collected at the point of care, such as a doctor's office, and sent to a laboratory for testing. The clinical interpretation of the variants is based on evidence from published literature, public databases, prediction programs and Invitae's internal curated variants database using Invitae's variant interpretation criteria consistent with those established by appropriate professional organizations or accredited boards. Some of the most clinically significant genes that the test identifies are: BRCA1 and BRCA2, which are genes with known associations to hereditary breast and ovarian cancer syndrome, Lynch syndrome associated genes (MLH1, MSH2, MSH6, PMS2 and EPCAM), CDH1 (mainly associated with hereditary diffuse gastric cancer, and lobular breast cancer) and STK11 (associated with Peutz-Jeghers Syndrome). The FDA reviewed the Invitae Common Hereditary Cancers Panel under the FDA's De Novo premarket review pathway, a regulatory pathway for low- to moderate-risk devices of a new type. To validate the performance, Invitae tested over 9,000 clinical samples, and achieved ≥99.0% accuracy for all tested variant types. The risks associated with the test are mainly the possibility of false positive and false negative test results, as well as possible misunderstanding of the results. False negative test results may provide a false sense of assurance and these patients may not receive appropriate surveillance or clinical management. False positive test results could lead to inappropriate decision-making regarding healthcare and lifestyle, which can be associated with other undesirable clinical consequences. Further, since this test is not intended to identify or evaluate all known genes associated with a predisposition for cancer, and genetics are not the only factor in development of cancer, there is a risk of patients misunderstanding that they still have some risk of developing cancer following a negative test result. These risks are mitigated by the analytical performance validation, clinical validation and appropriate labeling of this test. Along with this De Novo authorization, the FDA is establishing special controls that define the requirements related to labeling and performance testing. For example, accuracy for reporting of substitutions, insertions/deletions and copy number variants must be ≥99.0% for positive agreement and ≥99.9% for negative agreement with a validated orthogonal method. When met, the special controls, in combination with general controls, provide a reasonable assurance of safety and effectiveness for tests of this type. Today's action creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through FDA's 510(k) premarket process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device, which may save a developer time and expense compared to other review pathways. # # # Media Contact: Jim McKinney, 240-328-7305 Consumer Inquiries: 888-INFO-FDA The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products. SOURCE U.S. Food and Drug Administration