MSH2

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

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

Based on cancer biomarkers, the first-of-its-kind VENTANA MMR RxDx Panel helps identify solid tumour patients, including endometrial cancer patients, for treatment with Merck's immunotherapy KEYTRUDA. Roche Diagnostics Design Center, Mannheim. (Credit: F. Hoffmann-La Roche Ltd) Roche (SIX: RO, ROG;OTCQX: RHHBY) today announced US Food and Drug Administration (FDA) approval of a label expansion for the VENTANA MMR RxDx Panel. This approval advances the company’s commitment to personalised healthcare through tests that determine which patients are most likely to respond to specific and targeted therapies. The VENTANA MMR RxDx Panel is the first immunohistochemistry (IHC) companion diagnostic test to aid in identifying patients whose solid tumours are deficient in DNA mismatch repair (dMMR), and who may be eligible for KEYTRUDA® (pembrolizumab). The panel is also the first companion diagnostic test to aid in identifying endometrial cancer patients whose tumours are proficient in DNA mismatch repair (pMMR), and who may be eligible for a combination of KEYTRUDA and the tyrosine kinase inhibitor (TKI) LENVIMA® (lenvatinib). The test evaluates a panel of MMR proteins in tumours to provide important treatment information to clinicians. “Roche is committed to advancing personalised healthcare options for all solid tumour patients,” said Jill German, Head of Pathology, Roche Diagnostics. “As the first companion diagnostic of its kind, our test provides patients with access to multiple therapies, enabling targeted treatment. We are pleased that our innovative companion diagnostic portfolio continues to grow to serve more patients.” MMR is a naturally occurring mechanism that scans our DNA, correcting errors that cause disease. When MMR is deficient (dMMR), cells mutate, which can lead to cancer. While MMR deficiency is most common in endometrial cancer, other high-prevalence dMMR tumour types include gastric, colorectal, small intestine, cervical and neuroendocrine cancers. In the US, prevalence of dMMR across patients with solid tumours has been estimated at 14 percent.1 PD-1 inhibitors can be an effective treatment in cancers with MMR deficiency. For endometrial cancer patients without this MMR deficiency (pMMR) PD-1 inhibitors may retain activity when combined with a tyrosine kinase inhibitor (TKI). FDA approval of the label expansion for the VENTANA MMR RxDx Panel provides clinicians with access to a fully automated panel of MMR biomarkers tested by IHC. This label expansion follows the April 2021 FDA approval of the VENTANA MMR RxDx Panel as the first IHC predictive test to identify endometrial carcinoma patients eligible for treatment with the anti-PD1 immunotherapy JEMPERLI® (dostarlimab-gxly). That approval was expanded for the following indications on the dates below: August 2021 – dMMR solid tumour patients for treatment with JEMPERLI March 2022 – dMMR solid tumour patients for treatment with KEYTRUDA June 2022 – pMMR solid tumour patients for treatment with a combination of KEYTRUDA and LENVIMA Cancer is the second leading cause of death worldwide, with nearly 10 million deaths annually.2, 3 Endometrial cancer is the most common gynaecological cancer in the U.S. and the fourth most common cancer in women in North America.4 About the VENTANA MMR RxDx Panel This approval for the VENTANA MMR RxDx Panel is a label expansion of Roche’s current on-market panel. The VENTANA MMR RxDx Panel is intended for the assessment of expression of MMR proteins in formalin-fixed, paraffin-embedded (FFPE) tumour tissue stained with OptiView DAB IHC Detection Kit and ancillary reagents in the panel for VENTANA anti-MLH1 (M1), VENTANA anti-MSH2 (G219-1129) and VENTANA anti-MSH6 (SP93) and OptiView DAB IHC Detection Kit with the OptiView Amplification Kit and ancillary reagents for VENTANA anti-PMS2 (A16-4) on a BenchMark ULTRA instrument. DNA mismatch repair (MMR) proteins have been clinically proven to be predictive biomarkers for PD-1 targeted therapy; specifically, a loss of expression of one or more MMR proteins might predict an increased likelihood of response to such therapy.5,6,7 PD-1 inhibitors can be effective in cancers with MMR deficiency.5,7 MMR is a conserved molecular mechanism that functions to correct the improper base substitutions that spontaneously occur during DNA replication. Defects in the MMR machinery have been attributed to mutations in the MMR proteins. Read more about Roche’s innovation in MMR biomarker testing. Source: Company Press Release