FDA Grants Marketing Authorization to First DNA Test to Assess Genetic Predisposition to Select Cancers

Author(s):

The FDA has granted de novo marketing authorization for the Invitae Common Hereditary Cancers Panel, an in vitro diagnostic test designed to detect genetic variants associated with an elevated risk of developing certain types of cancer.

Additionally, the panel could also help identify potential cancer-associated variants in patients who have already been diagnosed with cancer.

The test utilizes DNA taken from a blood sample to identify the presence of variants in 47 genes that have demonstrated an association with an increased risk in developing certain types of cancer, including breast, ovarian, uterine, prostate, colorectal, gastric, melanoma, and pancreatic.²

The panel includes the following genes: APC, ATM, AXIN2, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, CTNNA1, DICER1, EPCAM, GREM1, HOXB13, KIT, MEN1, MLH1, MSH2, MSH3, MSH6, MUTYH, NBN, NF1, NTHL1, PALB2, PDGFRA, PMS2, POLD1, POLE, PTEN, RAD50, RAD51C, RAD51D, SDHA, SDHB, SDHC, SDHD, SMAD4, SMARCA4, STK11, TP53, TSC1, TSC2, and VHL. Notably, the test is designed to identify germline mutations and is not designed for the detection of somatic mutations in tumor tissue, according to Invitae.

This is the first device of its kind to receive marketing authorization from the FDA, according to the regulatory agency.¹

“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,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, stated in a news release. “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.”

The test is conducted with a sample collected at the point of care, and it is sent to a laboratory for testing.

The test was reviewed through the FDA’s de novo premarket review pathway, where Invitae conducted tests on more than 9000 clinical samples. The panel was found to have an accuracy of at least 99% for all test variants.

Specifically, the panel demonstrated analytical sensitivity and specificity of more than 99% for single-nucleotide variants, insertions, and deletions less than 15 bp in length, as well as exon-level deletions and duplications.2 Invitae noted that the test can detect insertions and deletions larger than 15 bp but smaller than a full exon; however, sensitivity for these could be marginally reduced.

Risks associated with the test include the possibility of false-negative and/or -positive results, as well as possible misinterpretation of the results, according to the FDA.¹

References

FDA grants first marketing authorization for a DNA test to assess predisposition for dozens of cancer types. News release. FDA. September 29, 2023. Accessed October 2, 2023. https://www.fda.gov/news-events/press-announcements/fda-grants-first-marketing-authorization-dna-test
Test catalog > Invitae Common Hereditary Cancers Panel. Accessed October 2, 2023. https://www.invitae.com/en/providers/test-catalog/test-01102