FDA announces approval, CMS proposes coverage of first breakthrough-designated test to detect extensive number of cancer biomarkers

The U.S. Food and Drug Administration today approved the FoundationOne CDx (F1CDx), the first breakthrough-designated, next generation sequencing (NGS)-based in vitro diagnostic (IVD) test that can detect genetic mutations in 324 genes and two genomic signatures in any solid tumor type. The Centers for Medicare & Medicaid Services (CMS) at the same time proposed coverage of the F1CDx. The test is the second IVD to be approved and covered after overlapping review by the FDA and CMS under the Parallel Review Program, which facilitates earlier access to innovative medical technologies for Medicare beneficiaries.

"By leveraging two policy efforts aimed at expediting access to promising new technologies, we've been able to bring patients faster access to a breakthrough diagnostic that can help doctors tailor cancer treatments to improve medical outcomes and potentially reduce health care costs," said FDA Commissioner Scott Gottlieb, M.D. "The FDA's Breakthrough Device Program and Parallel Review with CMS allowed the sponsor to win approval for this novel diagnostic and secure an immediate proposed Medicare coverage determination within six months of the FDA receiving the product application."

Compared to other companion diagnostics previously approved by the FDA that match one test to one drug, the F1CDx is a more extensive test that provides information on a number of different genetic mutations that may help in the clinical management of patients with cancer. Additionally, based on individual test results, the new diagnostic can identify which patients with any of five tumor types may benefit from 15 different FDA-approved targeted treatment options. Its results provide patients and health care professionals access to all of this information in one test report, avoiding duplicative biopsies. 

"The F1CDx can help cancer patients and their health care professionals make more informed care decisions without the often invasive process of extracting tumor samples multiple times to determine eligibility for a single treatment or enrollment in a clinical trial," said Jeffrey Shuren, M.D., director of the FDA's Center for Devices and Radiological Health (CDRH). "With the run of one test, patients and health care professionals can now evaluate several appropriate disease management options."  

Today, CMS also issued a proposed national coverage determination of the F1CDx and other similar NGS IVDs for Medicare beneficiaries with advanced cancer (i.e., recurrent, metastatic or advanced stage IV cancer), who have not been previously tested using the same NGS technology and continue to seek further cancer therapy. The proposed national coverage determination provides coverage of NGS IVD tests to assist patients and their treating physicians in making informed cancer treatment decisions that improve health outcomes. Use of a test as a diagnostic also includes the ability to help patients and their treating physicians determine candidacy for cancer clinical trials.

"Through parallel review and collaboration, we speed access to innovative diagnostics, so that doctors are better able to deliver the best quality care to their patients and patients have access to these state-of-the-art tests," said Seema Verma, Administrator of CMS. "Our proposal establishes clear expectations, while at the same time delivering better outcomes for the people we serve."

This determination was made under the FDA-CMS Parallel Review Program, where the agencies concurrently review medical devices to help reduce the time between the FDA's approval of a device and Medicare coverage. This voluntary program is open to certain premarket approval applications for devices with new technologies and to medical devices that fall within the scope of a Part A or Part B Medicare-benefit category and have not been subject to a national coverage determination.

The F1CDx detects gene mutations that may be found in any solid tumor and this information can be used by physicians according to professional guidelines to manage cancer patients. Moreover, it can be used as a companion diagnostic to identify patients with specific mutations who may benefit from certain FDA-approved treatments for non-small cell lung cancer, melanoma, breast cancer, colorectal cancer or ovarian cancer. Importantly, the F1CDx can detect genetic mutations that are indicated for multiple FDA-approved treatments, which extends beyond the previous "one test for one drug" model.

The device works by sequencing DNA from a patient's tumor sample to determine the presence of gene mutations and alterations. It also detects certain molecular changes (microsatellite instability and tumor mutation burden). Clinical performance of the test was established through a least burdensome means by comparing the F1CDx to previously FDA-approved companion diagnostic tests that are currently used to determine patient eligibility for certain treatments. Results indicated that the test's ability to detect select mutation types (substitutions and short insertions and deletions) representative of the entire 324 gene panel is accurate approximately 94.6 percent of the time.

The F1CDx had not been previously submitted for the FDA's review because it is a laboratory-developed test, for which the agency has generally not enforced premarket review and other applicable requirements. However, at the test developer's request, the FDA worked closely with them to help enter it into the agency's newly established Breakthrough Device Program. Because of the test's potential to consolidate multiple companion diagnostic claims for patients and health care providers in a single test, the F1CDx was granted Breakthrough Device designation. Under the Breakthrough Device Program, the FDA provides intensive interaction and guidance to the company on efficient device development, which expedites evidence generation and the agency's review of devices that provide for more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases for which no approved or cleared treatment exists or that offer significant advantages over the existing standard of care.

The FDA also reviewed the F1CDx application using a coordinated, cross-agency approach; the clinical review was conducted by FDA's CDRH with support from FDA's Oncology Center of Excellence, while all other aspects of review and the final product approval determination was conducted by the FDA's CDRH. 

The FDA granted approval for the F1CDx test to Foundation Medicine, Inc.

For more information:
FDA: PMA Approvals
FDA: CDRH's Approach to Tumor Profiling Next Generation Sequencing Tests
FDA: Medical Devices Expedited Access Pathway Program
FDA/CMS: Program for Parallel Review of Medical Devices
CMS: Medicare Coverage Center
CMS: National Coverage Analyses (NCAs) Alphabetical Index
CMS: Public Comments

The FDA, an agency within the U.S. Department of Health and Human Services, promotes and protects the public health by, among other things, 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.

The CMS, an agency within the U.S. Department of Health and Human Services, directs the planning, coordination, and implementation of the programs under the Social Security Act and related statutes, to administer Medicare, Medicaid, the Children's Health Insurance Program (CHIP), and the Health Insurance Marketplace. The agency also directs the development of effective relationships between these programs and private and federally supported health-related programs.