FDA has granted premarket approval for the FoundationOne CDx (F1CDx) in vitro diagnostic from Foundation Medicine Inc, Cambridge, Mass. The next-generation sequencing (NGS) test can detect genetic mutations in 324 genes and two genomic signatures in any solid tumor type.

The Centers for Medicare and Medicaid Services (CMS) at the same time proposed reimbursement coverage for the F1CDx test. The test is the second in vitro diagnostic to be approved and covered after overlapping review by FDA and CMS under the agencies’ parallel review program, which facilitates earlier access to innovative medical technologies for Medicare beneficiaries.

Scott Gottlieb, MD, FDA.

Scott Gottlieb, MD, FDA.

“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 healthcare costs,” says FDA Commissioner Scott Gottlieb, MD. “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 6 months of FDA receiving the product application.”

Compared to other FDA-approved companion diagnostics that match one test to one drug, F1CDx is a more-extensive test, and provides information about 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 healthcare professionals access to all of this information in a single test report, avoiding duplicative biopsies.

Jeffrey Shuren, MD, JD, Center for Devices and Radiological Health.

Jeffrey Shuren, MD, JD, Center for Devices and Radiological Health.

“F1CDx can help cancer patients and their healthcare 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,” says Jeffrey Shuren, MD, JD, director of FDA’s Center for Devices and Radiological Health (CDRH). “With the run of one test, patients and healthcare professionals can now evaluate several appropriate disease management options.”

CMS’s proposed national coverage determination for F1CDx will also apply to the use of other similar NGS diagnostics for Medicare beneficiaries with advanced cancer (ie, recurrent, metastatic, or advanced stage IV cancer) who have not previously been tested using NGS technology and are continuing to seek further cancer therapy. The proposed national coverage determination will provide reimbursement coverage for NGS tests to assist patients and their treating physicians in making informed cancer treatment decisions that improve health outcomes. Use of such diagnostics also helps 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,” says CMS Administrator Seema Verma. “Our proposal establishes clear expectations, while at the same time delivering better outcomes for the people we serve.”

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

F1CDx detects gene mutations that may be found in any solid tumor. Following professional guidelines, physicians can use this information to manage the care of cancer patients. Moreover, F1CDx can be used as a companion diagnostic to identify patients with specific mutations who may benefit from certain FDA-approved treatments for breast cancer, colorectal cancer, melanoma, non-small cell lung cancer, or ovarian cancer. Importantly, F1CDx can detect genetic mutations that are indications for multiple FDA-approved treatments, extending approved use of the test beyond the previous ‘one test for one drug’ model.

F1CDx works by sequencing DNA from a patient’s tumor sample to determine the presence of gene mutations and alterations. It also detects such molecular changes as microsatellite instability and tumor mutation burden. Clinical performance of the test was established by comparing F1CDx to previously FDA-approved companion diagnostics 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% of the time.

Troy Cox, Foundation Medicine.

Troy Cox, Foundation Medicine.

Foundation Medicine CEO Troy Cox called the parallel review decision from FDA and CMS “historic,” saying that it represents a major advance in personalized cancer care. “Physicians will have an FDA-approved test for all solid tumors in their toolkit that can inform targeted and immunotherapy selection, as well as identify patient opportunities for clinical trial participation,” Cox said. “Beyond its implications for patient care, we expect that FoundationOne CDx will provide biopharma companies with an FDA-approved platform that can help accelerate drug development and enable personalized oncology care.”

F1CDx had not been previously submitted for FDA review because it is a laboratory-developed test, for which the agency has historically not enforced premarket review and other applicable requirements. At the request of the test developers, however, 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 healthcare providers in a single test, F1CDx was granted breakthrough device designation. Under the breakthrough device program, FDA provides intensive interaction and guidance to the company on efficient device development. The program expedites evidence generation and the agency’s review of devices that provide for more-effective diagnosis or treatment of 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 approval of F1CDx represents a major advance in the personalization of cancer care, facilitating access for patients in the United States to a comprehensive pan-tumor companion diagnostic that will help identify approved treatment options based on the molecular footprint of each individual’s cancer,” says Sandra Horning, MD, chief medical officer at Roche and head of global product development. “Our belief is that profiling will increasingly become routine in clinical practice, so we have worked closely with Foundation Medicine to develop an extensive clinically and analytically validated platform that can support both existing and future companion diagnostic needs.”

FDA also reviewed the F1CDx application using a coordinated, cross-agency approach. Clinical review was conducted by CDRH with support from the agency’s oncology center of excellence, while all other aspects of review and the final approval determination were completed by CDRH.

FoundationOne CDx is expected to be commercially available following finalization of the CMS national coverage determination.