Foundation Medicine Inc.'s Foundationone pan-cancer comprehensive genomic profiling assay will be reviewed via the FDA's Expedited Access Pathway. In addition, it will be evaluated for reimbursement via the FDA/Centers for Medicare & Medicaid Services (CMS) parallel review program.

As a result, the diagnostic will have a shorter review time, and should be eligible for nationwide Medicare reimbursement upon FDA approval. The Cambridge, Mass.-based company said it anticipates the parallel review will conclude in the second half of 2017.

The company performed 8,864 Foundationone tests during its recently completed quarter under the CLIA rules that govern laboratory-developed tests (LDT).

"We have separately made a voluntary decision to seek FDA-approval of our LDT," Lakshman Ramamurthy, Foundation Medicine's global regulatory lead, told BioWorld Today.

The decision coincides with signals that the FDA intends to increase its regulatory scrutiny of LDTs in the years ahead. Most notably, the agency in October 2014 released a draft guidance that described its plans to review LDTs. Finalization of the controversial guidance has stalled, but once a final version is released, the diagnostic tests performed in specialized laboratories will need to meet the FDA's stringent standards by demonstrating analytical and clinical validity.

Currently, tests carried out at the CLIA-certified labs do not require FDA approval, but some companies like Foundation Medicine are seeking it anyway, both in anticipation of the future and out of a desire to earn a regulatory gold star.

"We want to be an honest and diligent participant in patient health care," Ramamurthy said.

EXPENDITED REVIEW PROGRAM LENGTHENS ITS PIPELINE

Foundationone uses next-generation sequencing tools to detect genomic alterations, such as insertions, deletions, copy number alterations and gene rearrangements in hundreds of genes using DNA isolated from formalin-fixed paraffin-embedded tumor tissue specimens. In turn, the genomic data is used to guide the selection of targeted medications that are intended for patients with tumors that have specific genomic alterations.

"Upon successful completion of parallel review, Foundationone could become the first comprehensive genomic profiling assay, or CGP, to be FDA approved and with a national coverage determination for Medicare beneficiaries. We believe this universal companion diagnostic will be transformational by setting a new standard in assessing the molecular blueprint of cancer to better inform therapeutic options," Foundation Medicine CEO Michael Pellini said during the company's Aug. 2 second quarter earnings call.

"Our strategy is to remove the guesswork for physicians by providing a comprehensive view of CDx claims through Foundationone. Today, given the increasing number of single marker companion diagnostics, oncologists are quickly becoming overwhelmed with the complexity in selecting the appropriate test for each patient. Our test will be a single validated CGP assay of 324 genes, including a range of companion diagnostics, providing physicians with much of the necessary genomic information to point them to the relevant approved cancer therapeutics and do so with documented regulatory level quality," he continued.

Breakthrough devices that receive a review under the FDA's expedited access pathway are supposed to be approved (or rejected) quicker, and receive benefits such as priority review, more interactive review, senior management involvement and assignment of a case manager. In addition, and perhaps most importantly, the agency is more likely to be accepting of an abbreviated clinical trial. Ways in which clinical trials can be made smaller have been spelled out in a variety of FDA guidance documents, such as a July 2016 one on adaptive designs for medical device clinical studies.

Foundationone's acceptance into the program signifies that the FDA believes that the device is "intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition" and "offers significant, clinically meaningful advantages over existing legally marketed alternatives." Any plans for shorter clinical trials must be described in Foundation Medicine's data development plan, which the FDA must accept prior to submission into the program. Ramamurthy declined to disclose any details of the development plan.

In May, the FDA said it had accepted 17 devices for review under the expedited access program out of a total of 29 submissions at the program's one-year mark.

Finally action around parallel review program

The FDA's relationship with the device industry has steadily improved due to initiatives like the expedited access program, but the same can't be said about CMS, which has become increasingly restrictive about reimbursement of new devices and diagnostics.

FDA and CMS officials often talk about the need for interagency cooperation in a bid to speed up reimbursement decisions, and tout the parallel review program as the centerpiece of the initiative.

But since its inception in 2010, the program has resulted in one joint decision in 2014, that of Marlborough, Mass.-based Exact Sciences Corp.'s DNA-based Cologuard diagnostic for colorectal cancer, which simultaneously received FDA approval and a National Coverage Decision from CMS.

So, the addition of another diagnostic to the pipeline provides a boost to the program, whose funding has in the past been described as iffy.

Currently Foundationone receives nationwide coverage for analysis of non-small-cell lung cancer through a third party payer, and is broadly reimbursed for the analysis of a variety of tumors though a handful of regional players.

A National Coverage Decision from CMS would make the diagnostic available to all beneficiaries nationwide, Ramamurthy said. Typically there is a long lag time between FDA approval and nationwide CMS reimbursement, but due to the parallel program, both decisions should be announced simultaneously if all goes as planned.

"Upon completion [of the review process], we would expect approval across the entire Foundationone assay as well as a number of CDx claims. The initial claims may include FDA approved drugs for a range of solid tumor indications such as lung, breast, colon, gastric, ovarian and melanoma. These tumor types alone make up approximately 43 percent of the advanced metastatic patient population in the U.S. or more than 450,000 patients annually, which represents almost one-half of our total available markets," Pellini said.