- CMS on Monday finalized a national decision to cover FDA-authorized next generation sequencing-based tests in patients with all stages of germline, or inherited, breast or ovarian cancer.
- The agency first began covering the precision genetic tests in 2018 for certain advanced cancers. Amid criticism that the policy was too narrow, the agency in 2019 opened consideration of widening coverage to earlier stage cancers.
- While CMS declined to expand coverage in the final version to cancer types beyond breast and ovarian, citing insufficient evidence of clinical utility, the agency is leaving it up to local Medicare contractors to make coverage determinations for patients with other germline cancer diagnoses and on tests that have not been greenlighted by FDA, which may provide leeway as the field evolves and new evidence emerges.
A single NGS test can analyze DNA for millions of genomic variations that can reveal an individual's risk for developing certain genetic diseases, which could potentially help guide treatment.
NGS-based IVDs gained momentum with FDA's late 2017 approval of Foundation Medicine's FoundationOne CDx, which acts as a companion diagnostic in part for ovarian cancer treatments. CMS simultaneously proposed coverage for the test under the Parallel Review Program. Foundation was subsequently acquired by Swiss pharma giant Roche.
Companies that don't have FDA approval or clearance for their NGS-based IVDs may stand to benefit from the flexibility in the final decision, one example being Invitae.
The "finalized document no longer requires that hereditary breast and ovarian tests have FDA approval (PMA) or FDA clearance (510k) to ensure coverage. This update is clearly a positive for [Invitae], since the company's current tests are neither FDA approved or cleared," Cowen analyst Doug Schenkel wrote in a note Monday.
"CMS recognizes that innovation is happening quickly and evidence is moving fast, and the agency wanted to ensure that patients have ready access to this diagnostic test when appropriate," the agency said Monday.
CMS in March 2018 said it would cover NGS-based diagnostic tests for patients with recurrent, metastatic, relapsed, refractory, stage III or stage IV cancer — altogether referred to as advanced cancer. The agency said that even in cases when a patient could not be matched to an FDA-authorized treatment, information from NGS testing could help match a patient to a clinical trial.
Later that year, FDA finalized two guidances for manufacturers regarding how to use public human genetic variant databases to back clinical validity of genetic and genomic-based in vitro diagnostics, and considerations for the design, development and analytical validation of NGS IVDs meant to help diagnose germline diseases.
Last spring, CMS initiated a review of NGS testing for Medicare beneficiaries with advanced cancer, with an initial 30-day comment period between late April and May that garnered more than 80 comments from provider organizations, labs, manufacturers, patient advocates and others.
CMS outlined plans to widen NGS test coverage to Medicare beneficiaries with earlier stage germline cancers in the proposed coverage decision issued in late October. While the draft was well received by industry, more than 40 commenters still had ideas for changes, including companies like Foundation Medicine and Invitae, as well as Caris Life Sciences, Illumina and Adaptive Biotechnologies.
One concern was that coverage was restricted to patients who had never previously received NGS testing, which CMS addressed in the final decision by narrowing the language to say that eligible patients must not have been previously tested "with the same germline test using NGS for the same germline genetic content."
CMS declined to add other types of cancer to the NCD.
"At this time, there is insufficient evidence of clinical utility for other cancer types including male breast cancer, colorectal, lung, pancreatic and prostate cancer and we acknowledge the evidence in this field is rapidly developing," the agency wrote in the final decision memo.
Under the decision, patients will qualify if they have ovarian or breast cancer; if they have a clinical indication for germline testing for hereditary ovarian or breast cancer; or if they have a risk for germline ovarian or breast cancer, and have not been previously tested with the same germline test using NGS for the same germline genetic content, CMS said.