Let me briefly note a July 18, 2022, press release from Natera, announcing it has obtained bladder cancer coverage for its Signatera liquid biopsy test, from the MolDx program. Natera notes that it believes this is the first expansion in coverage under a MolDx LCD for minimal residual disease (MRD), which was published in December 2021.
Workers in this space should note that the coverage in the second half of 2022 appears to be based principally on 2019 and 2021 publications, which presumably Natera got to MolDx quickly. One study had 68 patients with over 600 plasma samples. The other study had nearly 600 patients with biosamples from an RCT. In short, Moldx coverage is not fast, not cheap, and not easy, even for one of the most experienced companies.
I'll put the link to the Natera press below, and quote the press release after the break.
Medicare Extends Coverage of Natera’s Signatera™ MRD Test to Muscle Invasive Bladder Cancer
AUSTIN, Texas, July 18, 2022 /PRNewswire/ — Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, today announced that it has received written confirmation from the CMS Molecular Diagnostics Services Program (MolDX) that the Signatera molecular residual disease (MRD) test has met coverage requirements for patients with muscle invasive bladder cancer (MIBC), effective April 19, 2022. To our knowledge, this represents the first coverage expansion to occur under the foundational local coverage determination (LCD) for MRD testing in solid tumors (LCD L38779), which was published in December 2021.
[ See the MolDx LCD online here: https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdid=38779&ver=4 ]
The decision by CMS in MIBC is based on evidence from multiple published validation studies. A study published in Nature, based on the phase III randomized IMvigor010 trial, showed that patients who tested MRD-positive after radical cystectomy received significant benefit from adjuvant immunotherapy, while MRD-negative patients derived no benefit from additional systemic therapy.
[See Powles et al., Nature 595:432, 2021. Evaluated 581 patients from a Phase III RCT].
Another study published in the Journal of Clinical Oncology found that serial testing with Signatera detected metastatic recurrence with 100% sensitivity and 98% specificity. Both studies showed that on-treatment monitoring with Signatera can provide an early assessment of therapy effectiveness, whether in the neoadjuvant or adjuvant settings.
"This is great news for patients with bladder cancer, who face uncertain treatment decisions throughout the patient journey," said Solomon Moshkevich, general manager of oncology at Natera. "This is also a milestone for Natera, representing the first new disease indication to be covered under the foundational LCD. We look forward to working with Medicare and with the oncology community to continue incorporating Signatera MRD assessment into standard care for patients with solid tumors."
Bladder cancer is the sixth most common cancer in the United States1 and MIBC represents 20-25% of the newly diagnosed cases.2 Patients previously treated for MIBC have a high rate of recurrence, with 50% experiencing distant recurrence post-cystectomy.3 Of these, 90% of recurrences develop in the first 3 years.4,5
"To balance the risks versus benefits of adding systemic treatments like chemotherapy to radical cystectomy, we need measures to identify which patients indeed harbor micrometastatic disease, which would allow refined shared medical decisions," said Matthew Galsky, M.D., professor of medicine (hematology and medical oncology), director of genitourinary medical oncology, co-director of the Center of Excellence for Bladder Cancer at the Tisch Cancer Institute and associate director for translational research at the Tisch Cancer Institute.
This decision adds to the existing Medicare coverage for Signatera in colorectal cancer and for pan-cancer immunotherapy monitoring.
Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for both clinical and research use, and has been granted three Breakthrough Device Designations by the FDA for multiple cancer types and indications. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. This maximizes Signatera’s accuracy for detecting the presence or absence of residual disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. Signatera is intended to detect and assess how much cancer is left in the body, to identify recurrence earlier and to help optimize treatment decisions.