This article has been updated to clarify the launch date of NavDx and Naveris' billing policies for patients without insurance coverage.
NEW YORK – Naveris this week said that its NavDx circulating tumor tissue-modified HPV DNA blood test is now covered by Medicare for surveillance in head and neck cancer patients who are minimal residual disease (MRD)-negative following treatment.
The test is covered under an existing local coverage determination from the MolDx program, which establishes coverage and reimbursement policies for molecular diagnostic tests for participating part A/B Medicare administrative contractors. Naveris' management hopes the decision, coming about three years after it launched the test, will prompt bodies such as the National Comprehensive Cancer Network (NCCN) and the American Head and Neck Society to include it in their practice guidelines.
NavDx is the first MRD test covered for Medicare beneficiaries with HPV-driven oropharyngeal cancer to detect recurrence of disease, beginning three months after standard radiation and chemotherapy treatment, according to Naveris.
"For a small company like ours, [Medicare coverage] is a transformational moment," said Naveris CEO James McNally. "It really validates years of work that our team have done to demonstrate the technical performance and clinical utility of the assay."
Catching cancer recurrence early with the help of a test like NavDx could potentially improve a patient's survival or allow the patient to de-escalate treatment. "The morbidity associated with some of the treatments for head and neck cancer can be quite severe and have lifelong effects," McNally said.
Current surveillance guidelines from NCCN state that patients should undergo endoscopy with a clinical exam every one to three months in the first year after completing treatment, every two to six months in the second year, and about once a year thereafter, and have a baseline imaging scan within six months of treatment. Follow-up scans are only recommended for patients with signs or symptoms of recurrence.
NavDx compares very favorably and is in fact superior to those surveillance methods, according to Naveris Chief Medical Officer Barry Berger. "The sensitivity and specificity [of NavDx] are in the 90s in the surveillance setting," Berger said.
He pointed out that while there are "good reasons" for follow-up exams, especially in the early months after surgery, standard screening tools have limitations. "What we've seen and others have reported is that [standard] surveillance, especially in asymptomatic patients, is extremely insensitive," which he said makes sense because many recurrences are in the lungs, "and you certainly aren't going to find those by doing your endoscopy exams."
In July, researchers from Icahn School of Medicine at Mount Sinai published results of a retrospective study exploring the use of NavDx for diagnosis and surveillance in head and neck cancer patients in JAMA Otolaryngology-Head & Neck Surgery. In 163 patients in the diagnostic cohort, the NavDx test had sensitivity of 91.5 percent and 100 percent specificity. In the 290-patient surveillance cohort, the test showed sensitivity of 88.4 percent and 100 percent specificity for detecting recurrences. The positive predictive value of the test was 100 percent, and the negative predictive value was 99.1 percent.
For comparison, the negative predictive value of a single PET/CT scan with negative findings within six months of completing treatment was reported to be 91 percent in a 2013 study in the American Journal of Neurology. In another study published in 2020, the positive predictive value of a post-treatment PET/CT imaging in that setting was 56 percent.
Berger said the reason NavDx is able to achieve such high sensitivity and specificity is that it is able to measure as few as two or three tumor tissue-modified HPV viral fragments per milliliter of plasma. That, in his view, makes MRD diagnosis possible at a much earlier stage than a recurrence could be detected via standard surveillance.
Since commercially launching the test in 2021, Naveris has worked steadily to promote adoption of its test. Berger said that currently over a thousand doctors, including ear, nose, and throat surgeons and medical and radiation oncologists, are using NavDx in daily practice. Over 400 sites across the US regularly order the test, Berger noted, including all 31 NCCN cancer centers that treat adult patients.
Unlike most other cancers that are decreasing in annual incidence, Berger pointed out that the rates of newly diagnosed head and neck cancers have been increasing at about 2 percent to 3 percent each year. "This is a function of a long latency," Berger said, explaining that these tumors develop slowly over a period of 20 years or more, and the HPV vaccine is still not widely used by men.
Rates of head and neck cancer had been declining by about 14 percent overall since 1975, mainly due to decreasing tobacco use. However, after a low point in 2003, the rates increased by 15.5 percent, driven by increasing HPV-related disease. There were around 54,000 new cases of head and neck cancer last year. Berger estimated that HPV vaccination programs will not curb the rising rates of the disease until 2050 or 2060.
Glenn Hanna, a medical oncologist at Dana-Farber Cancer Institute, uses NavDx in the care of every HPV-positive head and neck cancer patient in his practice, including those who are newly diagnosed, have advanced disease, are on treatment, or are being surveilled for recurrence. "I use it as a clinical decision-making tool complementing their exam and imaging findings in every patient I treat," Hanna said.
In a paper published in Clinical Cancer Research in October, Hanna calculated the negative predictive value of NavDx for recurrence when matched to physician-reported clinical outcomes data at a median follow-up time of 27.9 months. The sensitivity of the assay was 92.5 percent per test, and the negative predictive value was 99.4 percent, meaning that the test gave very few false-negative results and missed few recurrences.
That work complements a similar retrospective study published by Berger, Hanna, and other collaborators in Clinical Cancer Research in 2022 involving more than 1,000 patients showing that the test had a positive predictive value of 95 percent.
Hanna said in his practice both negative and positive results from NavDx have value for patients. A negative result can eliminate the need for additional exams and imaging, and a positive result "should trigger a search for occult malignancy," Hanna said.
Given the accumulating data in the published literature and his own clinical experience, Hanna expressed surprise that NCCN doesn't already recommend circulating tumor tissue-modified HPV ctDNA testing in the surveillance setting for HPV-driven head and neck cancer.
"There are other treatments that come within the guideline that potentially have the same amount of data … that get attention in that document," Hanna said. "I don't understand why, given the amount of data that's [emerged] in several years, this testing wouldn't [be included], as well."
Although Hanna and other physicians have used NavDx extensively in clinical practice, only recently has Naveris begun pursuing reimbursement with commercial payors. For patients without insurance coverage, McNally maintained that Naveris does not seek payment from patients. Some patients with insurance that Hanna ordered NavDx for, however, were sometimes responsible for a substantial copayment, he said, while others without insurance did not receive additional bills for the test.
The latest Medicare coverage substantially improves the reimbursement environment for NavDx and should ease access for a subset of patients, according to Naveris. "HPV-positive head and neck cancers tend to impact an older population," McNally said. "Our patient population tends to skew towards the Medicare population."
Now that Medicare coverage is established, Naveris is focusing on garnering favorable coverage policies from commercial payors. McNally expressed confidence that the "extraordinarily rigorous" MolDx process will signal to commercial payors that the test has clinical utility. "I would hope that carries over," McNally said.
With newly published data on NavDx's clinical utility for surveillance and Medicare coverage in place, Berger said he's "cautiously optimistic that NCCN … will assess NavDx as equivalent or better than the currently recommended periodic clinical exams."
Naveris is exploring other applications for NavDx, such as tailoring treatment and de-intensifying therapy for patients with HPV-related head and neck cancer, and studying the test in different cancer settings, such as screening and surveillance of gynecologic cancers.
Berger said NavDx has also shown promise in HPV-driven anal cancer. "Some gastroenterologists who follow [anal cancer] patients are already using the test to a limited degree," Berger said, adding that this setting will be Naveris' "next target" for developing NavDx as a diagnostic and surveillance tool. The firm is in negotiations with the investigators of a clinical trial, dubbed ANCHOR, to access samples and conduct a retrospective study in anal cancer.