NEW YORK (GenomeWeb) – With a recent draft guidance from Medicare contractor Palmetto GBA proposing coverage of its second-generation Xpresys Lung test, Integrated Diagnostics is now embarking on clinical utility studies with the aim of launching the test commercially within the next six to nine months.
Indi also said this week that it has raised $6.1 million in Series C funding from Bird Capital and InterWest Partners that it will use to fund the last phases of its efforts to secure Medicare coverage of the test. The company is now planning additional fundraising to support the test's commercialization, said Indi CEO Albert Luderer, adding that it hoped to raise in the range of $30 million to $40 million.
The new test, called Xpresys Lung 2, is a refined version of Indi's orginal Xpresys test, which is intended to aid doctors in identifying lung nodules detected via CT scans that are likely benign. That test used multiple-reaction monitoring mass spec to quantify the levels of 11 proteins in patient blood samples.
The Xpresys Lung 2 test measures only two proteins, both taken from the original panel of 11, and combines measurements of these proteins with clinical factors like nodule size, location, and morphology and patient age and smoking status. According to Luderer, the new test offers a significant improvement in performance over the original. He said it is able to identify benign lung nodules with an average negative predictive value of around 97 percent. The original test had performance ranging from around 88 percent to 99 percent, "but we were unable to get a lot of patients up into the higher 90 [percent range]," Luderer said.
The company developed the new test using data from a pair of prospective trials for the original Xpresys that indicated that two proteins were responsible for the majority of the signal.
"Furthermore, those proteins go in opposite directions when a person switches over [from likely benign to not likely benign]," Luderer said. "So we get some amplification simply by that biological fact."
The rationale for Xpresys is that by identifying nodules that are likely benign, physicians can more comfortably put patients on a regimen of watchful waiting. A noninvasive test like Xpresys is desirable due to the expense and significant risks of the invasive procedures currently used for determining lung cancer status, like fine needle aspiration and thoracotomies.
Indi launched the original Xpresys test in October 2013 out of its CLIA lab, but the test has posted only modest sales since then, with around 2,000 total tests sold. And some physicians have questioned how broadly useful the assay might be.
For instance, in an interview at the time of the test launch, Howard West, a thoracic oncologist at Seattle's Swedish Cancer Institute, raised doubts about the test's ultimate effectiveness in helping patients avoid unnecessary procedures.
The test's low positive predictive value could, in fact, lead to higher numbers of follow-up scans and invasive procedures, rather than fewer, he suggested. Given this possibility, he noted at the time, the test needs to be validated in a broader setting prospectively.
Indi has been quite clear that the Xpresys test is intended only to rule out the possibility of cancer, with indeterminate or positive results not to be taken as indicating that a nodule is cancerous.
Likewise, Peter Mazzone, a pulmonologist at Cleveland Clinic who has been involved in collecting samples for one of Indi's clinical trials, noted at the test's launch that it might realistically be applied only to a small proportion of the patients that technically fit within its use guidelines — a patient who is otherwise somewhat ill and may not do well with a biopsy, for instance.
In total, Mazzone estimated, less than 10 percent of his patients fit the criteria under which he would consider ordering the Xpresys test. At the time, Luderer said the company's business model would work with the sort of patient numbers Mazzone cited.
One hope for Indi is that the improved performance of the Xpresys Lung 2 test helps ease such concerns. The company is currently setting up new studies, including a registry study and a multi-site clinical utility study that will help better establish its usefulness.
The company is also working with Medicare to establish pricing. "They have a dossier from us that speaks to what others have paid for the test and the health economics model, which will allow [them] to work and play with the model," Luderer said, adding that the company is hoping for a decision on pricing before March.
The first version of Xpresys lists for $4,250, though it is unclear what average payment per test Indi received. The company secured reimbursement for the test from a number of private payors including UnitedHealthcare, MultiPlan, and preferred provider organizations FedMed, Fortified Provider Network, InterWest Health, Stratose, and Three Rivers Provider Network. It also obtained coverage for the test from the US Department of Defense and Department of Veterans Affairs. In all, more than 200 million lives were covered for the original Xpresys test.
While this coverage is based on the first generation test, Luderer said Indi does not expect it will have to be renegotiated for the Xpresys Lung 2 test as this test "represents a significantly improved version of Xpresys."
Luderer said that the company has stopped sales of the original test as it transitions to offering Xpresys Lung 2.
He added that, despite its smaller panel size, the second-generation test would continue to be run on a mass spec format. The Xpresys test marked something of a milestone for clinical mass spectrometry in that it was the first multiplexed proteomic test to go to market using MRM-MS on a triple quadrupole instrument.
Luderer noted, though, that the smaller panel size makes the test more amenable to an immunoassay format, something he said Indi might pursue in the future if it were to convert the test to an in vitro diagnostic kit and take it through the US Food and Drug Administration clearance process.
"It's not a trivial exercise but it's something that should be possible," he said.