NEW YORK (GenomeWeb) – Integrated Diagnostics is preparing to launch its second-generation Xpresys Lung test, a blood test to help assess whether lung nodules are likely benign or cancerous, in the second half of next year.
With Medicare coverage for the test in place, the company is hoping it will surpass the limited commercial success of its initial Xpresys Lung offering.
Indi is also submitting for publication results from its Panoptic study, a 33-center prospective trial of the test that CEO Albert Luderer said will support the company's commercialization efforts.
The Xpresys Lung 2 test is a refined version of Indi's original Xpresys test. Both are intended to aid doctors in identifying whether lung nodules detected via CT scans are likely benign, which could spare patients expensive and invasive procedures like fine needle aspiration and thoracotomies.
The original 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, patient age, and smoking status.
Indi launched the original Xpresys test in October 2013, out of its CLIA lab, but the test posted only modest sales, with around 2,000 total tests sold during the roughly three years the test was on the market. The company decided to pull the test from the market last year as it worked to develop the second-generation Xpresys diagnostic.
The original test was covered by a number of private payors, including UnitedHealthcare, MultiPlan, and preferred provider organizations FedMed, Fortified Provider Network, InterWest Health, Stratose, and Three Rivers Provider Network — a collection of insurers that comprised more than 200 million covered lives in total. The company was unable to secure CMS coverage for the original test, however, which proved to be a significant impediment.
"I think [securing CMS coverage] is the hardest thing to do in molecular diagnostics right now," Luderer said. "It's been a very difficult process to predict, and it's probably, I think, one of the single [biggest] reasons why investors are a little bit skittish about [diagnostic] companies that are trying to pioneer new stuff. It's just really difficult. I'd say the whole process took us probably a year and a half to get it through."
Based on data from the company's Panoptic study, CMS chose to cover the test for assessing patients 40 years and older with lung nodules between 8 mm and 30 mm who have a pre-test cancer risk of 50 percent or lower based on the Mayo Clinic Model for Solitary Pulmonary Nodules.
The Panoptic study looked at 178 subjects, 29 of whom had malignant lung nodules and 149 of whom had benign lung nodules. Among those with benign nodules, 42 underwent at least one invasive procedure to further assess the nodule. Of the 29 malignant nodules, 13 were moved on to surveillance, as opposed to biopsy or other procedures.
The study found that had the Xpresys 2 test been used to guide these patients' treatments, it would have reduced the number of benign patients receiving invasive procedures by 36 percent and reduced the number of malignant nodules passed on to surveillance to 3 percent.
The test demonstrated a sensitivity of 97 percent, specificity of 44 percent, negative predictive value of 98 percent, and positive predictive value of 25 percent in the study.
Part of the company's shift in thinking, which Luderer noted was reflected in the CMS approval, was to take a more narrow focus on moderate-to-low-risk patients.
"One of the observations was that physicians are pretty good at figuring out if a patient who presents with a nodule is more likely to have cancer than not," he said. "So they are pretty good at picking up high-risk patients, but not really good at sorting through the moderate-to-low-risk patients. Because there is so much fear that they will miss a cancer."
"So our position on this, and I think CMS also felt this way, is that if a patient has high risk, you shouldn't be playing around with trying to see if they are benign," he said.
The expression of the two proteins used in the new test move in opposite directions when a nodule is malignant, and analysis of data generated in studies of the original test indicated that this pair provided most of the test's diagnostic power, Luderer said. Adding clinical factors to expression levels of those proteins brought the median negative predictive value of the test to 98 percent, up from around 91 percent for the first-generation Xpresys test.
The original 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. Indi will continue running the test on a mass spec platform, even though the the two-protein panel could make it more amenable to an immunoassay format.
Luderer said that while the test only reports the levels of the two proteins, it actually measures a total of 24 proteins, which the company uses for quality control and to gather data for future product development. He said that Indi's future plans include possible expansions of its lung portfolio as well as moves into other areas of cancer and potentially some neurology applications.
The primary focus currently, though, will be commercialization of the Xpresys Lung 2 test. Luderer said the company is working to establish relationships with community hospitals that can anchor the launch of the test and establish clinical registries.
"We're going to be looking at major [community] centers that can help us to support an initial launch, and then from within each one of those major geographies that we select, we will radiate from those major centers and push our selling efforts," he said.
In recent years, large-scale studies, most notably the National Lung Screening Trial, have found that screening high-risk patients, like long-term smokers, using regular CT scans could reduce lung cancer mortality. This has led to expectations of increased CT scanning and a subsequent increase in the number of patients presenting with indeterminate lung nodules.
Luderer said, though, that Indi expects the bulk of demand for the Xpresys test to come from incidental findings in patients receiving a chest or lower abdominal CT for some other reason.
CT screening of high-risk patients is starting to take off, he said, but the number of potential Xpresys uses emerging from those programs is "dwarfed by the incidental findings that arise each year from just the normal course of patient evaluation."
An increase in patients due to CT screening programs would be "helpful," Luderer said. "But we don't have it modelled into our basic pro-forma, because it's hard to assess right now."
Luderer said that Indi has "had enough funding to keep going," in the year-plus since it pulled the original test from the market, but that "it has been a struggle." The company raised $6.1 million in Series C funding from Bird Capital and InterWest Partners at the beginning of 2017.
"We have had to get very small to bring our technology through," he said. He added that the company is currently working to line up new funding to drive the Xpresys Lung 2 commercialization effort and that he hopes to have this funding in place within the next several weeks.