NEW YORK – A new test and cell collection device being rolled out by Lucid Diagnostics aims to significantly impact screening for esophageal cancer and its precursors, eliminating unnecessary endoscopies for some patients while identifying those who need further monitoring and treatment.
Previously, an endoscopy was the only way to check for precancerous or cancerous cells in the esophagus. But Lucid Diagnostics' new EsoGuard Esophageal DNA Test, working in tandem with its EsoCheck Esophageal Cell Collection Device, has recently been put on the market to improve noninvasive screening options for the conditions that occur before esophageal adenocarcinoma (EAC).
Patients with gastroesophageal reflux disease (GERD) are at risk of getting Barrett's esophagus (BE), a benign metaplasia in the lower esophageal lining. Without monitoring or treatment, BE can turn into dysplasia and EAC, incidences of which have quadrupled in the past 30 years, according to data published in CA: A Cancer Journal for Clinicians.
Dysplasia can be treated with ablation, but most patients with EAC have it caught at an advanced stage, said Lishan Aklog, CEO of PavMed, the parent company of Lucid Diagnostics, and executive chairman of Lucid. The EsoCheck and EsoGuard, both licensed from Case Western Reserve University, are meant to enhance screening and help clinicians catch BE and dysplasia while it's still early enough to be treated and eliminated. Enhancing screening, in this case, means providing better sampling of the esophagus as well as a highly accurate test to determine whether precursor conditions have occurred, Aklog said.
For the sampling, Lucid Diagnostics offers the EsoCheck, which can be used to screen for BE in a five-minute office procedure. The device consists of a pill-shaped capsule containing a ridged balloon on the end of a silicon catheter string, which the patient swallows. Once the capsule reaches the stomach, the balloon inflates, and as the clinician pulls the capsule back up through the patient's esophagus, the ridges catch cells from the lower esophagus where Barrett's is found.
Once the cells are collected, the balloon folds back into the capsule, ensuring only the lower esophageal cells are captured. Aklog called the deflation of the balloon the device's "key feature," since it limits the number of cells included in the sample. The system is accurate and more impactful "specifically because you can do a targeted sample, and because it can be used on samples collected with a noninvasive tool," Aklog said.
Medtronic also has a cell collection device for the esophagus called the Cytosponge that it has commercialized, but the sampling is less targeted. The Cytosponge works in a similar way to the EsoCheck, but the Cytosponge balloon that scrapes squamous cells also captures cells from the upper esophagus and mouth, which can dilute the sample and make it harder to determine a result, Aklog said. The device is also less abrasive than the Cytosponge, said Amitabh Chak, a gastroenterologist at University Hospitals Cleveland Medical Center and professor at CWRU who worked on a study published in Science Translational Medicine testing the technology. Funds for the study were provided to CWRU and the Case Comprehensive Cancer Center from the National Institutes of Health, Chak said.
Avoiding the dilution is a selling point of the device, since capturing unnecessary cells decreases the ability to detect the needed signal, Chak said. It's like "looking for a needle in a haystack," he added.
After the cells have been collected, clinicians send them to PacificDx, a CLIA lab in Irvine, California, that performs the automatable EsoGuard test, which uses biomarkers from the vimentin and cyclinA1 genes that were licensed from Case Western. Using next-generation sequencing, PCR amplification, and bisulfite conversion, the test determines the methylation status of 31 sites in the genes, which signal BE. A bioinformatic algorithm then calculates the percentage of DNA molecules where proportions of methylated sites on either gene exceed specific thresholds.
The test determines a positive or negative result, with a positive result signifying the presence of BE or a more advanced condition, resulting in a patient being placed in a monitoring program with regular endoscopies or receiving ablation treatment.
The STM study found that the test had nearly 90 percent sensitivity and specificity at detecting BE and more advanced conditions. The pilot study tested 50 cases of different stages of BE, along with 36 controls.
Chak said he sees no downsides with the EsoGuard, and that "it's like doing a Pap smear of your esophagus." The only issues Chak said he could see are with patients who have difficulty swallowing pills or who have particularly strong gag reflexes.
The EsoCheck device received 510(k) clearance from the US Food and Drug Administration in June 2019, and the EsoGuard was commercialized as a laboratory-developed test in December. The EsoGuard and EsoCheck also received breakthrough device designations from the FDA.
Interpace Biosciences also has a test for esophageal cancer, the BarreGen, but it's a risk classifier that predicts which patients with BE will progress to esophageal cancer, and unlike EsoGuard it's for use on patients who have already been diagnosed with BE, Chak said. There have also been attempts to use breath testing for esophageal cancer, but he said those methods haven't been nearly as accurate.
Aklog said the company is seeking full in vitro diagnostic registration for the EsoGuard using samples collected by EsoCheck, and there has already been a pre-submission meeting with the FDA. As a result, Lucid Diagnostics has launched two clinical studies to support a premarket approval submission with 60 sites. One trial will screen high-risk patients without a prior diagnosis to measure the EsoGuard's performance against a standard endoscopy, and the other is a case-control study of the test on patients who already have the condition. Both trials are expected to be fully enrolled in the next 18 to 24 months, with a premarket approval submission expected to follow, Aklog said.
Although the EsoCheck was specifically cleared for use with the EsoGuard, Aklog mentioned there could be other indications for the device in the future, such as other inflammatory esophageal conditions.
The device and assay are specifically being marketed to gastroenterologists and primary care physicians in the US for patients with GERD and three out of six risk factors, including race, gender, and family history, according to guidelines from the American College of Gastroenterology.
There have been inquiries from Europe and Asia about commercializing the test, and Aklog said the company expects to expand EsoCheck and EsoGuard internationally in the "not-too-distant future."
Lucid Diagnostics is in active conversations with the Center for Medicare and Medicaid Services and Medicare Administrative Contractors about pricing and reimbursement, and Aklog said a coverage determination is expected this year. EsoGuard received a CPT code from the American Medical Association last year, so clinicians can bill the procedure under the specific code and seek reimbursement on a case-by-case basis, Aklog further noted.
Although Aklog wouldn't specify exact pricing or reimbursement, he said regular endoscopies start at around $3,000, and the EsoGuard is expected to be cheaper – which could be a major selling point for payors. Patients are often deterred from getting endoscopies because of the cost and discomfort associated, Chak said, and it's not feasible to perform an invasive procedure on all 50-year-old white men with acid reflux, who are a high-risk group of patients.
Aklog also wouldn't estimate the revenue expected from the device and assay, only saying that this is a "multi-billion-dollar market opportunity." He noted there's been less pushback from gastroenterologists and other clinicians than expected, especially since the point of the EsoGuard is not to cut down on endoscopies, but rather reduce unnecessarily invasive endoscopies for patients who don't need them.
"We thought we'd have to make a little bit more effort to make the case that this is not going to cut back on their endoscopy business, but actually increase it by increasing the overall activity in this space," Aklog said.
Another key selling point is that the EsoCheck itself isn't being sold at all. The company is stocking the device at centers with clinicians who have been trained to use it, and the reimbursement will come entirely from the EsoGuard assay at this point, Aklog said. He declined to provide specific numbers on how many sites have been trained to use the device, but said the response "has been enthusiastic and physicians are being signed up for training and clinical use at an impressive clip."
Detecting these conditions isn't the only aspect of the process Lucid Diagnostics has an interest in, however. Aklog mentioned that the company has also licensed progression biomarkers from Case Western and Fred Hutchinson Cancer Research Center to develop additional assays to measure and monitor progression from BE to dysplasia to EAC.
PavMed also has a therapeutic in the works, the EsoCure, which is a disposable ablation device for patients with dysplastic BE. The EsoCure isn't under the Lucid Diagnostics name, since it's a therapeutic and not a diagnostic. Aklog said he expects the company to submit the EsoCure to the FDA in 2021.
Lucid Diagnostics also announced today it has entered into a clinical trial research agreement with the University of Pennsylvania to determine the EsoCheck's effectiveness in patients with eosinophilic esophagitis, an inflammatory condition of the esophagus similar to inflammatory bowel disease.