The screening of at-risk patients for Barrett’s esophagus, a precursor to esophageal cancer, has long been a goal for health systems. Currently, most patients with the condition remain undiagnosed, and more than 90% of individuals are identified after it has progressed into esophageal cancer via endoscopy, according to a 2018 paper in Digestive Diseases and Sciences.
This late diagnosis translates into a five-year survival rate of less than 15%, while those cases caught during the Barrett’s esophagus stage and treated with endoscopic resection and/or ablation have a five-year survival rate of more than 80%. Globally, esophageal cancer is the eighth most common cancer – and the sixth most deadly.
Now, New York-based micro-cap Pavmed Inc. has launched the first commercially available, DNA-based Barrett’s esophagus test via its Lucid Diagnostics Inc. majority-owned subsidiary. Currently, it is available as a laboratory-developed test, but the company plans in January to start a clinical trial to support an in vitro diagnostic (IVD) version that could be used more broadly.
There are already much larger, more established competitors in the Barrett’s esophagus screening space, but none have gained widespread traction, and some remain in clinical testing. For example, Dublin-based Medtronic plc inherited its Cytosponge from the acquisition of Covidien.
The new Lucid test is known as the Esoguard Esophageal DNA Test; it’s analyzed via Lucid’s Irvine, Calif.-based commercial diagnostic laboratory partner Researchdx Inc.
“It's similar to Cytosponge, in that is a cell collection device,” Shaun O’Neil, Pavmed’s chief commercial officer, explained to BioWorld MedTech. “It's different in that we don't need to wait for the actual capsule to dissolve. As soon as the device gets to the stomach, we can immediately inflate it. We can do our targeted cell sampling at the distal esophagus, which is where the cells change from heartburn. We can immediately invert it, so the sample that we collected is now protected as we remove it from the throat, especially from cells in the upper esophagus.
“What's most important, though, is in addition to our device, we have our Esoguard assay,” he continued. “So, Esoguard is an esophageal DNA test. It's a diagnostic assay based on next-generation sequencing that looks for two methylated biomarkers and reports binary results, so positive or negative for Barrett's esophagus in addition to finding dysplasia and esophageal adenocarcinoma.”
By contrast, Cytosponge is a swallowable sponge in a pill that is pulled back up the esophagus to capture cell samples that are analyzed for the protein biomarker Trefoil factor 3 (TTF3) and cytological analysis by a pathologist. The Cytosponge had to be redesigned after a recall due to problems with the sponge detaching; the new version was cleared by FDA in 2018 and it is currently marketed.
Similarly, Madison, Wis.-based Exact Sciences Corp. and partner Mayo Clinic have worked on several approaches to Barrett’s esophagus screening in testing, including another sponge capsule and an endoscopic brush that are both analyzed for a panel of DNA methylation markers.
In addition, Mayo Clinic researchers last spring presented at the Digestive Disease Week meeting on a noninvasive method based on electronic ‘nose’ device that analyzes patient exhaled breath for volatile organic compounds associated with Barrett's esophagus. It was found to be particularly useful among Barrett’s patients already on high-dose proton-pump inhibitors; the device is being tested on blinded samples.
Patients with frequent gastroesophageal reflux symptoms and/or use of acid-suppressant medications, such as proton-pump inhibitors, as well as nonsteroidal anti-inflammatory drug (NSAID) use, are at high risk. Older patients who are smokers, obese and/or have a family history of esophogeal cancer are also at higher risk.
Unlike the sponge-based devices, Esoguard incorporates a balloon-based collection device known as Esocheck. It is a swallowable capsule containing a small inflatable balloon that is attached via a thin catheter. Once in position, the balloon is inflated rapidly to swab the target sample for cells. Prior to removal, it is deflated, and the sample is covered to prevent contamination during removal.
Once a sample is obtained, it is subjected to bisulfite conversion and polymerase chain reaction amplification. Next-gen DNA sequencing then is applied to determine the methylation status of 31 sites on the Vimentin and CyclinA1 genes. An algorithm calculates the percent of DNA molecules in which a proportion of methylated sites on either gene have exceeded a predetermined threshold.
An NIH-backed study evaluating the Esoguard approach was published in Science Translational Medicine last year. In a study of 408 patients, it was found to have greater than 90% sensitivity and specificity. That bests the 80% sensitivity that has been reported for Medtronic’s Cytosponge, which also was found to have 92.4% specificity.
O’Neil is confident about success. “We obtained a CPT code from CMS [the Centers for Medicare and Medicaid Services] earlier this year. It'll go live in January, and we're working on coverage. We believe we have a better device – but most importantly, we’re the first DNA one.”
The IVD trial is slated to begin enrolling patients at the start of next year across more than 60 sites. It will have two arms: one for detection to confirm the test in patients with known Barrett’s esophagus, and the other for screening at-risk patients under the existing guidelines. The screening portion will start as early as January, while the detection portion will start later during the first or second quarter.
Pavmed was founded in 2014, with an eye toward identifying and accelerating to market products that address unmet needs. The company went public in 2016 with a $5.3 million IPO. Its market cap (NASDAQ:PAVM) remains around only about $43 million.
The company in-licensed Esocheck from Case Western Reserve University. This is its most advanced effort, but it has a decent portfolio, to include a minimally invasive carpal tunnel treatment device, an implantable, intraosseous vascular access device and antimicrobial, resorbable ear tubes.