the biopsies recommended for people with Barrett’s esophagus miss cancer and pre-cancerous tissue 50 percent of the time, according to data provided by Exact.
Exact’s proposed diagnostic would scan for relevant DNA biomarkers in a tissue sample collected by a brush during periodic endoscopies, which are already typically recommended for patients diagnosed with Barrett’s esophagus. “We think we can dramatically increase the sensitivity of surveillance with the use of molecular markers,” Ahlquist said.
The goal would be to treat or even prevent esophageal cancer through endoscopic procedures that remove the unhealthy tissue, zap it with radio frequency waves, or kill it by exposing it to freezing temperatures.
But if Barrett’s esophagus is a possible precursor to cancer, why not just obliterate that tissue as soon as it’s discovered? Wouldn’t that render Exact’s test moot? “I think there’s been legitimate debate on that,” Ahlquist said.
The reason why Exact and Mayo see value in a molecular diagnostic for esophageal cancer boils down to the endoscopic treatments for early-stage cancer and pre-cancerous lesions, which are “pretty effective,” but still can result in complications, Ahlquist said. “If it was perfectly safe and without any complications long term, that would be sort of almost a no-brainer. That’s not the case. It’s also expensive, and many endoscopists have not been trained in that.”
The goal, then, is to operate only on the people who would truly benefit from such a procedure, he added.
Similar to the pancreatic cancer diagnostic, Exact intends to first commercialize the test that analyzes samples from endoscopic brushing, and later it will seek approval for a test that would target a broader segment of patients. The latter test would involve swallowing a small sponge tethered to a string, pulling it back out, and analyzing the tissue collected by the sponge when it rubbed against the lining of the esophagus. Such a test could be conducted in a routine visit to the doctor’s office.
A potential pitfall for Exact’s first esophageal cancer test is its success will partly depend on patients getting screened for Barrett’s esophagus in the first place. For the most part, at-risk patients have not been following national screening guidelines, Exact said. Nevertheless, the company pegs the diagnostic product’s market opportunity at more than $500 million per year in the U.S.
A small feasibility study of a three-biomarker test identified early-stage esophageal cancer with 100 percent accuracy, and it correctly detected pre-cancerous lesions 81 percent of the time, Ahlquist said. Exact and Mayo are now prepping a 300-person clinical trial that will test both the endoscopic brushing and sponge-on-string approaches.
—Lung: Much of last week’s presentation on the planned lung cancer diagnostic products rehashed what was previously announced, but there were three new nuggets of information I found interesting.
First, Sam Hanash—a medical doctor who directs MD Anderson’s cancer detection and treatment institute—gave some color about his organization’s process for selecting the biomarkers most likely to signal lung cancer. The effort has included poring over more than 1,500 medical papers on the subject. It has also involved analyzing blood samples collected from lung cancer patients at different times, including three to five years before diagnosis, six to 18 months before diagnosis, and at the time of diagnosis.
Second, Hanash shared early data from a panel of three biomarkers that correctly identified lung cancer in smokers 65 percent of the time, with a false positive rate of 5 percent. Although that’s not a very sensitive test, the false positive rate is better than CT scans, the current standard screening method. Exact and MD Anderson plan to do a lot more work to improve the panel of biomarkers that would be used in the diagnostic products, with a goal of reaching 90 percent in both sensitivity and specificity.
Finally, once the screening test is ready for prime time, the clinical trial could involve 15,000 patients or more, according to a slide during Thursday’s presentation. That would be even larger than Exact’s massive 10,000-patient trial that led to Cologuard’s approval. “This is not going to be a small clinical trial,” Conroy said. “It’s going to be at least one large clinical trial, potentially two clinical trials.”
