One To Watch: Check-Cap “X-ray sonar” could break through capsule endoscopy uptake barriers

After securing CE mark approval for its C-Scan capsule endoscopy technology in January, emerging Israeli company Check-Cap is about to embark on its US clinical journey with a pilot study slated for the end of this year. The firm is targeting the colorectal screening market, a market marked not only by the negligible presence of capsule endoscopy but also by the overall low screening adherence rates due to specific barriers of current techniques that Check-Cap believes C-Scan could overcome.

 

What’s happened

Check-Cap said on Thursday that it has received US FDA approval to initiate a pilot study of its C-Scan system, on condition that the firm submits additional information. The company declined to disclose details of the additional information which the regulator had requested, but it told FirstWord MedTech that it is "working on it" and does not anticipate it being an issue in starting the trial. It said its target is to start patient enrollment before the year is out.

 

The backstory

Colonoscopy remains the gold standard for colorectal screening, and its high sensitivity rate (between 90 percent and 98 percent) for detecting precancerous polyps makes it the preferred screening method over less invasive in vitro diagnostics like faecal occult blood test (FOBT, between 9 percent to 24 percent sensitivity for precancerous polyps) and faecal immunochemical test (FIT, between 32 percent and 53 percent sensitivity).

However, colonoscopy adherence rates are notoriously low worldwide, around 60 percent in the US and as low as 20 percent in Germany. This is due partly to patient concerns over the invasiveness of the procedure, but it appears the preparation - involving laxatives and fasting - a patient has to go through prior a colonoscopy makes up a sizeable barrier to colorectal screening, according to a 2007 survey by the Mayo Clinic.

 

The lowdown on C-Scan

Capsule endoscopy, pioneered by Given Imaging with its PillCam technology, could be considered a good minimally invasive alternative to colonoscopy for colon screening. Capsule endoscopy typically involves a patient ingesting a vitamin-sized pill containing a miniature video camera which captures images of the digestive tract as it travels through the system. These images are transmitted to a recorder worn on the patient’s body and the data then downloaded and compiled into a video for the physician to review.

But while capsule endoscopes may address the invasive nature of colonoscopy, this method does not eliminate the need for patients to do a laxative cleansing prior to ingestion of the capsule and also the need for the patient to take booster laxatives to eliminate the capsule from the body.

Alex Ovadia, CEO of Check-Cap, added that another key barrier to current capsule endoscopes being used for colorectal screening is that if there is something in the colon that obstructs the view, such as residual faecal matter, at least in a traditional colonoscopy the physician would be able to manipulate the colonoscope then and there to get a better view. With a video capsule, there is no way of manipulating the device to clear the obstruction as it works its way autonomously through the colon.

These limitations mean that capsule endoscopy for colorectal screening have not really taken off, whereas this modality has had more success in the small bowel, according to Ovadia. Indeed, while Given (now part of Medtronic) has developed three PillCams for both the small and large bowel, as well as the upper gastrointestinal tract, the other players in the capsule endoscopy market have limited their offerings to just the small bowel, such as Olympus Medical with Endocapsule 10, CapsoVision with CapsoCam Plus and Stratis Medical with MicroCam.

Check-Cap has designed its C-Scan system to be completely prep-free, without the need for any laxative cleansing prior to capsule ingestion nor the need for any boosters for elimination. This is down to the underlying X-ray technology used in the capsule to acquire images of the colon, which also overcomes the problem of obstructed view during tracking, a limitation of video imaging that is used in currently available capsule endoscopes.

 

Naval inspiration

The C-Scan Cap acts like "an X-ray sonar" that acquires intraluminal information from the colon, said Ovadia. "It can penetrate anything so the patient doesn’t need to have a colon cleansing and we don’t have a problem with residual stool in the colon obstructing the acquisition of images during the tracking procedure."

C-Scan is the brainchild of Check-Cap’s CTO Yoav Kimchy, who got his inspiration from his time as a naval officer. "Yoav was asking himself, if we are able to track submarines in the sea, why couldn’t we track a small submarine, ie a capsule endoscope, inside our body?" said Ovadia.

The C-Scan Cap is made up of a small X-ray source and X-ray detector panels connected to proprietary single photon counting electronics. The capsule is propelled through the gastrointestinal tract by natural motility, but there is a motor to rotate the X-ray source 360 degrees, forming three beams that scan as the capsule moves within the colon.

C-Scan Cap is swallowed together with a tablespoon of radiopaque contrast agents. No fasting or bowel preparation is required; the patients can continue with their daily activities and only need to ingest a small amount of contrast agent together with fibres with each meal, three times a day.

Once inside the colon, the X-ray photons emitted by the capsule interact with the ingested contrast agent that mixes with the colon contents. This interaction generates secondary X-ray fluorescence photons, some of which are back-scattered towards the capsule and are detected by the X-ray detectors.

Additionally, the emitted X-ray photons also undergo an inelastic interaction with electrons of atoms in the colon wall and lumen, a phenomenon known as Compton scattering. Some of the photons scattered by this mechanism head back in the direction of the capsule with an energy correlated to their angle of scatter.

These two interactions are measured separately using the capsules photon-counting electronics and the data provide information on the distance and position of the capsule in relation to the colon.

The data are transmitted from the capsule to the C-Scan Track, a patch-based tracking system that the patient wears on their lower back throughout the 2-3 days that the capsule works its way through the colon. When the capsule is passed out, the tracking system will set an alarm to alert the patient. The data recorded by C-Scan Track are then downloaded to a workstation. Check-Cap’s proprietary software C-Scan View processes the data and constructs the 2D and 3D maps of the inner surface of the colon.

 

What next

To date, more than 250 patients have ingested the C-Scan, and the company is in the midst of a post-CE mark study to build clinical evidence to back its technology. Check-Cap published interim results from this study in the third quarter this year, which showed that C-Scan had a sensitivity of 76 percent and specificity of 80 percent for detecting precancerous polyps. While Ovadia acknowledges that this does not match up to colonoscopy’s sensitivity rates, the clinical data for C-Scan so far show the technology can match up - and even be superior - to Given’s PillCam, which he said has shown 71 percent sensitivity for polyps measure 10mm and above and 64 percent sensitivity for smaller polyps of 6-9mm.   

As it embarks on its US regulatory pathway, Ovadia indicated the company intends to start commercialisation activities in Israel and the EU next year, pending more promising results from its post-CE mark study and sufficient funds.

While the C-Scan’s prep-free and user-friendly design is a compelling advantage that could, as Check-Cap has underlined, increase patient’s adherence to colorectal screening, everything boils down to data and the company would need to demonstrate clearly the value proposition of its technology. Check-Cap argues that by increasing screening adherence and patients’ willingness to undergo colonoscopy, more cases of potentially cancerous polyps can be detected earlier and less costly preventative measures can be taken, instead of more expensive treatments of later-stage cancer. The cost savings to the payer, in other words, come indirectly from the prevention of disease and rather than from the procedure itself.

This might require Check-Cap to work harder and take a longer time to build its health economics argument. Another snag is the absence of reimbursement codes for capsule endoscopy in large bowel screening and Ovadia said a new code would likely need to be generated for this indication.

That said, at least the company is looking to price C-Scan around the same ballpark as colonoscopy. "Our goal is to compete with colonoscopy so we are targeting a very similar cost to colonoscopy. The cost of C-Scan should be compelling enough for us to compete in that landscape," he told FirstWord MedTech.

 

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