Check-Cap auditions for its screen debut

Check-Cap has a new spin on capsule endoscopy, using X-rays instead of a visual camera. But more compelling clinical data will be necessary if it is to position its device as a first-line screen.

Use of a swallowed capsule to help diagnose colon cancer was pioneered by Given Imaging, whose PillCam device was CE marked in 2006 and cleared by the FDA in 2014. Given achieved the aim of many medtech startups in 2013, when it was acquired by Covidien for $860m. Fellow Israeli group Check-Cap has already attained one of these goals and hopes to hit at least one of the others. But where PillCam used a visual camera, Check-Cap’s C-Scan devices uses X-rays. 

“The technology includes three main elements,” Alex Ovadia, Check-Cap’s chief executive, tells Vantage. “One is the ingestible X-ray capsule. The second is the tracking and recording system. And the third one is the proprietary workstation that allows the physician to perform diagnostics.” The tech is interesting enough, but Check-Cap faces near-term challenges, namely how to fund the next R&D steps. 

To get the device to market in the US Check-Cap will have to run a pivotal US trial in around 800 patients. But the company had just $18m in cash at the end of September, which will only last a couple of years at current burn rates. 

This might not be long enough to take it through to US launch. “I assume it would take probably a year to run this study in the US in numerous sites – maybe not only the US – and following that it would take some time to get the approval,” Mr Ovadia says. “So I would imagine that commercialisation in the US would not start before 2021.”

There are several ways for the group to refill its coffers, of course, but it will have difficulty raising cash on the capital markets. It went public in 2015, raising $12m at $6 per share, but has had a turbulent time on the Nasdaq; in April it performed a 1-for-12 reverse stock split, meaning that effectively, to date, its shares have declined 97% since the IPO. A $17.5m secondary offering in May, held at a 38% discount, did not help either. 

Partnerships

And money is not coming in from Europe. The company is not yet actively selling the device here despite obtaining CE mark in January, instead pursuing both a postmarket European trial and a pilot study in the US

Partnerships look like Check-Cap's only hope. It is seeking “partnership in Europe, Israel, and then hopefully the US as well,” says Mr Ovadia. “By next year we anticipate starting commercialisation in Europe, and that cannot happen before having a decent partner in Europe, and capital as well.”

There is one reason to be cheerful. Check-Cap has an alliance with GE Healthcare for manufacturing, making the devices to be used in the US pilot trial and helping to conduct the study; GE was also one of Check-Cap’s venture backers.

Check-Cap’s ability to attract collaborators naturally depends on the performance of its device.

C-Scan works by sequentially imaging slices of the internal lumen of the colon to show the structure, including any anomalies such as protrusions or a polyps. It transmits data to a tracker device the patient wears on their back, which records the capsule’s position when it takes the X-rays, allowing the system to piece together the internal structure of the organ and detect any cancerous lesions or precancerous polyps. 

The advantage of an X-ray-based device over visual technologies including PillCam and colonoscopy itself is that the preparatory bowel cleansing steps are not necessary. “We understand that the main barrier preventing people going for colorectal cancer screening is the preparation,” says Mr Ovadia. 

The data released so far, however, might be too early to allow a fair assessment of C-Scan’s ability to diagnose cancer. Interim data from 31 evaluable patients in the post-CE mark trial showed sensitivity of 76% and specificity of 80% for polyp detection, but this is not the same as detecting cancer. 

Colonoscopy can detect colon cancer with percentage sensitivity and specificity in the high 90s. This compares to ballpark figures of 85% sensitivity and 90% specificity for virtual colonoscopy, a specialised kind of CT scan, Mr Ovadia says, and up to 89% sensitivity and 89% specificity with the current version of PillCam, according to published data

And pivotal US data on Exact Sciences’ Cologuard, the market leader in noninvasive colon cancer testing, puts sensitivity and specificity at 92% and 87% respectively for cancer (Colorectal screening set to become a slightly less inexact science, March 28, 2014). For polyp detection, a measure more comparable to Check-Cap’s data, detection rates were 69% for polyps with high-grade dysplasia and 42% for serrated sessile polyps 1cm or more in size.

Exact’s test is perhaps the greatest competitive threat to Check-Cap if the company is right about patients wishing to avoid the prep steps required by visual imaging. The question is whether the polyp detection rates seen with C-Scan translates into sufficiently high cancer detection rates.

This is particularly true since the company is targeting the first-line screening setting. Check-Cap will initially chase the same patient population as PillCam, namely patients who cannot or will not undergo colonoscopy, but Mr Ovadia says that the eventual aim is to “compete with colonoscopy and make it compelling enough so that payers and physicians would refer this procedure to the entire population.”

Check-Cap's next step is its US pilot study, which has just received FDA buy-in in the shape of an investigative device exemption, and is now enrolling 45 people aged 40-80 at average risk of colorectal cancer. Should the capsule prove safe when the trial reports in late summer, the pivotal US trial should start by the end of 2019.

But it is not yet clear that C-Scan’s accuracy is good enough, or that its no-preparation angle is appealing enough, to persuade doctors and payers – or, more immediately, a partner.

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