VIENNA, Austria — In the second year of full-blown competition for a capsule camera market it created in 2001 and enjoyed exclusively until 2006, Given Imaging (Yokneam, Israel) continues to roll out clinical trials hitting where its newly arrived competitors can not reach.

A small study using the capsule for diagnosis of the small bowel, PillCam SB, was given maximum exposure during the meeting of United European Gastroenterology Week (UEGW) here as it scored a high specificity for spotting a rare cancer, expanding the potential indications for use of the capsule as a screening tool.

Jean Christophe Saurin from the gastroenterology group at the Hospices Civils de Lyon, part of the sprawling complex of the Centre Hospitalier Lyon in France, presented a 36-patient trial comparing Given's PillCam SB against computer tomography (CT) scanning for neoplasia, or early-stage cancer development, of small bowel adenocarcinoma.

All patients had a genetic mutation indicating susceptibility to Lynch syndrome with a risk 100 times greater than the general population of developing cancer, usually diagnosed between the age of 39 and 49 years at a late stage.

"Capsule endoscopy showed highly relevant images in three cases, or 8.3%, of lesions for two low-grade adenomas and one adenocarcinoma, which were histologically confirmed after surgery," Saurin reported. Only the larger-scale carcinoma was identified by the CT.

"The excellent tolerance of capsule endoscopy allows a very acceptable screening method," he said in an abstract presented to the almost 12,000 gastroenterologists attending, adding that a larger study could determine patient stratification to establish guidance for surveillance.

Saurin told Medical Device Daily the first version of the PillCam SB was used for the first 10 cases and the SB2 after that, but, "I am sure that the case of confirmed carcinoma was found with an SB1 capsule."

The first PillCam SB was upgraded in late 2006 in Europe, and in May 2007 in the U.S., to the second-generation SB2 featuring adjustable lighting and a triple layer optic with a view expanded to 156 degrees.

Comparing the modest imaging modality of a capsule tumbling in the murky depths of the bowel against the mighty machinery and advanced imagery of CT seems courageous.

It also was lucky for Given Imaging, as just one frame among tens of thousands for each of the two patients showed the lesion indicating the adenomas, literally saving the lives of these patients.

Saurin said that the clinical team in Lyon has developed a significant experience for small bowel cancer detection since 1990, using a CT-based technique where the small bowel is filled with water so that tumors become visible under the scan.

Results of this novel technique were published in 2006, he said. "The CT work is done on symptomatic patients, people who have tumors, and lots of them. Here we were after neoplasia, the most difficult to detect, even with CT."

It is not the size but the significance of this first study for Lynch disease that is paramount for Given Imaging and won UEGW's endorsement with a highlight in the opening plenary session for the event and a full-page article in the daily newspaper published for participants.

Given Imaging presented two other studies, one demonstrating effectiveness in disease management for children with small intestinal disorders and another as an early diagnostic tool among adults with overt obscure gastrointestinal bleeding.

But it was the smaller cancer study that claimed attention.

"Everything to do with cancer is important and a very emotional area of diagnosis," said Michael Häfer who manages clinical trials, regulatory affairs and quality for Given Imaging Europe, Middle East and Africa (EMEA) out of Hamburg, Germany.

Häfer said after 18 months on the market the SB2 has completely replaced the original SB capsule, which has been discontinued by Given Imaging, and is sold at the same price point.

Where there is consistent reimbursement in the U.S. for the capsule camera in small-bowel diagnosis with most insurers, there is effectively no reimbursement in Europe.

"We applied in France in 2006, for example," said Häfer. "In Scandinavia the payment is sometimes provided through hospital coverage, while in the UK, we have guidance from the National Institute for Clinical Excellence (NICE) but this does not immediately help because it does not assure an automatic adoption.

"We continue to work closely with key opinion leaders to win adoption," he said, explaining the strategic importance for Given Imaging of waves of clinical studies planned, adding that 2009 is "completely booked with new studies."

Häfer said there are about 1,000 PillCam SB systems placed in the U.S. and "I know that in EMEA there are almost 2,000 systems in place and they represent nearly 100% of sales."

Despite the lack of reimbursement, PillCam SB "is now mainstream, the gold standard in Europe for the diagnosis of small-bowel diseases," he said.

Given Imaging said it has sold more than 730,000 capsules worldwide and Millennium Research estimates the global market will grow to $180 million in sales in the U.S. by 2009 (MDD, June 3, 2008).

Olympus (Tokyo), which dominates the endoscopy market with a 70% share worth $1.34 billion, entered the European capsule camera market with its EndoCapsule in October 2006 and the U.S. market one year later.

Where the Given Imaging SB2 capsule must be retrieved manually by the patient after its passage through the digestive tract in order to play back the recorded images, the EndoCapsule uniquely offers real-time observation of images with radio frequency transmission at two frames per second.

The advantage of real-time transmission is problematic, as a gastroenterologist would need to sit with the patient for eight to 12 hours as the pill passed through the digestive tract to take advantage of this feature.

Sold for upwards of $750, the EndoCapsule provides higher-resolution images as well.

"I can only say we are clearly the market leader in the small-bowel market and that if Olympus is entering the competition, it means that we are here to stay," said Häfer.

"Olympus is an endoscope company and is not focused on capsules," he said, adding he would "be surprised if they are above 10% of the market share."

Another competitor challenging the Israeli company's dominance is what Häfer called, "that Korean company."

Sun Shin, international marketing manager for IntroMedic (Seoul, South Korea), smiled when he heard the reference, but took exception to the inference that Olympus may be distracted with a principal focus on endoscopes.

"Olympus has a dominant position in endoscopy with a very strong sales force, so their potential will also be strong if they decide to focus on this system," he said.

Shin estimated that Olympus holds a little less than a 10% share with its system placements after two years in the market and "a much lower share than that for actual use of their capsule.

"There is a lot of dust on Olympus systems sitting in clinics because they give away the units to win the placement," he said.

The sale of an IntroMedic system, or the decision to give it away to win the installation at a clinic, is entirely the choice of distributors in each market, said Shin.

"Last year when we launched at UEGW in Paris, we had one distributor and today we have 41 worldwide, with half in EMEA and the rest in Southeast Asia," he said, adding the company is now expanding into South America (MDD, Nov. 6, 2007).

Another change in the past year, Shin said, is a change in terminology for the company's unique system for transmitting the images from the capsule to a recording unit worn on the patient's waist during the transit of the digestive tract.

"After entering the American market we stopped calling it an e-field signaling and started calling it the human body communications system," he said.

The MicroCam capsule sends a low-power signal through body fluids that then passes through tissues riding on the natural electrical current covering the human body.

This gives a longer battery life of "11 hours minimum," according to Shin, and a decided clinical advantage.

"If you look at the studies, you see that in 20% to 25% of all cases the Given capsule stops taking images after eight hours before it reaches the ilio cecal," located between the small and large intestine.

"There is a lot of histology to study there," he said, creating an awkward situation for physicians in Europe where there is no reimbursement.

"The patient needs to pay out of pocket, let us say €1,000 ($1,280) and if the physician did not see what is going on in the end run of the capsule he either needs to tell the patient the procedure must be repeated," he said, or else remain quiet and hope there is nothing significant there.

The MicroCam features six LEDs with auto-adjustment of lighting, and as for optics, "it is different but I really am not willing to discuss it," said Shin, "except to say that we provide 320 pixel x 320 pixel images and Given Imaging provides one at 258 pixels x 258 pixels."

Significantly, the MicroCam captures three frames per second compared to the two per second for both the Olympus and Given Imaging capsules.

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