The technology behind a new bioabsorbable drug-eluting stent (DES) licensed by four companies has received CE-mark approval, clearing two of the stents for sale in most European countries.

These innovative stents bring an alternative to the troubled DES market that saw a dramatic 23% drop in usage of drug-coated metal stents last year following alarming news of safety issues.

BioSensors International (Singapore/Newport Beach, California), which holds the license for three key features of the new stent, reported last week that its BioMatrix stent had received the long-awaited approval and said it would immediately launch sales in the approved markets, which include certain Asian, Middle Eastern and Latin American markets that also recognize the CE regulatory mark.

“Our growth potential in these markets is very strong,” said Yoh-Chie Lu, chairman/CEO at Biosensors, adding the positive clinical data supporting BioMatrix positions the new stent as a potential breakthrough product.

The BioSensors announcement, which came on Jan. 17, was upstaged the day before by Terumo (Tokyo), which said it received the CE mark for its Nobori stent built with the same s-scaffold design featuring a biodegradable polylactic acid polymer (PLA) that releases Biolimus A9, an anti-restenotic drug that has proven less aggressive than therapeutics eluted by current market-leading stents.

Terumo holds an exclusive license on the BioMatrix technology in Japan and non-exclusive rights elsewhere, excluding the U.S. Terumo Europe (Leuven, Belgium), which currently markets the Tsunami bare-metal stent (BMS) and the company’s Axxion DES, said it expects to launch sales in more than 20 countries during 1Q08.

As the year began, Xtent (Menlo Park, California) said it had submitted an application for its Custom NX drug-eluting stent to the European notified body designated for CE-mark approval (Medical Device Daily; Jan. 2, 2008) and said it expects to begin commercial launch in the second half of this year. The Custom NX is based on the BioMatrix technology, which Xtent has licensed from Biocompatibles.

Devax (Irvine, California) reported in mid-December that it had completed patient enrollment in the DIVERGE clinical trial evaluating its Axxess stent that licenses Biosensor’s drug and polymer for a proprietary self-expanding nitinol stent specifically engineered for the treatment of coronary and vascular bifurcation lesions (MDD; Dec. 14, 2007).

Bifurcation lesions are areas of atherosclerotic disease that occurs at a location where one large vessel divides into two smaller vessels and concerns an estimated 20% of all patients undergoing a stenting procedure worldwide.

Demand for drug-coated stents fell after researchers in September 2006 reported a link between the stents and potentially fatal clots.

While the FDA handed down an indecisive ruling saying that the benefit of drug-coated stents continues to outweigh the risk for patients who meet the criteria of the FDA-approved label, the two manufacturers that dominated the first-generation market were hit hard, with Boston Scientific (Natick, Massachusetts) reporting a 38% drop in sales while Johnson & Johnson (New Brunswick, New Jersey) reported a 44% drop for its Cordis (Miami Lakes, Florida) subsidiary.

Sales of DES were estimated to be a $5 billion market worldwide in 2006, the year that the market peaked.

That same year at the annual Transcatheter Cardiovascular Therapeutics conference in Washington, Biosensors reported encouraging one-year data on the safety of a new version of the bioabsorbable BioMatrix at the same time that sales continued to crumble for the DES giants. BioSensors followed up in May 2007 at EuroPCR in Barcelona with two-year results demonstrating lower major adverse cardiac events rates for its drug-eluting stent compared to BMS.

Lu hammered the point home, saying, “The use of a biodegradable polymer may provide a viable alternative In the opinion of some cardiologists to treat coronary artery disease in the face of safety concerns.”

The European regulatory approval was based on results from the STEALTH I trial (Stent Eluting A9 BioLimus Trial in Humans) and the results of the NOBORI clinical program.

The principal investigator for the BioSensors bioabsorbable platform is Eberhard Grube, MD, chief of angiology and cardiology at Siegburg Heart Center in Germany, who said results from the various BioMatrix clinical trials “have been consistently very positive and promising.”

Three-year follow-up data released at TCT 2007 continued to demonstrate superior results for BioMatrix for both safety and clinical efficacy with what Grube said were “excellent procedural performance and outcome characteristics.”

The NOBORI 1 clinical program reviewed by European authorities included a two-phase study called NOBORI CORE and NOBORI Pharmacokinetics both reporting overall restenosis rates as low as 0.5% and no late stent thrombosis recorded.

The stent developed by Terumo using BioSensors’ licensed drug and polymer includes a hydrophilic coating which the company says enhances deliverability and reduces arterial wall damage. Terumo licenses Biolimus A9, an analogue of sirolimus that is expected to show reduced tissue proliferation and is eluted from BioSensors’ bioresorbable polymer.

NOBORI 1 is a 360-patient, prospective 2:1 randomized trial evaluating Nobori head to head with Boston Scientific’s Taxus stent in 29 centers across Europe, Asia and Australia.

The Nobori stent showed a non-inferiority vs. Taxus Express and Taxus Libert , and even superiority in efficacy endpoints such as late loss with what were characterized as “exceptionally low frequency” of adverse cardiac events and no stent thrombosis up to one year into Phase I and nine months in Phase II of the trials.

NOBORI CORE is a non-randomized study that included 54 patients treated with the Nobori stent and 53 treated with Cordis’ Cypher stent. At nine-month follow-up, the restenosis rate for the Nobori stent was only 1.7% compared to 4.2% for Cypher, and late loss was 0.1 mm compared to 0.12 mm for Cypher. And evaluation of endothelial function revealed no abnormalities for patients receiving the Terumo stent while there was some evidence of dysfunction for the Cypher.

Terumo plans additional clinical activities with the Nobori stent as part of a comprehensive program to characterize the stent’s long-term safety and efficacy in a variety of patient populations. The program will enroll more than 5,000 patients in randomized trials and post-marketing registry in Europe, Asia, New Zealand and Africa.

Meanwhile Xtent said it is continuing its work with the FDA to fulfill requirements for approval of the CUSTOM IV pivotal trial in the U.S. The company filed for an investigational device exemption in September. The company and Biosensors are in the process of responding to questions from the agency, and the companies estimate a total of up to about 2,500 patients will be necessary to support FDA approval.