Medical Device Daily Associate

PARIS – While the primary focus for many clinicians here at the EuroPCR meeting has been on developing a better polymer coating for drug-eluting stents (see adjacent story), one company has been focused on developing a drug-eluting stent (DES) that has no polymer whatsoever in hopes of eliminating the problems associated with them.

That company is the Sorin Group (Milan, Italy), Europe’s largest cardiovascular device company. It has developed the Janus Carbostent, which uses a non-polymeric drug elution technology that is designed to only precisely elute the drug tacrolimus toward the targeted vessel wall where it is needed without any blood loss.

The company unveiled interim six-month results from its Jupiter II clinical trial at the meeting that compared the Janus stent to the company’s bare-metal Tecnic Carbostent.

Marie-Claude Morice, MD, head of cardiology at Institut Jacques Cartier (Massey, France) and principal investigator for the trial, reported the results at an early Friday session in the Palais de Congr s focused on the pros and cons of polymer-coated DES platforms.

She said the interim results provided a strong indication of an excellent clinical efficacy and a good safety profile for the Janus stent. “The six-month angiographic follow-ups are well under way, and I am very pleased with the current clinical and safety profile demonstrated in these interim six-month clinical data,” Morice said.

JUPITER II is an international multi-center, double-blind, randomized clinical trial designed to evaluate the safety and efficacy of the Janus DES in the treatment of coronary lesions in direct stenting procedures as compared to the bare-metal Tecnic stent.

By performing a direct stenting, the surgeon is able to avoid the need for pre-dilatation of a vessel prior to implantation, thus reducing the overall cost of the procedure.

A total of 332 patients were enrolled in 16 European centers and randomized to either Janus (166 patients) or Tecnic (166 patients). Enrollment was completed on Dec. 20, 2004.

The still-blinded interim six-month clinical data for the statistical analysis (102 patients in group A and 88 patients in group B) appear to highlight strong clinical efficacy for both groups.

The study reported an 11.8% of major adverse cardiac events (MACE) rate in group A, compared with 3.4% in group B, and a target lesion revascularization (TLR) rate of 11.8% in group A vs. 3.4% in group B.

The MACE rate in both groups consisted only of TLRs. A TLR is defined as the need for a repeat intervention – either a percutaneous transluminal coronary angioplasty or a coronary artery bypass grafting – at the site of the target lesion due to the recurrence of symptoms, and is one of the best indicators of the performance of the drug-eluting stent system.

Morice reported good results on the safety profile. In particular, she noted that “an unprecedented” 0% thrombosis rate, both sub-acute (within 30 days from the procedure) and long-term, has been reported for both Janus and Tecnic.

Further disclosure of the six-month clinical data is planned at the European Society of Cardiology (Sophia Antipolis, France) congress in Stockholm, Sweden, in September, and the complete six-month clinical and angiographic outcome will be presented during the Transcatheter Cardiovascular Therapeutics congress in Washington in October.

“The study results seen so far confirm the basic assumptions on which Janus’ innovative stent project was developed, namely the haemo-compatibility of the surfaces and the targeted drug release,” said Antonio Bartorelli, MD, of the Institute of Cardiology at the University of Milan (Milan, Italy) in his presentation during the same session. He is chairing the independent data safety monitoring board and the critical events committee of the Jupiter II study.

In a press conference prior to the announcement of the trial results, Morice explained how the stent is able to elute drugs without a polymer. She said tacrolimus – also known as FK 506 – is a well-known drug compound and is the active ingredient of two products from Astellas (formerly known as Fujisawa Pharmaceutical; Osaka, Japan), the immunosuppressant Prograf and Protopic, used in the treatment of atopic dermatitis.

The tacrolimus is contained inside sculptured reservoirs on the external surface of the stent, the one in contact with the vessel wall, so that there is no need for a polymeric coating, according to Sorin. Additionally, Morice noted that the amount of drug loaded into the sculptured reservoirs is “significantly higher” than in a polymeric film.

Another unique feature of the Janus Carbostent is what Sorin calls its Carbofilm coating technology, which is integrally coated onto the surface of the stent.

This feature, said Morice, gives the stent good performance in thrombo-resistance as well as helping to avoid the risk of thrombosis.

Also since the stent is smooth and has rounded angles, it provides excellent trackability, she said, so that it can be used more easily even in complex anatomical sites such as tracts of tortuous, rigid vessels, calcified plaques and protruding parts of stents previously inserted into the coronary artery. Since the stent surface is so smooth, its low friction with the vessel walls helps to eliminate the risk of damaging the walls themselves.

Morice noted perhaps one of the most important aspects of the polymer-free Janus: “Because there is no polymer, and no risk of damaging the polymer, which is the case with other devices, this stent can be very safely introduced into direct stenting without the risk of losing part of the drug in the application,” she said.

When questioned by Medical Device Daily, about the efficacy of tacrolimus, Morice acknowledged that the drug has had some problems in the past. “And . . . it’s true that tacrolimus does not have an excellent reputation at the moment because it failed in a previous trial.” However, she was quick to point out that the trial failure involved a different stent. She also said that the drug is only part of the equation.

Greg Cash, president of Sorin Group’s vascular therapy business unit, also defended the compound. He noted that it is in the same family of drugs as sirolimus, which is used on Johnson & Johnson’s (New Brunswick, New Jersey) Cypher stent.

“[Tacrolimus] is an immunosuppressant like sirolimus and a cytostatic drug. How it differs from sirolimus however, is [that] sirolimus tends to have a fairly strong action on endothelial cells, where this drug spares endothelial cells and targets smooth muscle cells, which may help add to the safety profile that you see associated with the Carbofilm and the targeted drug delivery.”

The Janus stent received its CE mark in October 2004 and was officially launched in 4Q04. Sorin said the device has now been implanted in more than 10,000 patients worldwide, except in the U.S.