In a move that further opens a new avenue to stent treatment as well as providing competition in the sector, Abbott (Abbott Park, Illinois) subsidiary Abbott Vascular Devices (Redwood City, California) last month reported receiving FDA approval for a new minimally invasive device to treat patients with carotid artery disease (CAD), a risk factor for stroke. Abbott re-ceived FDA approval for the Xact Carotid Stent and 510(k) clearance for the Emboshield Embolic Protection System to treat patients at risk of stroke who are not favorable candidates for surgery, i.e., high-risk patients.

Abbott becomes the second company to enter the U.S. carotid stent market, joining Guidant (Indian-apolis), which received a clearance from the FDA for its Rx Acculink carotid stent and Rx Accunet embolic protection system last September. The company beat out powerhouse Johnson & Johnson (J&J; New Bruns- wick, New Jersey) for the second-to-market honors, even though the Precise carotid stent, manufactured by J&J’s Cordis Endovascular (Warren, New Jersey) unit, was recommended for approval by the FDA's Circulatory Systems Devices panel in April 2004 and given a conditional approval last August. The Precise product has been in regulatory limbo since J&J received a warning letter from the FDA concerning the need for “corrective actions” related primarily to lapses in protocol for a trial of the Precise system.

The new Abbott system features a stent specifically designed to treat diseased carotid arteries – arteries in the neck that have become clogged or partially blocked due to the build-up of fatty plaque and debris, also known as atherosclerosis. The Xact stent is self-expanding and has a closed-cell design that creates a tightly knit yet highly flexible mesh intended to help restore the inner diameter of a carotid artery, promote a smooth inner vessel surface, and potentially reduce the release of emboli from a diseased vessel when it is treated, which can lead to stroke.

The Xact stent is designed for use in combination with the fully retractable Emboshield filter. Embo-shield is designed to capture emboli that can break off during a carotid stenting procedure. The goal of CAD treatment is to restore adequate blood flow in the region of the artery that is blocked and to stabilize the fatty plaque in order to prevent plaque rupture that can create embolic debris leading to a stroke. Patients with severe carotid blockages have traditionally been treated via the highly invasive carotid endarterectomy (CEA), a surgical procedure in which the artery is opened and the plaque is removed.

Geoff Yates, global marketing director for endovascular at Abbott, told Cardiovascular Device Update that the key difference between the Emboshield and other embolic protection devices on the market is Abbott’s use of what he calls Barewire technology. He said that since the wire floats freely in the Embo-shield, “the filter stays apposed to the vessel wall, [and] the wire moves freely, preventing any type of trauma or damage to the vessel.”

Yates said, “All the other devices on the market place are actually fixed to the wire.” He said with all the other embolic protection devices on the market, filter movement occurs during carotid artery stenting. “With Barewire technology, we eliminate that.”

Abbott established an exclusive agreement to market and distribute the system in February 2001 with Mednova (Galway, Ireland), which developed the stent and filter. Yates said that the Mednova agreement was a staged acquisition and that the FDA approval “triggers the finalization of the acquisition.” He noted that Abbott has already been distributing the products in the international market – primarily Europe and Australia – “for a number of years,” and has garnered a 10% market share in Europe alone.

The company received approval and clearance for its system based on the submission of SECuRITY Registry Study data in a premarket approval application filed in 2004. Both products have CE-mark approval and were launched in the European market at the end of 2003. The SECuRITY Registry Study was a prospective, multi-center, non-randomized trial involving 305 patients from 30 sites in the U.S. and Australia, designed to demonstrate the safety and effectiveness of the system in treating CAD.

In April, the company initiated a trial that, if successful, could greatly expand the patient population for carotid artery stenting. The ACT 1 (Asymptomatic Patients with Significant Extracranial Carotid Occlusive Disease Trial) trial is a multi-center, randomized study investigating the benefits of CAS vs. carotid artery surgery in the broader asymptomatic patient population. These are patients without symptoms of stroke who have CAD and who would otherwise be referred for surgery to treat their condition.

If Abbott’s new trial shows carotid stents to be as effective as traditional surgery in preventing stroke in lower-risk patients, it could potentially expand coverage for the procedure to a much larger population. An estimated 175,000 CEAs were performed in the U.S. in 2003, with another 100,000 procedures done in other countries.

Guidant has listed its combined stent and filter system for CAD at $3,500, and Yates said his company plans to be “competitive” with that figure.

Other firms developing distal protection devices and carotid stents include Boston Scientific (Natick, Massachusetts), with the FilterWire EZ and Carotid Wallstent; EndoTex Interventional Systems (Cupertino, California), with the NexStent; Medtronic (Minneapolis), with the PercuSurge balloon occlusion system; the Vascular Systems unit of B. Braun Medical (Melsungen, Germany); and Rubicon Medical (Salt Lake City), with the Rubicon Filter.

CABG Medical in trial relaunch in Europe

CABG Medical (Minneapolis) reported last month that it was able to relaunch enrollment in its European clinical trial of the Holly Graft System, a drug-eluting graft (DEG) for facilitating a coronary artery bypass procedure. The news came just over a month after the company called a halt to its CE-mark clinical trials for that device because the first two devices implanted (in Australia) became occluded. According to Manny Villafana, chairman and CEO of the company, CABG was able to get back in the saddle so quickly due to the relative simplicity of the corrections that needed to be made on the system in order for the trials to proceed.

“The concern that we had with the device was that the connection has to be made a certain way surgically,” he told CDU. After reviewing its preclinical work, the company said it believed that a “simple improvement in the surgical procedure” was necessary and that has been incorporated into its human cases. Essentially, surgeons will make a larger incision in the vena cava where it connects with the system’s flow limiter to ensure that the blood flow gets through to the vena cava. Prior to this decision, surgeons had been making a slit where the device connected. “We feel that the slit was closing down, which then impairs the function of the graft and causes the graft to close down,” Villafana said.

He also said the company has developed a new coating process to spray the heparin coating on the vessel connector. The spray heparin, he said, “allows for a more uniform and consistent application of the coating, which has demonstrated superior in vitro bench testing results and in vivo preclinical results.”

“All of the approvals that we needed overseas were based on the newer coating process because of our animal work and so we were ready to go,” Villafana said, adding that after the fixes were made, “Doctors came in, were trained in one week [and] they turned around and started doing implants.”

The Holly Graft System is designed to treat blockages in multiple coronary arteries from a single graft. The system consists of a flexible, thin-walled vascular graft made of expanded polytetrafluoroethylene; it is attached to the coronary arteries via connectors coated with a drug combination to reduce the risk of blockage and thrombosis. The major benefit of the system is to eliminate a secondary surgery conducted as part of a heart bypass procedure to harvest healthy vessels from the chest, legs or arms for use in the bypass, the company said.

In keeping with its historical policy on disclosure, CABG said it does not intend to provide press releases documenting individual human cases going forward. Villafana said that the company intends to release the first preliminary data from the European trial at the Pioneering Techniques in Cardiac Surgery meeting Dec. 1-2 in Leipzig, Germany. Because of the delays, Villafana said the company would have to postpone its investigational device exemption submission to the FDA from its projected late 2005-early 2006 estimate to at least the second half of 2006.

CABG Medical raised more than $30 million in an initial public offering of some 5.5 million shares late last year and subsequently added another $4.5 million through sale of an additional 825,000 in the exercise of over-allotment options.

SEC charges misinformation by Biopure

The Securities and Exchange Commission (SEC) in mid-September issued a complaint against Biopure (Cambridge, Massachusetts), charging that it failed to disclose and mischaracterized information concerning its primary product, Hemopure, “while at the same time ... raising millions of dollars from investors.” The charges add to the hurdles, legal and regulatory, faced by Biopure, and not unknown to the blood substitute/oxygen therapeutics companies which have had difficulty moving their products to commercialization. The SEC complaint adds to a variety of shareholder lawsuits charging misinformation by the company, as well as insider profit-taking.

Robert Buhlman of the Bingham McCutchen (New York/San Francisco) law firm, in a company statement said that Biopure would seek to dismiss the claims “and expects to prevail,” arguing that its disclosures to the SEC and the FDA were in complete compliance with current procedures and practices.

The SEC’s action was filed in U.S. District Court in Massachusetts, citing violations of federal anti-fraud rules by the company, a company executive and two former executives: Jane Kober, general counsel; Thomas Moore, former CEO; and Howard Richman, former senior vice president of regulatory affairs. According to the complaint, Moore “personally made and approved misleading statements”; Richman, “the former officer responsible for FDA relations, made and provided information for misleading statements”; and Kober “drafted and approved misleading statements.”

The complaint comes as no great surprise to Biopure, since it received an SEC Wells Notice concerning the possibility of receiving the complaint in late 2003. And Moore and Richman were removed from their positions in June 2004 in a sweeping restructuring of the company – along with the announcement of staff cuts and a shift in emphasis to cardiovascular applications.

The SEC charges that in April 2003 Biopure began receiving “negative information” from the FDA concerning its attempts to win approval for the Hemopure oxygen therapeutic “but failed to disclose the information, or falsely described it as positive developments.” That information included the FDA’s “clinical hold” on its clinical trials of the product in trauma settings because of safety concerns, but that over the next eight months it “concealed” this fact “while making public statements about its plans to obtain approval for trauma uses of Hemopure.”

In addition, the SEC charges that in July 2003 the FDA informed Biopure that it had not approved Biopure’s application for use of Hemopure in orthopedic surgery, and instead conveyed “serious concerns” about the reliability of its supporting data. “Biopure,” the complaint says, “issued public statements beginning on August 1, 2003, describing the FDA’s communication as good news, causing its stock price to increase by over 20%.” The SEC complaint went on to say that the company continued to make other misleading statements, up until December 2003, while raising more than $35 million in investments. Then, the “true status” of the product’s regulatory status was made public, with a resultant plunge in its stock price of nearly 66%.

In response to the SEC’s claim concerning the hold on its clinical trial for trauma patients, Biopure said the claim “confuses the safety of the product with the safety of [the] proposed clinical trial design.” The company acknowledged that it did not disclose the filing of the proposed protocol and that it “does not and did not view the data questions or the proposed trial itself to be material to an investment decision,” but rather that these communications with the FDA were part of “normal back-and-forth between the FDA and the clinical trial sponsors.” It added that the trial’s indication for in-hospital trauma was not in-tended for commercialization and that it “spent an insignificant amount on the proposed trial.”

The company said that the FDA designated the in-hospital trauma trial as a separate investigational new drug application from the firm’s then-pending biologics license application for a proposed orthopedic surgery indication. Biopure said it “intends to prove that the FDA questions were specific to the in-hospital trauma IND, and FDA was not addressing the status of the orthopedic surgery BLA in its communications about the IND.”

AAA product said to infringe

Shaun Samuels, MD, an interventional radiologist from Miami, has filed a complaint in U.S. District Court in Marshall, Texas, charging patent infringement, trade secret misappropriation and unfair competition by Boston Scientific.

The complaint alleges that the TriVascular Enovus AAA stent-endograft product made by TriVascular (Santa Rosa, California), a business unit of Boston Scientific, infringes Samuels’ U.S. patent No. 6,007,575, titled “Inflatable intraluminal stent and method for affixing same within the human body,” derived from Samuels’ technology.

The complaint further alleges that a key consultant and advisor of Boston Scientific/TriVascular was involved in the misappropriation of the proprietary information relating to plans for developing Samuels’ endovascular technology.

A former bioengineer, Samuels was a clinical assistant professor at Stanford University (Palo Alto, California) and was chief of interventional radiology at the VA Hospital in Palo Alto. Currently he is an interventional radiologist at an endovascular institute in Miami.

In the complaint, Samuels says that his first patent was issued in 1995 and that he holds 10 medical device patents, six of which are based on inflatable cuff technology, calling this a low-profile design that allows for minimally invasive entry and placement in the vascular system. Two of the inflatable cuff patents are directly related to abdominal aortic aneurysm (AAA) stent-graft designs.

An endograft is used interventionally to repair abdominal aortic aneurysms, a ballooning of the wall of the main artery of the body which, when it ruptures, frequently proves to be fatal. The Stanford Group (Houston) estimated that the market for AAA endografts could grow to $2.8 billion by 2010.

Samuels is represented in the action by John Sweeney and Harry Marcus of Morgan & Finnegan (New York); Mikal Watts and Martin Siegel of the Watts Law Firm (Houston); and Carl Roth and Michael Smith of the Roth Law Firm (Marshall, Texas).

Thoratec to acquire additional building

Thoratec (Pleasanton, California) reported signing an agreement to purchase a 67,000-square-foot office building in Pleasanton. The purchase price for the facility, located adjacent to the company’s current headquarters building, is about $13.4 million, subject to adjustments at closing.

The company said it would incur some capital expenditures for tenant improvements to the building over the next several years.

Thoratec employees, now working in a leased facility about a block away, are expected to begin moving into the building during 1Q06, allowing the current Pleasanton facility to be focused on expanded ventricular assist device manufacturing.