Just as heart disease continues undiminished, so do the opportunities for mining new therapeutic sectors in the cardiovascular arena. Such an opportunity is being developed through the recent agreement between Percutaneous Valve Technologies (PVT; Fort Lee, New Jersey) and 3F Therapeutics (Lake Forest, California) designed to push forward an interventional approach to heart valve replacement and repair. As its name indicates, PVT's technology is a less-invasive method, employing a catheter strategy for valve delivery as opposed to the traditional, and highly invasive, open cardiopulmonary procedure. With the agreement, PVT will use a tissue valve developed by 3F, one that differs from the usual porcine product since it is equine-derived.

The first of the interventional procedures was reported in April by PVT at the cardiology department of Rouen Hospital (Rouen, France) by Alain Cribier, one of the founders of PVT. Stanton Rowe, president and CEO of the company, notes that the initial market is represented by the 300,000 valve replacements each year – a market of more than $800 million – with 60% of these being replacements of aortic valves where PVT is focused initially. The interventional approach should expand this market even further since it enables replacement of valves among those who could not undergo the open repair procedure because of their poor condition or their advanced age.

Both PVT and 3F have products only in clinical trials and see no clearances for at least two years down the road, but they obviously see early, pre-clearance collaboration as a large positive. Highlighting the benefits of the new agreement, Walter Cuevas, president and chief executive officer of 3F, provides a succinct summary of the partnership with PVT: "They have a great technology related to delivering a heart valve – we have a great heart valve. It makes the deal a good thing for both of us."

The surgical strategy for delivering the valve essentially requires a sort of "ship in the bottle" technique, Rowe told Cardiovascular Device Update. The valve is delivered to the heart by threading through the veins, and a balloon-expandable stent is deployed across the defective valve, holding it open and allowing for placement of the new valve. The defective valve does not have to be removed, thereby further enabling the interventional strategy. Done in the cath lab under fluoroscopic guidance, the entire procedure requires no general anesthesia, making it totally different from the highly invasive open procedure valve replacement, according to Rowe.

Cardiothoracic surgeon James Cox, chairman and CEO of the World Heart Foundation (Washington) supported the approach, saying that the combination of PVT and 3F technologies "would be a significant contribution, improving outcomes for many patients and lowering costs," and could even show the way to eliminating the need for cardiopulmonary bypass in valve repair altogether.

"It is the first percutaneously delivered heart valve," Rowe says. "There are at least 10 companies working on new mitral valve technologies. We're the only company focused on percutaneous aortic valve replacement." 3F's patented Aortic Bioprosthesis is currently in trials at 11 centers in Europe and the company recently received FDA approval for clinical trial launch in eight centers in the U.S.

While the companies also will be developing their products along separate trial tracks, Cuevas notes that the new agreements "permit us to start development that will utilize both technologies." Besides forming an agreement with 3F, PVT late last year inked a pact with VenPro (Irvine, California), focused on the replacement of failed venous valves in the legs, and combining VenPro's expertise in valves with PVT's delivery systems. 3F also has been busy developing other alliances. This past March it reported that all of its European heart valve centers have been trained to use an electronic clinical data-capture system designed and supported by Acumen (Minneapolis, Minnesota), a collaboration which 3F says is "intended to improve the expediency, analysis and reporting of the information recorded under the 3F Therapeutics study protocol to regulatory agencies in Europe and the U.S."

Ruling slows Guidant in coated stents

A federal court in mid-June issued a ruling that may present a critical barrier to Guidant (Indianapolis, Indiana) as it attempts to stay in the race to bring new coated stent technology to market. The court ruled invalid an agreement in which Guidant would distribute a drug-coated stent developed by Cook (Bloomington, Indiana), with a third player in the arrangement being Angiotech Pharmaceuticals (Vancouver, British Columbia), the supplier of the paclitaxel coating for the stent. When that agreement was announced, Boston Scientific (Natick, Massachusetts) immediately challenged it, since it and Cook had signed previous agreements with Angiotech which, Boston Scientific contends, prevents Cook from selling paclitaxel-coated medical products to whomever it wished.

Cook had asked the court for a summary judgment to dismiss Boston Scientific's complaint challenging the Cook-Guidant link-up. However, Judge Charles Kocoras of the U.S. District Court for the Northern District of Illinois denied the motion, ruling that the language in its original licensing agreement with Angiotech did not allow Cook to establish an agreement with a third-party such as Guidant to distribute a paclitaxel-coated stent. Cook said it is likely to appeal the ruling and Guidant said it will continue to back the arrangement between the companies as legitimate.

Guidant is clearly hurt the most if the decision is upheld, especially since it has suffered other recent setbacks. In March, it closed down its ACTION trial in Europe, evaluating a drug-eluting stent using actinomycin-D, as a result of high restenosis rate. And the court's ruling throws a cloud over its IDE application with the FDA to begin the DELIVER trial using Cook's paclitaxel-coated stent. Perhaps seeing problems down the road Guidant, as backup, earlier this year established a licensing agreement with Novartis (Basel, Switzerland) for the use of that company's experimental drug everolimus as a stent coating.

The court's decision in the licensing dispute is a clear negative for Guidant, said Larry Haimovitch, president of Haimovitch Medical Technology Consultants (Mill Valley, California). Guidant's future entry to this market could be "way, way off," he told CDU. Just as significantly, he projected a longer competition-free period in the sector for J&J – expected to win clearances next year – and less competition for those that come next.

Following last month's decision, Boston Scientific issued a statement saying that the court had found that Cook's agreements with Guidant were "a sham" and that it would seek a permanent injunction "prohibiting any activities under the Cook-Guidant agreements and any future attempts to circumvent the Angiotech agreement."

Guidant, however, continued to stand its ground, saying it believed the ruling was in error because "the Angiotech license explicitly comtemplates a range of strategic relationships to allow sales of the licensed product. We will define an organizational construct consistent with the court's ruling and the Angiotech license agreement that allows for the commercialization of paclitaxel-eluting stents." It praised Cook's work in this sector "based on Guidant components."

Hemosol releases 70 in restructuring

Blood substitute developer Hemosol (Toronto, Ontario) last month said it would release 70 employees, about 35% of its total workforce, as part of a restructuring that will result in a one-time, second-quarter charge of about C$1.5 million. The intent, Hemosol said, is to reduce costs from C$5 million per month to C$3 million per month while the company attempts to push forward various regulatory clearances for its lead product, the blood substitute Hemolink (hemoglobin raffimer).

The company also reported delays in its timelines for reporting data from two trials of Hemolink in patients undergoing coronary artery bypass grafting surgery, citing "administrative complexities" in running the trials concurrently. Jason Hogan, director of investor relations, cited "a lot of administrative and logistical burden at the [clinical] sites" and an inability to recruit patients as rapidly as projected. Hogan told CDU that Hemosol might make some additions in regulatory and clinical staff in order to speed up enrollment and maintain focus on its R&D activities.

The first of the slowed trials, designated HLK 213, uses Hemolink in primary CABG surgery. It has passed an interim safety review, and patient enrollment is continuing, the company said, projecting data reporting in the fourth quarter. The second delayed trial is a similar CABG study designated HLK 214 and involves patients undergoing a repeat procedure. The company said it will not meet the third-quarter reporting date originally set, and no new reporting date was projected. Hogan said that the reporting delays would result in a three- to six-month delay in winning clearance for Hemolink in the UK, but that approval is still expected by next year. He said that for U.S. approvals, the company would use trial data to develop a Phase III pivotal trial.

Despite the delays, the company said it is moving ahead with construction of its new manufacturing facilities, though the commissioning of one facility will be delayed in order to put company resources into the Hemolink trial effort.

Cardiovascular sourcebook now available

American Health Consultants, publisher of Cardiovascular Device Update, has released its newest medical technology sourcebook, Advances in Cardiovascular Technology: Emerging Markets for the 21st Century. The 156-page sourcebook looks at more than 150 companies developing new products in cardiovascular assessment and therapy – plus sections on therapies to treat atrial fibrillation and congestive heart failure – referencing the latest leading-edge products, with updates on clinical and regulatory milestones and commercial clearances.

As indicated by the book's title, its emphasis is on emerging rather than mature technologies being developed in this sector, technologies certain to influence many other advanced developments in medical devices, diagnostics and biologics, according to Don Long, managing editor, who oversaw development of the book. "Cardiovascular technology has driven and will continue to drive most other leading-edge medical R&D," Long said. "We attempt to provide a map of the sector's future, both near-term and also over a horizon that should indicate major directions in the next five to 10 years."

For ordering information, phone (404) 262-5476 or (800) 688-2421.

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