Abiomed (Danvers, Massachusetts) last month submitted to the FDA an application for market approval of its AbioCor implantable replacement heart under a Humanitarian Device Exemption (HDE). Approval under an HDE would make the AbioCor commercially available to treat a defined subset of not more than 4,000 irreversible end-stage heart failure patients. The company also is continuing the initial clinical trial for the AbioCor being conducted under an investigational device exemption (IDE) granted by the FDA. Fourteen out of the initial 15 patients have been enrolled in the trial thus far.

However, Abiomed said it is not required to enroll a 15th patient before submitting for approval under an HDE, since completion of the initial clinical trial is not a prerequisite for such a submission. The company has been involved in a lengthy IDE study – which began with the first AbioCor implant in Robert Tools at Jewish Hospital (Louisville, Kentucky) on July 3, 2001 – in order to gain premarket approval for a destination therapy indication from the FDA, which could potentially have opened the product up to an even larger patient population.

Michael Minogue, president and CEO, said an HDE approval will likely be the endgame for the first generation of the AbioCor. "I think the HDE is a huge accomplishment and is likely what we're looking for as the final result on the AbioCor I," Minogue told Cardiovascular Device Update. He said the 4,000 destination therapy patient figure granted under the HDE designation is four to six times "what the likelihood of today's population is [for] what's being used," and added: "We still have the capability of selling the number that we want to sell outside of the U.S., where cardiovascular disease also is the No. 1 killer."

Minogue said that once the company gets to the AbioCor II, which it will begin implanting in animals this year, "then you have the capability of a larger-scale ramp-up." The newer iteration of the device will be 35% smaller and is projected to be a five-year device vs. the two years projected for the original system.

In September 2003, Abiomed received approval from the FDA to designate the AbioCor as an HUD, a mandatory step preliminary to filing for an HDE. At the time of that designation, the company said it hoped to receive an HDE in the second half of 2004. At the time of the HUD designation, Ed Berger, PhD, vice president of strategic policy and planning, noted that as with the receipt of a PMA, the HDE would provide for the commercialization of the AbioCor heart, but noted two key differences. An HDE restricts use of the device to the patient population defined by the HUD. And secondly, rather than meeting the PMA standards of safety and efficacy for a broad patient population, Berger said that what must be demonstrated for an HDE is the device's "safety and the likelihood that [its] benefits will outweigh the risks." HDE applications also often receive expedited review when a device such as the AbioCor addresses a life-threatening condition and there are no other available options for treatment, the company said.

Minogue emphasized that the AbioCor isn't the only product the company has in its arsenal. In fact, he said Abiomed's priorities have shifted. "Our main focus now is to recover patients so that they can go home without anything." He said the company sells such bridge-to-recovery products as the BVS biventricular support system and the AB5000 circulatory support system. "I think one of the biggest opportunities that people have overlooked is the recovery market alone," he added.

Memry funds joint coated-stent effort

Drug-eluting stent (DES) technologies for use in the coronary arteries provide a clear and direct path to similar coated-stent use in the peripheral vasculature, and that is a wave that Memry (Bethel, Connecticut) says it refuses to miss. Memry, known for its "shape memory" alloy technology, reported in late August that it would provide $200,000 in funding to Biomer Technology (Runcorn, UK), a developer of polymers and biocompatible coatings. The goal is a joint development effort to create coatings for peripheral stents using Memry's nitinol stent platform. And Memry is investing an additional $400,000 to acquire a stake in Biomer.

While only two DES systems have been commercially cleared in the U.S. thus far, the developmental pipelines of several companies are filling up quickly, James Binch, Memry's president and CEO, acknowledged. But, he said, "From our perspective, the first coronary drug-eluting stent technologies are nothing but the first. They are by no means elegant, and they are by no means the final answer," he told CDU, "but they're a step in the right direction." As an indicator of the likelihood of rapid evolution and commercialization of advanced products in DES and other coated-device technology, he pointed to Boston Scientific's (Natick, Massachusetts) Taxus product "rolling over the Cypher," the first-in-class DES product from Cordis (Miami Lakes, Florida), calling that success "a case in point."

Binch said Memry has been looking at the potential for coated-stent opportunities "investigationally for 2-1/2 years" and talking with Biomer for the past six months. "We found that the technology they have developed represents the next major step forward," he said. "One of the things that attracted us to Biomer is the potential for their polymer chemistry to extend the extreme range of conditions that a self-expanding stent has to go through before it is in the human anatomy."

Acknowledging that any products from the joint development effort are "a ways away" from regulatory applications and commercialization, Binch said that a key effort first must be in determining the "mechanical attributes and fatigue attributes, the carrier attributes in all kinds of varying conditions." After that, he said, the company will "probably go to some limited human clinicals [but] whether on our own, or jointly with the big medical device companies, remains to be seen. We're at least a year away before we have definitive proof that [Biomer's coatings] will work on a nitinol substrate."

As to the $400,000 stake Memry is taking in Biomer, Binch described it as "a classic development funding role" commonly pursued by the largest device players. "It's just that we have a hunch that we can move quicker and hopefully be as smart, and maybe a little smarter, than the big guys," he said. The result, he said, will be a "carrier mechanism superior to anybody else's" and available for use not only on peripheral stent systems but also the broad range of implanted medical devices. "For a whole variety of reasons, we can offer flexibility beyond stents."

Biomer has developed a range of high-performance polyurethanes, process technology, components and products for medical device manufacturing. The company's flexible medical grade ZyTar polyurethane-based products already have been approved for use in humans. The company said it also is developing a new generation of biocompatible surface coatings for medical devices and is in late-stage animal trials for an "active" coating for coronary stents as a precursor to human trials.

U.S. unit for CoreValve

CoreValve (Paris), developer of the CoreValve delivery system for percutaneous heart valve replacement based on a catheter and self-expanding stent approach on a beating heart, which avoids open-heart surgery, has established U.S. operations in Irvine, California, and has hired a veteran management and product development team in order to begin operations immediately. CoreValve's sales and marketing activities will be directed from Irvine and will be responsible for managing a network of partner/distributors for the early sales of first-generation ReValving products, which are expected to be available in 2005.

"Establishing U.S. operations and bringing on board exceptional talent – the very best executives working in tissue-valve and catheter development today – is a major milestone for CoreValve," said Dr. Jacques Seguin, the company's founder, chairman and CEO. "It also is important to note that our new U.S. facility is fully equipped for tissue-valve development and catheter work, and has been previously certified by regulatory authorities."

Seguin said that in order to accelerate system development, his company chose to proceed to its initial Phase I feasibility cases with an OEM valve, but now that proof-of-concept has been established for the ReValving procedure, CoreValve has integrated all design and manufacturing steps of the ReValving prosthesis, including the tissue valve component. "We have attracted a team of the world's most experienced and capable valve engineers, giving them the responsibility to design, develop and produce a fully proprietary CoreValve tissue valve," he said.

The management team in the U.S. includes Rob Michiels, president of the U.S. unit and chief marketing officer for the company; Stanley Komatsu, PhD, vice president of valve operations; Than Nguyen, valve development team leader; and Edward Pannek Jr., vice president of catheter operations.

Michiels started his med-tech career with Edwards-Baxter Healthcare, now Edwards Lifesciences (Irvine, California), holding positions of increasing responsibility from 1978-1989. From 1990 to 1991, he was vice president of sales, marketing and business development for Menlo Care, an early-stage vascular access company. From 1992 to 1998, he served as president and chief operating officer of InterVentional Technologies (San Diego), an interventional cardiology start-up that developed the Cutting Balloon device and is now a unit of Boston Scientific (Natick, Massachusetts). In 1998 and 1999, Michiels served as CEO of VenPro, a development-stage venture company in cardiovascular and less-invasive surgery implants. He is a founding partner of Consilium, a medical device market research company that is active in the identification and funding of start-up technologies.

The 8,500-square-foot Irvine operation is a research, development and manufacturing facility – with microbiology, biochemical, tissue-handling fixation and tissue-valve production capabilities. CoreValve said it now is able to focus its development and manufacturing programs – including loading and delivery catheter systems, its ReValving frame, as well as its tissue heart valve and valve-to-frame assembly – within the new specialized facility. The company's sales and marketing activities will be directed from Irvine and will be responsible for managing a network of partner/distributors for the early sales of first-generation ReValving products expected to be available in 2005.

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