CD&Ds

Royal Philips Electronics (Eindhoven, the Netherlands) will lead a European consortium to develop local drug delivery using nanoparticles activated by ultrasound.

Funded with €11 million ($14 million) from the European Union's Framework 7 program to stimulate innovation, the SonoDrugs project will gather 15 industrial partners, university medical centers and academic institutions located across the continent.

The partners will contribute a third of the financing for the four-year program, totaling €5 million ($6.5 million) as well as expertise and in-kind services for research and prototype development.

The program will focus on drug delivery for cancer and cardiovascular disease, exploring the use of existing nanocapsules filled with existing therapeutics as well as the development of new capsule materials combined with new medications, a Philips spokesman, Steve Klink, told Cardiovascular Devices & Drugs.

Although powerful drugs are available to treat cancers and cardiovascular disease they are typically administered systemically as intravenous or oral doses, with very limited control over the distribution of drugs in the body.

The random interaction of these molecules with different tissues and organs is responsible for the heavy side effects often associated with these therapies.

The SonoDrugs project aims to address this challenge by developing drug delivery vehicles that can be tracked by ultrasound or MRI and triggered by ultrasound to release the drugs at a highly targeted site in the desired location. It is hoped that such control of the drug delivery process will increase therapeutic efficiency and minimize side effects, while also providing a means of tailoring the therapy to individual patients.

"New therapeutic options such as externally triggered local drug release at the specific site of disease hold the promise to significantly improve patient care," says Henk van Houten, senior VP of Philips Research and head of Philips' healthcare research program.

He added that targeted drug delivery also holds the potential to tailor therapies for specific patients at different stages of treatment.

One of the program partners, Nanobiotix (Paris), received a European patent covering novel activable particles for use in medical applications in 4Q08.

The core of the company's current nanoXray product is a non-drug agent with at its core an inert and inactive substance called Nbtxr3 coated with a material taken up by cancerous cells, thereby attracting a concentration of particles on the diseased cells while leaving healthy cells untouched.

Introducing a blast of gamma rays from an everyday X-ray unit activates Nbtxr3 locally, setting off tumor necrosis by inducing a chain reaction where a reactive oxygen intermediate blocks the formation of free radicals and arrests the cytotoxic response of tumor cells.

"For Nanobiotix, collaboration with SonoDrugs valorizes the company's know-how in MRI contrast agents and activated therapies as well as nanoparticle design and manufacturing," said President/CEO Laurent Lévy, PhD, who also is co-president of the French Technology Platform on Nanotechnology. He called the SonoDrugs program a "groundbreaking" effort.

Meanwhile Philips said it has two other programs for local drug delivery using ultrasound activation currently in late-stage development.

Philips is working with the University of Virginia (Charlottesville) on a 4-micron microbubble loaded with an anti-cancer therapeutic that is in pre-clinical development and it has announced a collaboration with Celsion (Columbia, Maryland) encapsulating the approved drug Docetaxel s in that company's ThermoDox shell which is activated by MRI-guided high-intensity focused ultrasound system.

Use of proven chemotherapeutics is believed to lower development risk and accelerate speed-to-market for drug-device combination through clinical programs that are less complex.

Yet Klink cautions against this rush to market, saying the development timeline remains fixed closer to a pharmaceutical development than a medical device approval cycle.

"Microbubbles and the drugs they contained are approved for specific indications so that new combinations and new materials means approvals are not as straightforward as a device maker would expect," Klink told CD&D, adding that a 10-year horizon is more likely for any product emerging from the SonoDrugs program.

Other partners on the program include Lipoid (Germany), the university medical centers Erasmus Medical Center (the Netherlands) and Universit ts Klinikum Münster (Germany), and the academic institutions University of Cyprus (Cyprus), University of Gent (Belgium), University of Helsinki (Finland), University of London (UK), University of Tours (France), University Victor Segalen Bordeaux (France), University of Technology Eindhoven (the Netherlands) and the University of Udine (Italy).

3f Aortic Bioprosthesis gets Australian OK

ATS Medical (Plymouth, Minnesota), a provider of cardiac surgery products and services, said the Australian Therapeutic Goods Administration has granted approval for commercialization of the ATS 3f Aortic Bioprosthesis, a tissue valve.

The company describes the 3f Aortic Bioprosthesis as "a revolutionary next-generation stentless pericardial aortic tissue valve that is unlike any other valve."

It said the primary benefit of the device is its tubular design, which restores continuity between the annulus and the sinotubular junction. "By restoring this continuity, the ATS 3f Aortic Bioprosthesis is the only aortic valve that preserves the aortic sinuses and restores native valve stress distribution and physiologic blood flow," ATS said.

It added that this valve design "provides surgeons and patients with a potentially more durable solution to aortic valve replacement."

ATS cited the more than six years of clinical experience with the valve, "confirming excellent safety and efficacy." It said the demonstrated clinical benefit and recent FDA approval of the ATS 3f Aortic Bioprosthesis "are creating excitement and product demand among U.S. surgeons."

ATS Medical is focusing on what it said are "two distinct but operationally synergistic market segments," those being heart valve disease therapy and surgical ablation of cardiac arrhythmias.

Originally founded to develop the ATS Open Pivot Heart Valve, ATS said it is building on the success of that mechanical heart valve in many markets around the world with the ATS 3f brand of tissue heart valves. It said that portfolio addresses conventional open surgery requirements, as well as what it termed "the growing demand for less invasive, sutureless-based procedures."

The company also offers the ATS Simulus annuloplasty product line, as well as ATS CryoMaze products for surgical cryoablation of cardiac arrhythmias.

Taxus Liberté approved in Japan

Boston Scientific (Natick, Massachusetts) said last month it has received approval from the Japanese Ministry of Health, Labor and Welfare (MHLW) to market its Taxus Liberté paclitaxel-eluting coronary stent system in that country. It said the Liberté is the only second-generation drug-eluting stent approved for use in Japan.

The company said it plans to launch the product as soon as reimbursement approval is granted, which is expected in the coming weeks.

Boston Sci said design improvements over the first-generation Taxus Express2 stent include thinner struts to allow better stent deliverability and conformability, as well as a more uniform stent geometry for consistent lesion coverage and drug distribution.

Donald Baim, MD, chief medical and scientific officer of Boston Scientific, said, "The Taxus Liberté Stent is the latest advance in drug-eluting stent technology for Japan," said "Its safety and efficacy have been well demonstrated in multiple clinical studies and years of clinical use."

President/CEO Jim Tobin said, "We are very pleased with this approval, which provides access to proven technology to Japanese physicians and their patients."

The Taxus Liberté stent uses proven paclitaxel-eluting technology, which has been evaluated by what Boston Sci characterized as "the industry's most extensive randomized, controlled clinical trial program," and studied in 35,000 real-world patients enrolled in post-approval registries. More than 4.6 million Taxus stent systems have been implanted globally.

The Taxus Liberté will replace the Taxus Express2 stent, which was launched in Japan in May 2007. It has been approved for sale in the U.S., Europe and other international markets.

Australia's CSIRO develops sensor

The Commonwealth Scientific and Industrial Research Organization (CSIRO; Campbell, Australia) reported in February that it has developed a new concept of measuring surface pressure called the Acoustic Pressure Sensor (APS) and will release an Expression of Interest (EOI) form on Feb. 13 to find a partner who foresees commercial benefit in investing in the further development, production, clinical trials and global market development of the technology.

The sensor is made of an inert material and has no built-in electronics. When the sensor is subjected to sound waves, it reradiates some of the sound waves with the pressure information encoded within the reradiated sound waves. This allows the remote measurement of absolute pressure in the fluid that is in contact with the sensor.

CSIRO said an example of where the APS may be used is in the treatment of aortic aneurysms.

Such aneurysms usually are treated by the use of stent-grafts. If placed correctly, blood will flow through the stent graft and the blood pressure will be removed from the weakened sections of the aorta. If a stent graft is placed incorrectly, then the aneurysm is still exposed to direct blood pressure and it will keep on expanding, eventually rupture and potentially cause a fatal internal injury, CSIRO said.

It said that by placing the sensor on the outside of the stent graft and thereby excluding the aneurysm, the sensor will detect the change in pressure from systemic blood pressure to the lower, internal body pressure.

This device also can be used as a monitoring tool for ongoing patient care.

CURE-AF study is expanded

Medtronic (Minneapolis) reported the expansion of its CURE-AF clinical program with a post-market study in Europe and Canada. Originally being conducted only in the U.S., the study is being carried out in order to secure FDA approval of the company's Cardioblate system for the investigational treatment of atrial fibrillation (AF).

The program will now collect post-market data internationally on the efficacy of irrigated cardiac ablation with radio frequency (RF) energy in AF patients.

The CURE-AF study is investigating the treatment of AF during an open-heart operation such as valve repair or CABG. During the procedure, a surgeon uses Medtronic's Cardioblate System to create a pattern of transmural lesions – lesions that span the full thickness of heart tissue.

The pattern of lesions is modeled after the highly successful Cox Maze procedure. The company said transmurality of the lesions is required for conduction block, which in turn is essential for the prevention of abnormal conduction associated with AF, and for the potential to restore normal heart rhythm.

The Cardioblate surgical ablation system achieves consistent transmural lesions with irrigated RF energy. It is currently indicated for cardiac tissue ablation, and has been used in more than 90,000 procedures worldwide.

Dr. Alexander Wahba, professor of cardiothoracic surgery at St. Olavs University Hospital (Trondheim, Norway), one of the new study participants, said, "We are delighted to be able to join this research effort. If successful in its objectives, CURE-AF will allow the introduction of a new treatment option for many patients who otherwise might endure an untreated arrhythmia and the considerable associated risks."

John Liddicoat MD, general manager of the Structural Heart Disease division in Medtronic's CardioVascular business, said, "AF is ... associated with a five-fold increase in a patient's likelihood of suffering a stroke which can frequently be debilitating and fatal, accounting for one in every 16 American deaths. The more data we have, the better placed we'll be to ensure that this unacceptably high number is reduced."

AGA seeks damages in Germany

AGA Medical (Plymouth, Minnesota) said last month that, following the previously reported favorable patent infringement final ruling by the German court of appeals over Occlutech (Jena, Germany), it has notified Occlutech of the amount of damages that it will seek from Occlutech based on the court's ruling.

No specific amount was reported.

The U.S. company said that after learning that Occlutech has terminated all manufacturing and sales and that its CEO had resigned, it has started proceedings in the insolvency court in Germany to protect AGA's claims for damages.

The lawsuit was brought by AGA in 2006 in Dusseldorf, Germany, seeking to enjoin Occlutech from infringing the German part of AGA's European patent, EP 0 808 138, and for resulting damages.

The final ruling in favor of AGA from the German court of appeals was reported in early January.

AGA develops devices for a range of structural heart repair and circulatory conditions, including treatment of the most common congenital "holes in the heart," such as atrial septal defects and patent foramen ovales.

Peripatch Aegis receives CE mark

Neovasc (Vancouver, British Columbia), a new specialty vascular device company, said it has received CE-mark approval for Peripatch Aegis, its biocompatible product designed to reduce complications from endoscopic surgery. Peripatch Aegis is a buttressing material designed to reinforce the staple line and prevent bleeding and leaks during bariatric and thoracic endoscopic surgical procedures.

The approval enables the company to begin marketing Aegis products for sale in the European Union. The Peripatch Aegis products will be marketed in Europe through Neovasc's network of independent distributors.

"Leakage in endoscopic procedures can result in serious complications for patients, so we specifically designed Peripatch Aegis to enable endoscopic surgeons to reinforce surgical staple lines efficiently and effectively," said CEO Alexei Marko.

Neovasc, formerly Medical Ventures Corp., is a new specialty vascular device company comprised of the former Medical Ventures, Neovasc Medical Ltd. and B-Balloon Ltd.

It develops devices for the vascular and surgical marketplace, with a current line of products including Metricath for intravascular measurement and Peripatch surgical tissue and staple line reinforcement products.

CE mark for Carillon system

Cardiac Dimensions (Kirkland, Washington) reported that it has received the CE mark for its Carillon Mitral Contour System from KEMA Quality BV, a Notified Body located in the Netherlands. The system is a percutaneous treatment for functional mitral regurgitation (FMR).

The company said the CE-mark approval is an important milestone, and that it is now developing plans for commercialization in Europe.

Cardiac Dimensions also recently obtained ISO 13485 (2003) certification, the international standard for quality management systems for medical devices.

The Carillon system combines an implantable device and delivery system. The implant consists of a shaping ribbon between distal and proximal anchors. It is delivered percutaneously via jugular vein access under fluoroscopic guidance. The implant is designed to be positioned, adjusted and gently anchored in the coronary sinus/great cardiac vein to reshape the annulus around the mitral valve, thereby reducing mitral regurgitation.

Pre-clinical and early clinical data have suggested both a reduction in mitral regurgitation and improvements in other key parameters, including NYHA class, 6-minute walk distances and quality of life.

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