A CDU

In conjunction with the Japan Heart Rhythm Society annual meeting in Tokyo in early July, Medtronic (Minneapolis) reported Ministry of Health, Labor and Welfare (MHLW) approval of the Medtronic InSync III Marquis cardiac resynchronization therapy-defibrillator (CRT-D) in Japan. In addition, MHLW has granted reimbursement approvals for CRT-D devices as a result of Medtronic’s work with the Japanese regulatory body.

The InSync III Marquis system combines cardiac resynchronization and defibrillation therapies in a single device for the treatment of moderate-to-severe heart failure in patients who are at risk for sudden cardiac arrest. The device was expected be available for sale in Japan at the beginning of this month.

Marshall Stanton, MD, vice president and general manager of the Cardiac Rhythm Disease Management business for Medtronic in Japan, said the MHLW approval of the CRT-D device continues the company’s 30-year tradition of leadership in bringing new medical technologies to market in that country. “Beginning with the introduction and reimbursement of ICDs in Japan in 1996 to cardiac resynchronization therapy-pacemakers in 2004, and now CRT-D, we continue to innovate to bring forward novel therapies and technologies for managing heart failure and heart rhythm disorders, benefiting physicians and their patients,” Stanton said.

About the size of a small stopwatch, the InSync III Marquis device offers sequential bi-ventricular pacing for more precise pacing of the two lower chambers of the heart - and a comprehensive heart failure management report to assist physicians in overall management of heart failure symptoms.

The system includes the advanced therapies of the Marquis DR implantable cardioverter defibrillator, which the company said is the most popular ICD in Japan. The ICD rapidly detects and terminates fast ventricular heart rates that could lead to sudden cardiac arrest, which takes the lives of about 80,000 people in Japan annually. The InSync III Marquis system also includes Medtronic’s Patient Alert feature, which notifies patients with a series of tones when follow-up care is needed.

Cardiac resynchronization therapy is designed to coordinate the contraction of the heart’s two lower chambers and improve the heart’s efficiency to increase blood flow to the body. More than 1.5 million Japanese suffer from heart failure, which Medtronic said is the only major cardiac condition that continues to grow in prevalence.

The FDA approved the original InSync system in August 2001. The InSync III Marquis CRT-D device has previously been approved for use in numerous countries around the world, including the U.S. and Europe.

Separately, Medtronic said it has received regulatory approval from the government of China to begin selling its Endeavor drug-eluting coronary stent (DES) system in that country. Made of a cobalt alloy and built on the same platform as the popular Medtronic Driver bare-metal stent, the Endeavor DES has a modular architecture designed to enhance deliverability. In addition to the drug compound zotarolimus (ABT-578), Endeavor is coated with phosphorylcholine, a polymer designed to simulate the outside surface of a red blood cell and mimic the structure of the natural cell membrane, which aids in the healing response.

The company said China is one of the fastest-growing vascular markets in the world and one of the largest DES markets in Asia at more than $100 million. About 70,000 drug-eluting stents are implanted each year in China.

Dr. Ge, of Zhong Shan Hospital and co-chairman of the Shanghai Institute of Cardiovascular Diseases, said, “Evidence from the Endeavor clinical trials and from commercial use around the world has confirmed excellent outcomes for patients. The number of times patients are required to return for repeat procedures is low and there also is a low rate of clinically adverse complications.”

In May, Medtronic presented data at the EuroPCR (Paris Course on Revascularization) conference that provided clinical evidence demonstrating the long-term safety and efficacy of the Endeavor stent. In addition to low rates of repeat procedures, the three-year and two-year results from the ENDEAVOR I and ENDEAVOR II clinical trials demonstrated low rates of major adverse events such as death and myocardial infarction.

There also was no late stent thrombosis reported in either of the two trials. Endeavor patients who participated in the trials for at least one year, there have been no reported cases of late stent thrombosis, the formation of dangerous blood clots that potentially can lead to heart attacks or death.

“The Endeavor stent is proven to be safe and effective, and it is among the most deliverable DES products on the market,” said Max Muhs, vice president of Medtronic’s vascular business in China. “We believe it offers the best combination of features among the drug-eluting stents available in Asia.” He added that the approval for commercialization of the stent “further strengthens our commitment in China, following the recent opening of our physician training center in Beijing.”

With regulatory approval now granted in China and the earlier announcement of reimbursement in France, the Endeavor drug-eluting coronary stent is commercially available in some 100 countries worldwide. The stent received CE-mark approval in Europe in July 2005. Medtronic anticipates approval in the U.S. in 2007.

Cordis’ 3rd-generation DES is 1st to get CE mark

The Cypher Select Plus from Cordis (Miami Lakes, Florida) has become the first third-generation drug-eluting stent (DES) to receive CE mark approval. The company said it would begin launching the product in Europe in September, with full market launch by year-end. Cordis said the enhanced stent delivery system of the new DES “offers exceptional deliverability, as well as the excellent, long-term clinical performance for which the Cypher stent is known.”

“A broad range of clinical studies has demonstrated that the Cypher stent is an effective and safe treatment for coronary artery disease,” said Philip Urban, MD, director of invasive cardiology at La Tour Hospital (Geneva, Switzerland) and the coordinating investigator of e-SELECT Registry, a global registry designed to assess the performance of the Cypher Select family of stents in daily clinical practice. He said the Cypher Select Plus “builds on that tradition by featuring enhancements that ease the delivery of the stent to the site of a lesion.”

In addition to a flexible stent design and short tip, Cordis said the new DES features the Cyph2onic hydrophilic coating technology, which it said is “significantly more lubricious than previous Cypher stent products, greatly increasing a physician’s ability to successfully navigate challenging coronary arteries.”

Dennis Donohoe, MD, vice president of worldwide clinical and regulatory affairs for Cordis, said physicians “will experience unprecedented ease in the delivery” of the new stent. The company said it is “aggressively building” its manufacturing capacity for the Cypher Select Plus launch. It said it is “committed to ensure that physicians have ready access to the product as it becomes available in various countries outside the U.S.”

Cordis introduced the first second-generation drug-eluting stent, the Cypher Select, outside the U.S. in 2004. The Cypher stent is available in more than 80 countries.

Cordis tops 50 enrollees in 2nd-generation trial

CoreValve (Irvine, California/Paris) said it has completed minimal enrollment in a clinical trial involving its second-generation CoreValve Percutaneous ReValving System. Fifty-one patients at seven investigative sites in Europe and North America have now successfully undergone percutaneous aortic valve replacement (PAVR) with the second-generation, 21 Fr ReValving system to treat either aortic stenosis, aortic regurgitation or failed-tissue-valve-prosthesis conditions. Each of the patients was at high risk for open-heart surgery.

CoreValve said it expects to use the results of this trial as part of a future CE-mark submission seeking approval to market the ReValving system in the European Union. “We have developed a breakthrough system for replacing an aortic valve via a peripheral, intravascular, percutaneous approach on a beating heart,” said Jacques Seguin, MD, PhD, chairman, CEO and founder of CoreValve.

“The result is that 100% of the patients discharged from various hospitals involved in our second-generation clinical trial continue to show improved cardiac function with no complications, while enjoying a dramatically enhanced quality-of-life at follow-up now out to 17 months in some cases,” he said. “We are confident that the results of this study, when completed, will be part of the strong foundation for a CE-mark submission.”

Rob Michiels, president and COO, said the trial has “dramatically underscored the significant benefits of our second-generation ... system compared to the first-generation, system. The smaller catheter greatly improves the ease of the ReValving procedure, and our investigators are now routinely accessing, delivering and placing our porcine pericardial-tissue bioprosthesis in less than 15 minutes.”

He said the company is “moving immediately toward another clinical trial using our third-generation system, whose delivery catheter has been downsized to 18 Fr. This further reduction in size is particularly important to the interventional cardiologist when accessing a diseased aortic valve via calcified and tortuous vessels.” Michiels said CoreValve “fully expects” the 18 Fr system to also make alternative access through the subclavian arteries feasible.

Study cites causes of thrombosis

The results of a new study providing insight into the causes of thrombosis were presented last month at the 11th annual congress of the European Hematology Association (EHA) in Amsterdam, the Netherlands

The study was conducted by the University Medical Center Utrecht, (UMCU) in the Netherlands, in conjunction with the University of Cambridge in the UK. It successfully identified the precise location where the von Willebrand-factor protein adheres to collagen – the first step in thrombus formation. The researchers said this discovery makes it possible to begin developing medication to block platelet adhesion, marking a major step forward in the treatment of arterial thrombosis, or atherosclerosis.

Atherosclerosis begins with the inside vessel wall becoming “rough,” causing platelets to become stuck, which can, in turn, lead to the formation of blood clots. If thrombosis completely blocks the blood vessel, the downstream tissue no longer receives oxygen, causing an infarction to occur in the heart or in the brain.

The platelets stick to the damaged vessel walls via an “adhesive protein,” the von Willebrand-factor protein, named after its discoverer, Erik von Willebrand. The protein forms a bridge between the platelets and the collagen component of the vessel wall, which is exposed in damaged vessels. Professor P.G. de Groot, researcher at UMCU, said, “‘Further study may allow us to reduce adhesion of blood platelets to arteriosclerotic blood vessel walls. This could open doors to new treatments allowing us to influence the clinical consequence of arteriosclerosis.”

Also at the EHA meeting, two pioneering studies in the field of stem cell transplantation were presented. The first, conducted at the Leiden University Medical Center, demonstrated for the first time that environment-specific cells can play a role in positively influencing rejection reactions following stem cell transplants.

The second study, from the San Raffaele Scientific Institute (Milan, Italy), showed that a “suicide” gene can be used to cut short rejection reactions following stem cell transplants.

Gilde reports 1st closing of fund at $107M

Gilde Healthcare Partners (Utrecht, the Netherlands), a life sciences venture capital group, has reported the first closing of Gilde Healthcare II (GHC II), its second life science venture fund. Current commitments to GHC II amount to EUR 85 million ($107 million), with further closes anticipated later this year. The fund expects to reach a final close of at least EUR 125 million ($158 million), the company said.

GHC II has attracted a number of major new investors as well as “significant support” from existing investors, Gilde said. It said the fund has been raised in a relatively short time frame from investors across continental Europe and that further closes may include investment from the U.S. Investment in the first close included 47% from banks, 24% from fund of funds, 11% from pension funds, 6% from biotech cross-over funds and 12% from family offices and management.

GHC II will invest principally in privately held European start-up companies, Gilde Healthcare said. It will invest broadly across the healthcare sector including therapeutics, diagnostics, medical devices and enabling technologies. Investment size will range between EUR 1 and EUR 12 million per portfolio company.

Pieter van der Meer, one of the managing directors, said, “This is a very satisfying result in what is generally regarded as a challenging fund-raising environment. We are delighted to have attracted such significant support from both new and existing investors and expect to announce further commitments to GHC II soon. We believe that the timing for investing in healthcare is right.”

PreMed tops trial enrollment target

Predictive medicine company PreMD (Toronto) said that it has exceeded its enrollment target in the 600-subject PASA (Predictor of Advanced Subclinical Atherosclerosis) study with 650 patients. PASA is examining the relationship between skin tissue cholesterol (sterol) and carotid intima media thickness (CIMT), which refers to the thickness of the first two inner layers of the carotid artery wall. CIMT is an established predictor of heart attack and stroke.

The PASA study is aimed at supporting broader regulatory clearance for the PREVU(x) Point of Care Skin Sterol Test as well as PREVU(x) LT Skin Sterol Test as a tool to identify asymptomatic patients at risk of a primary event, such as heart attack or stroke.

Dr. Brent Norton, president and CEO, said, “We will be analyzing the data in the coming months and expect to be in a position to make various regulatory submissions to the FDA and in Canada and Europe before the end of the year.”

PREVU(x) non-invasively measures the amount of cholesterol that has accumulated in the skin tissues, as opposed to blood. No fasting or other patient preparation is required for the test. Clinical studies have shown that as cholesterol accumulates on artery walls it also accumulates in other tissues, including the skin. High levels in the skin are correlated with higher incidence of coronary artery disease.

PREVU(x) POC is cleared for sale in Canada, the U.S. and Europe.

The company’s research and product development facility is at McMaster University (Hamilton, Ontario).

U.S. trials OK’d for Topspin IVMRI

TopSpin Medical (Lod, Israel) has received FDA approval to start clinical trials in the U.S. of its advanced-generation IntraVascular MRI (IVMRI) catheter, intended for the detection and characterization of lesions in the coronary arteries. Clinical trials with the IVMRI catheter already have been conducted in more than 70 patients in Europe and Israel.

TopSpin said that it expects to receive the CE Mark for marketing the product in Europe by the end of this year, and FDA marketing approval in the U.S. by the middle of 2007. The company’s IVMRI catheter technology enables MRI to be performed in the clinic for the first time with no external magnets.

The company said it has completed the development of a prototype of its advanced-generation IVMRI catheter, in accordance with the planned schedule. This is “a further technological breakthrough in the miniaturization of the sensors and in the ability to integrate a number of sensors for imaging longer arterial segments in a short acquisition time,” TopSpin said.