Saying that it was looking for a "windfall," CryoLife (Kennesaw, Georgia) filed a premarket approval application (PMA) for its porcine CryoLife-O-Brien Stentless Heart Valve. The company said that if approved, the product would generate revenue that the company never expected to receive from a patent that was acquired for a different technology.
CryoLife, a developer of cryopreserved and tissue-engineered implantable heart valves, vascular and orthopedic reconstruction grafts, and surgical adhesives, said that the O'Brien heart valve will be directed towards the adult aortic valve replacement market, which it estimated at over $250 million in the U.S. It said that this complements the estimated $60 million per year pulmonary heart valve replacement market, in which CryoLife already competes.
The company said that the PMA is based upon the results of several hundred human implants performed in the European Union and Australia. The O'Brien stentless heart valve has been implanted in Europe since 1991, and the device has been distributed in Europe since 1996, when it was awarded the CE mark. The valve was designed by Mark O'Brien, MD, a senior cardiac surgeon at Prince Charles Hospital (Brisbane, Australia) in the late 1960s. The proposed medical indication for use of the O'Brien valve in the U.S. is in surgeries for patients diagnosed with narrowing of the aortic valve (aortic stenosis). The valve is targeted for patients over the age of 55 who wish to avoid the long-term anticoagulant drug therapy that is required with a mechanical valve implant.
"We acquired the O'Brien valve technology back in the mid-1990s," said Roy Vogeltanz, vice president, corporate communications. "It was already approved in Europe, but we hadn't planned on trying to gain approval for it in the U.S. because of the cost of the U.S. clinical trials," he told Cardiovascular Device Update's sister publication, Medical Device Daily. What changed the company's mind, he said, was the approval of the Hancock II by Medtronic (Minneapolis, Minnesota) without doing U.S. clinical trials "That caught our eye," Vogeltanz said.
He said one advantage to the porcine valve over mechanical valves is the fact that a patient doesn't have to take blood thinners "That in essence turns patients into hemophiliacs." He acknowledged that the pig valves have to be replaced, on average, every 10 years or so. "It's a tradeoff if you don't want to take all the anticoagulation medications, so it's a quality-of-life issue."
Vogeltanz called the product "a very unique composite valve," noting that "we're taking three non-coronary leaflets and sewing them together to make one valve." He added that O'Brien thought very clearly about making a valve that could expand like our own valves do. The valve "doesn't have a sewing ring; it doesn't have any synthetic materials that would keep it from expanding. These valves will actually expand with the heart as it opens and closes." He also said that since the valves expand at a much better rate, this will reduce the stress on the leaflets, making the valve, theoretically, last longer.
CryoLife actually acquired the O'Brien technology for the development of what it thinks will be one of its flagship products, the Synergraft valve. The Synergraft is a tissue-engineered valve that already has European approval. "That product," Vogeltanz said, "has the potential to put all the other heart valves out of business, because if you can supply a valve that would remodel itself as our own heart valves do, why would you need anything else?" He also said that this technology could apply to vascular grafts and orthopedic tissues. The O'Brien approval is "just icing on the cake for the company," he said.
Elsewhere in the product pipeline:
Arrow International (Reading, Pennsylvania) said that two additional patients have received implants of the LionHeart, the company's implantable Left Ventricular Assist System (LVAS), since its last update in mid-June. A total of 21 patients, 14 in Europe and seven in the U.S. have now received the device. Loyola University Chicago Medical Center (Chicago, Illinois) implanted the seventh U.S. patient and the German Heart Center (Berlin, Germany) implanted the 14th European patient with the LionHeart device during the month of July. All seven U.S. patients have now been enrolled in the Phase I U.S. feasibility trial authorized in February under an FDA investigational device exemption. The company also reported that the first U.S. patient to receive the device at Penn State Milton S. Hershey Medical Center (Hershey, Pennsylvania) died on July 24, with the death attributed to complications from GI (gastrointestinal) bleeding that the patient developed several weeks after surgery. In response to the company's request to enroll seven more U.S. Phase I patients, the FDA has requested additional details relating to the device and the progress of U.S. and European patients who have received the device to date. Considering the time required to provide this information and for the FDA to review it, Arrow said the earliest opportunity for including additional U.S. patients in the Phase I trial is late this month. The company said it still believes that a pivotal Phase II U.S. trial can begin later this year.
Avant Immunotherapeutics (Needham, Massachusetts) began a placebo-controlled Phase II study of its cholesterol management vaccine (CETi-1) in about 200 patients with low levels of high-density lipoprotein cholesterol. The study will evaluate the safety, immunogenicity and dose-response relationship of the product in patients who receive an initial immunization followed by boosters. The principal endpoint is the change in HDL cholesterol measured after the six-month booster. CETi-1 is designed to raise serum HDL cholesterol levels by blocking the transfer of cholesterol from HDL to low-density lipoprotein.
Biocompatibles International (Surrey, UK), and British Biotech (Oxford, UK) began trials of the Batimastat BiodivYsio stent, a drug-coated device designed to reduce restenosis in patients who have undergone coronary angioplasty. The multicenter trial is evaluating 150 patients for safety and efficacy, which will be measured by angiographic restenosis at six months following deployment of the device.
Boston Medical Technologies (Wakefield, Massachusetts), a developer of office- and hospital-based systems for noninvasive measurement of heart rate variability (HRV), reported completing 10,000 patient tests with its Anscore Health Management System. The company said it has compiled the largest diabetic patient database of HRV tests in the world, making it the leader in testing and data analysis of the autonomic nervous system. According to this critical data of patients tested with the Anscore System, 46% of people with Type 1 diabetes and 56% of people with Type 2 diabetes were found to have abnormal HRV results. By testing patients' HRV using the Anscore System and determining the status of their autonomic nervous system health, physicians can use the test as an early warning signal for diabetic autonomic neuropathy and immediately begin providing patients with specific recommendations for prevention and treatment. The company said the Anscore Health Management System enables treating physicians to measure a patient's heart rate variability during a routine office visit. Published clinical data reports that heart rate variability testing can be used as an indicator of autonomic nervous system dysfunction – an initially asymptomatic condition prevalent in people with diabetes. The company 510(k) approval allows the Anscore System to report normal ranges for heart rate variability based on device-specific reference values. The data is then transmitted through standard phone lines in the physician's office to Boston Medical's process center, where analysts apply the patented algorithm to calculate standard indices and ratios for heart rate variability.
Boston Scientific (Natick, Massachusetts) reported receiving Japanese reimbursement approval for its Radius coronary self-expanding stent. The stent is available in 14 mm, 20 mm and 31 mm lengths and is designed for clinical applications requiring conformability and a soft delivery touch, such as tapered vessels, lesions on a bend and saphenous vein grafts (SVGs), according to the company. The company received Japanese regulatory approval to market the device based on a multicenter trial involving more than 100 patients. The study found a low restenosis rate of 17% in all lesions. The Radius stent was first launched in the U.S. on an over-the-wire platform in 1998 and on a Monorail platform in both the European and Intercontinental markets last year. It is available on both platforms in Japan. The Radius stent system features a sheath delivery system and a nickel-titanium alloy with temperature-set shape memory. This allows the stent to navigate tortuous arteries and gently expand within an artery. The result is an atraumatic stent placement, according to the company.
CV Therapeutics (Palo Alto, California), began Phase II trials of CVT-3146, a selective, short-acting A2A adenosine receptor agonist that is being developed to selectively increase coronary artery flow for the potential use as an adjunctive pharmacological agent in cardiac perfusion imaging studies. The purpose of the trials is to determine the tolerability of CVT-3146 and its effect on coronary blood flow in patients undergoing a clinically indicated cardiac catheterization.
DuPont Pharmaceuticals, a wholly owned subsidiary of DuPont (Wilmington, Delaware), said the FDA approved its ultrasound contrast agent Definity (vial for perflutren lipid microsphere injectable suspension). Definity increases the power of echocardiography (ultrasound of the heart) by enabling doctors to obtain clearer images of the heart than is often possible with echocardiography alone, according to DuPont. As a result, Definity may provide earlier and more definitive diagnoses for millions of difficult-to-image patients at risk for heart disease. Definity is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. By improving the visualization of the primary pumping chamber of the heart, ultrasound with Definity may better distinguish between normal and abnormal heart structure and motion – two critical indicators of cardiac health. Definity is the only ultrasound contrast agent in the U.S. that is nonblood-derived, eliminating the risks and concerns associated with the use of blood-based products, DuPont said. The company plans to introduce Definity early this fall.
Hemosol (Toronto, Ontario) said it has been asked by the FDA to make further changes to the trial protocol for its Hemolink hemoglobin-based oxygen carrier to ensure acceptability of the efficacy analysis for inclusion in a biologic license application. The company said that due to this new development, it no longer believes a completion date in 1Q02 is achievable for the pivotal study.
Idun Pharmaceuticals (San Diego, California) presented data showing caspase inhibitors significantly decreased heart muscle damage following induction of a heart attack in a rat model of disease. It showed a 55% reduction in heart tissue damage even when administered one hour after the attack.
Imatron (South San Francisco, California) reported the publication of 16 papers and editorials in the July 19 supplement to the American Journal of Cardiology covering early coronary atherosclerosis detection using computed tomography technology – primarily electron beam tomography (EBT) – for the detection of coronary artery calcification as a surrogate marker of asymptomatic atherosclerosis. New data included percentile tables compiled from more than 58,000 EBT studies demonstrating the distribution of various degrees of coronary artery calcification among asymptomatic individuals.
Innercool Therapies (San Diego, California) reported initiating a clinical study to investigate the use of its Celsius Control System in patients who develop a fever after suffering a ruptured brain aneurysm (hemorrhagic stroke). The system is an endovascular catheter technology that exchanges heat directly with blood flowing in the vessels of the body to induce and/or reverse hypothermia, which has the potential to prevent tissue or organ damage during periods of ischemia during stroke and heart attack, or for temperature control in surgical and critical care applications. The study will be conducted at Massachusetts General Hospital (Boston, Massachusetts). Innercool's Celsius Control System combines an endovascular catheter and circulating set with a console drive unit, which controls the temperature of a circulating saline solution. The catheter is placed into the inferior vena cava via the femoral vein. Blood is cooled or warmed as it flows past a proprietary, alloy-based element at the distal end of the catheter, allowing for controlled cooling and/or re-warming of the patient. The system does not require fluids to be perfused into the body, nor does it require blood to be circulated outside the body. The company also announced the expansion of its ongoing T.C.A.S. (Temperature Control during Aneurysm Surgery) clinical trial of the system, with the addition of 10 clinical investigation sites in the U.S. The trial is designed to induce hypothermia, maintain a target temperature and subsequently restore normothermia during surgical repair of unruptured brain aneurysms.
Instromedix (San Diego, California), a subsidiary of Card Guard Technologies, reported the launch of the King of Hearts Express+, a 30-day cardiac event monitor that includes new auto-trigger technology with a standard two-electrode lead set. The Express+ stores patient-activated events and automatically records certain types of arrhythmias, such as unusually fast or slow heart rates. Instromedix specializes in noninvasive, portable cardiac event monitoring and pacemaker follow-up systems.
Novoste (Norcross, Georgia) said it has completed European Union requirements for approval to affix the CE mark to its next-generation, smaller-diameter catheter system, the Beta-Cath 3.5F System, to reduce the incidence of restenosis following percutaneous coronary interventional procedures. The Beta-Cath 3.5F System, offered in Europe with both a 40 mm and 60 mm radiation source train, includes the smallest-diameter vascular brachytherapy catheter commercially available. The Beta-Cath 3.5F System is designed to be used with a 6 Fr guiding catheter, which Novoste said is the most common guide catheter size used in Europe. The company said the smaller catheter diameter and multiple radiation lengths should allow the Beta-Cath 3.5F System to be particularly useful in the treatment of smaller coronary arteries, thus expanding the market opportunity for vascular brachytherapy. Novoste also said that it has submitted an application to the FDA for a premarket approval supplement for the Beta-Cath 3.5F System, to be used for the treatment of in-stent restenosis.
Radiance Medical Systems (Irvine, California) received a conditional investigational device exemption from the FDA to begin U.S. enrollment in its peripheral vascular study, RAPID (Radiation After PTA Is Done). Enrollment is scheduled to begin late in 3Q01 following investigational review board approval at the participating sites. Initial enrollment in the RAPID Study began in Europe in May. The study is an international clinical study designed to enroll up to 50 patients to evaluate the use of the RDX Radiation Delivery System in preventing the recurrence of atherosclerotic blockage following interventional treatment in the superficial femoral artery and popliteal arteries, the primary arteries of the mid- and lower leg. The study will include both de novo and in-stent lesions. The RDX Radiation Delivery System is commercially available in the European Union and select other countries outside the U.S.
Vasomedical (Westbury, New York) reported that the International EECP Patient Registry (IEPR), coordinated by the department of epidemiology in the University of Pittsburgh Graduate School of Public Health (Pittsburgh, Pennsylvania) reached its enrollment goal of 5,000 patients. Data collected by the IEPR represents the single largest current pool of information available anywhere in the world on patient outcomes associated with enhanced external counterpulsation (EECP) therapy, according to Vasomedical. Established in 1998, IEPR documents the safety and efficacy of EECP therapy during and immediately after the treatment period. EECP therapy serves to increase circulation in areas of the heart with less than adequate blood supply and may restore systemic vascular function and is currently indicated for use in patients with stable or unstable angina, acute myocardial infarction and cardiogenic shock. According to IEPR data, almost 80% of patients experience a reduction in angina following treatment with EECP therapy, a benefit shown to persist for up to two years after treatment. The status on the 5,000 patients currently enrolled in the IEPR will be tracked for at least three more years, providing follow-up data on the therapy's long-term benefit. The IEPR enrolls consecutive patients starting EECP therapy for the treatment of angina pectoris from participating EECP treatment centers.