The FDA last month approved for marketing two devices that use radiation for the treatment of clogged arteries following balloon angioplasty. With those decisions, two device companies – Cordis (Miami Lakes, Florida), a unit of Johnson & Johnson, and Novoste (Norcross, Georgia) – reached the clearance "finish" line at the same time, although Cordis had received the earlier panel recommendation of approval.
Now, the two firms will begin the race to achieve leadership in this sector, a specialized treatment which attempts to avoid the recollapse of arteries following balloon angioplasty and the placement of stents – a problem that has been the primary drawback to this otherwise beneficial technology.
Novoste's technology is termed the Beta-Cath System. The Beta-Cath is used by reopening the artery and hydraulically placing Strontium-90 beta radiation seeds to the treatment site at the end of the closed-end catheter. The seeds remain there for three to five minutes and are then withdrawn. In trials, the system reduced the rate of restenosis by 36% to 66% as compared to placebo.
The Cordis system is brand-named the Checkmate Gamma Brachytherapy System. It too provides intravascular radiation. As with the Beta-Cath System, a catheter is used to reopen the artery, preliminary to placing a dose of six to 10 seeds of Iridium 192, a low-dose radiation that prevents the formation of clog-forming cells.
While the general technology for the two systems is the same, they have some key differences. While the Beta-Cath system requires only a few minutes to complete, the Checkmate system requires up to an hour for completion.
Additionally, the Beta-Cath system does not require a high degree of shielding, and staff does not have to leave the procedure room during the procedure. With the Checkmate system, the use of gamma radiation requires the doctors to leave the procedure area to avoid exposure.
These factors offer key competitive distinctions between the two, said Larry Haimovitch, president of Haimovitch Medical Technology Consultants (San Francisco, California) who follows the cardiovascular sector for Cardiovascular Device Update and its sister publication Medical Device Week. Because Novoste's procedure doesn't require staff to leave the procedure area, it is less likely "to disrupt the flow of the cath lab," he told CDU. "Cath labs are very finely tuned organisms .... scheduling and a smooth flow, getting more patients in, is really important. And anything that's going to disrupt this flow, like evacuating personnel and putting big shielding in the rooms, is going to be a disruption."
Both systems may be facing some tough brands of oncoming competition in the future, however, with the development of new drug treatments for in-stent restenosis and, ultimately, genetic therapies.
Cordis received a unanimous recommendation of approval for the Checkmate system this past June based on clinical trials that, like Novoste's product, showed a significant reduction in rates of restenosis. The approval was given, however, with conditions. At the time, the company was required to provide more informative labeling, especially for risks to pregnant women and prior radiation patients. The panel also asked the company to provide information concerning the use of a specialized team to carry out the treatment.
Promoting his company's Checkmate System was Jesse Penn, Cordis president. He said the system "offers the unprecedented opportunity to make the winning move in this ongoing battle against in-stent restenosis." He estimated that 100,000 patients in the U.S. currently need treatment for in-stent restenosis, and he specifically noted Checkmate's ability to treat long lesions and lesions in small vessels. "Small vessels and long lesions are especially common among diabetics. The Checkmate system has produced some outstanding efficacy results in a variety of patients, including diabetics," Penn said.
Novoste won approval for the Beta-Cath System in September. One of the lead investigators in Novoste's clinical trials was David Cox, MD, of Presbyterian Hospital (Charlotte, North Carolina). In a statement, Cox said that no previous treatment for in-stent restenosis "have produced results that come even close to the profound results demonstrated with vascular brachytherapy in multiple randomized trials."
Spencer King III, MD, co-director of the Atlanta Cardiovascular Research Institute and the holder of the Fuqua Chair of Interventional Cardiology at Piedmont Hospital (both Atlanta), praised the "small, portable beta radiation system [for providing] a safe, effective and practical method for solving this most difficult problem."
Elsewhere in the product pipeline:
Acusphere (Boston, Massachusetts) has been issued U.S. patents 6,132,199 and 6,045,777 related to the company's intravenous delivery system for gas, which is being developed as an ultrasound contrast agent for the detection of coronary artery disease. One patent covers synthetic polymer compositions used to deliver any fluorinated gas, which the company said is the best class of gases for ultrasound imaging. Acusphere is believed to be the only company with technology for delivering fluorinated gas with synthetic polymers. Acusphere has used synthetic polymers to overcome the limitations of earlier generation ultrasound contrast agents, which are made from natural materials such as albumin, sugars and lipids. The other patent describes technology for how synthetic polymers can be used to engineer important product characteristics. The patent defines the optimum shell thickness for minimizing shadowing and maximizing ultrasound reflection, and covers any gas-filled microparticle for ultrasound contrast imaging with a shell thickness in that optimum range. According to the company, with less shadowing, Acusphere's ultrasound contrast agent, AI-700, can provide clearer ultrasound images with the potential to improve sensitivity and specificity. Acusphere is a privately held drug delivery company that is applying its porous microparticle technology to a number of delivery systems including intravenous delivery of gas and hydrophobic drug delivery.
Boston Medical Technologies (Wakefield, Massachusetts), a maker of office- and hospital-based, noninvasive systems for measuring heart rate variability, has been granted U.S. patent No. 5,984,954, titled "The Method and Apparatus for R-Wave Detection," for its algorithm to measure a patient's heart rate. According to the company, the patented technology eliminates 98% of the work of analyzing a patient's heartbeat, making it more efficient to include heart rate variability testing as a standard of care in a patient's office visit. Heart rate variability can be used as an indicator of autonomic dysfunction as well as neuro degenerative disorders, including Parkinson's disease, multiple system atrophy and peripheral neuropathy. Boston Medical said that with its Anscore Health Management System, patients can have their heart rate variability assessed and documented in response to paced respiration and other controlled exercises. The data are then transmitted through standard phone lines in the physician's office to a process center. The entire test takes only about 15 minutes, according to the company.
Cardima (Fremont, California) has been awarded its 26th patent, the latest for a method of simultaneous detection of electrical signals from multiple locations from within distal branches of the blood vessels of the heart by multiple electrode pairs. "This patent further strengthens our core intellectual property to detect electrical signals in the vessels of the heart," said Gabriel Vegh, president and CEO. "We have a suite of patents that provide coverage for entering and detecting signals within vessels that have applications in diagnosing arrhythmias and congestive heart failure. This technology may also be used in other vasculature of the body," Vegh said.
CardioDynamics (San Diego, California) said it has received a Canadian Medical Device License to market and sell the company's non-invasive heart function monitoring system, the BioZ. The BioZ system is now approved for use in more than 70 countries, the company said.
Use of the Carmeda (San Antonio, Texas) BioActive Surface (CBAS) has been approved by the FDA in a premarket approval application for the Bx Velocity stent from Cordis (Miami Lakes, Florida). This coronary stent currently is marketed in Europe under the Cordis trade name Bx Velocity with Hepacoat. Cordis is a Johnson & Johnson company. CBAS is a heparin coating that retains thromboresistant properties for periods lasting several months. This long-term bioactivity, coupled with the fact that the stable heparin coating does not leave the device surface, differentiates CBAS from other coatings designed to improve the hemocompatibility of blood-contacting devices. The company said that CBAS is the most prevalent and clinically proven thromboresistant coating applied to critical medical devices by U.S. and European device manufacturers. Carmeda AB (Stockholm, Sweden) is majority owned by Norsk Hydro ASA (Oslo, Norway)
Collateral Therapeutics (San Diego, California) said a preclinical study of its myocardial adrenergic signaling technology in the treatment of congestive heart failure was published in Circulation, the journal of the American Heart Association. The study supports the use of an adenylate cyclase gene, AC-6, to boost production of an enzyme in the myocardial adrenergic signaling pathway to improve heart function, the company said.
COR Therapeutics (San Francisco, California) and Schering-Plough (Madison, New Jersey) said a Phase II study of patients with ST-segment elevation myocardial infarction showed Integrilin, an antiplatelet agent, combined with half-dose alteplase significantly improved blood flow through blocked arteries compared to full-dose alteplase alone. Both compounds are approved by the FDA. The 300-patient trial indicated that the therapy restored normal blood flow through clogged arteries within an hour in 56% of patients compared with 40% in patients treated with full-dose alteplase alone.
Critikon (Tampa, Florida) received FDA market clearance for the Dinamap Pro 1000 featuring electrocardiogram (ECG) capabilities. Designed specifically for the subacute care market, the system combines ECG with three other technologies. In addition to 3-lead ECG capabilities, the monitor uses Nellcor pulse oximetry by Mallinckrodt (St. Louis, Missouri), IVAC predictive thermometry by Alaris Medical Systems (San Diego, California) and Dinamap ASAP by Critikon. The company said that this NIBP technology automatically adjusts for lower inflation pressures on blood pressure readings. Critikon makes noninvasive patient monitoring systems
Epix Medical (Cambridge, Massachusetts) said its contrast agent MS-325 can be used to produce detailed images of arterial plaque and vessel wall inflammation using a signal magnetic resonance exam. Preliminary results of an eight-patient trial of the agent in that usage indicate, Epix said, a dramatic improvement in imaging arterial walls and adjacent plaque with MS-325 compared to standard magnetic resonance angiography.
Guidant (Indianapolis, Indiana) has enrolled the first patients in a clinical trial to determine the safety and feasibility of stenting in patients with cerebrovascular disease. Guidant's SSYLVIA (Stenting in SYmptomatic atherosclerotic Lesions of Vertebral and Intracranial Arteries) trial is a non-randomized, prospective study that will enroll approximately 30 patients with cerebral atherosclerosis – the narrowing or hardening of arteries that occurs over time. This study will be conducted at five centers in the U.S., as well as in eight centers elsewhere. The SSYLVIA trial will use Guidant's Neurolink System, which is designed to treat atherosclerosis of the intracranial arteries and extracranial vertebral arteries – cerebral vessels that travel up the back of the neck on either side of the spinal cord and join at the base of the skull. Guidant's investigational system is comprised of a balloon dilatation catheter for pre- and post-dilatation and the Neurolink stent, which is pre-mounted on a delivery catheter. Guidant provides products and services for the treatment of cardiovascular and vascular disease.
Hypertension Diagnostics (St. Paul, Minnesota) has received FDA clearance to market the CVProfilor DO-2020 CardioVascular Profiling System for use by physicians and other health care providers to noninvasively screen patients for the presence of cardiovascular disease. In addition to measuring blood pressure values (systolic, diastolic and mean arterial pressure) and heart rate, the system calculates pulse pressure, body surface area and body mass index, and provides indications of arterial elasticity. The company says that this system determines both large- and small-artery elasticity indices that can be used as an initial clinical screening device to determine if patients have potential underlying vascular disease that might require more specific diagnostic evaluations.
Intuitive Surgical (Mountain View, California), a maker of robot-assisted surgical systems, said the cardiac team at University Health Systems of Eastern Carolina/Brody School of Medicine at East Carolina University (Greenville, North Carolina) successfully completed North America's first robotic mitral valve cardiac surgery trial using the company's da Vinci Surgical System. W. Randolph Chitwood Jr., MD, led the cardiac team that successfully completed the series of 10 cases. The trial, conducted to determine the feasibility of using robotics to assist in cardiac mitral valve surgery, was completed in early November. The patients ranged in age from 18 to 80 and underwent mitral valve repair procedures using Intuitive's robotic technology. The FDA has authorized an additional 10-patient extension of the university's trial, which began on Nov. 7.
Medtronic (Minneapolis, Minnesota) has launched its Sprint Quattro Model 6944 quadripolatr defibrillation lead in Europe, the Middle East and Africa. The new lead, which is designed for transvenous use with implantable defibrillators, incorporates four electrodes along its length. Two are dedicated to pacing and sensing cardiac electrical signals, while two coil electrodes deliver energy to the atrial inner surface. Medtronic said the lead diameter is the world's smallest for this type of product, making handling and implantation easier.
Meridian Medical Technologies (Columbia, Maryland) has received marketing clearance from the FDA to market the CardioBeeper CB12/12 cardiac monitor, a new device that allows heart patients to transmit a complete 12-lead electrocardiogram (ECG) from home or office over a standard telephone line. The CB12/12 is expected to replace the CB12L currently marketed through Meridian's marketing partner to Israel and portions of Europe. Recently introduced in Israel, the system is manufactured by Meridian and marketed by Shahal Medical Services (Tel Aviv, Israel). With this new FDA approval, Shahal said it intends to market the device in the U.S. Primarily designed for monitoring patients who have cardiac-related symptoms such as chest pain or irregular heartbeats, the monitor transmits data that is interpreted by medical personnel who can provide diagnosis, advice and treatment when appropriate. Meridian Medical has holdings in noninvasive cardiopulmonary diagnostics, and makes auto-injector drug delivery systems.
Micro Therapeutics (MTI; Irvine, California) received CE-mark approval for its Onyx Liquid Embolic System for the treatment of brain aneurysms. Onyx, a liquid embolic material, is delivered through MTI's micro catheters directly into an aneurysm. Once inside, Onyx transforms into a spongy polymer mass intended to seal off the aneurysm, thus reducing the risk of rupture and subsequent stroke. In July, MTI initiated its CAMEO (Cerebral Aneurysm Multi-Center European Onyx) Study. By year-end, MTI expects to have eight European sites involved in this study, which will serve to provide data as part of the company's commercialization plan. MTI received FDA approval in August. Commercial orders for Europe are expected to commence in early 2001 and will be handled by Guidant, MTI's exclusive distribution partner in Europe. Micro Therapeutics makes minimally invasive devices for the diagnosis and treatment of vascular disease.
NeuroVasx (Plymouth, Minnesota) has gained CE-marking for its Sub-Microinfusion cerebrovascular catheter, which is used to deliver diagnostic imaging agents, like contrast media, into the neurovasculature for the diagnosis of acute thrombotic occlusions of the brain.
Pulse Metric (San Diego, California) will add the brachial arterial vascular compliance (BAVC) analysis function to its DynaPulse blood pressure monitors, for use by physicians and medical professionals. Arterial vascular compliance is a measurement of the artery's ability to expand and contract during pulsatile blood flow. DynaPulse records the pulsation signal for determining arterial compliance through a noninvasive cuff at the same time it measures blood pressure at the brachial artery, on the upper arm. The company says that growing scientific evidence suggests that measurement of arterial compliance, or vessel elasticity, may provide an earlier and more specific predictor of cardiovascular disease risk than blood pressure alone. Pulse Metric develops technologies for the prevention, detection and management of hypertension, heart failure and associated cardiovascular diseases.
St. Jude Medical (St. Paul, Minnesota) released a new electrophysiology catheter to assist clinicians in the diagnosis and treatment of supraventricular tachycardias. The Livewire Duo-Decapolar catheter, with special electrode spacing, allows physicians to simultaneously map in both the right atrium and coronary sinus with a single steerable catheter. The company said this new model in the Livewire product line can reduce the number of catheters used during an electrophysiology procedure as well as the number of vascular access sites in the patient. The Livewire product line from St. Jude includes mapping and ablation catheters for the treatment of various arrhythmias. St. Jude Medical makes medical device products for the cardiac rhythm management, cardiology and vascular access, and heart valve disease management markets.
Thoratec Laboratories (Pleasanton, California) has received approval from the FDA of an IDE supplement allowing for an additional 20 patients to be enrolled in an existing clinical trial using the company's TLC-II Portable VAD (Ventricular Assist Device) Driver. The company recently announced the submission of a premarket approval supplement seeking FDA approval in the U.S. for use of the device for excursions away from the hospital and for discharge to an off-site medically monitored residence. The TLC-II is a small, lightweight device used to power Thoratec's VAD, which pumps blood to the body in heart failure patients awaiting transplant or recovery from open-heart surgery. The device has been approved for sale in Europe for more than two years. Thoratec has filed an investigational device exemption application for a new clinical trial involving home discharge of patients being supported by the TLC-II Driver while awaiting a transplant or recovery of the natural heart. Thoratec Laboratories makes medical devices for circulatory support and vascular graft applications, all of which incorporate its proprietary biomaterial,Thoralon.