The latest-generation small vessel stent from Medtronic (Minneapolis, Minnesota), the S660 With Discrete Technology Coronary Stent System, has received FDA marketing clearance. The newest member of the Medtronic AVE (Santa Rosa, California) family of stents, the S660 was developed for vessels that are 2.2 mm to 2.9 mm in diameter, and its design provides for navigation through tortuous anatomy and accurate placement. Available in both over-the-wire and rapid exchange versions, the S660 is the lowest profile stent available on the market, according to Medtronic. Usable by a single operator, the stent allows for perfusion of blood through the guidewire lumen during deployment and features new six-crown architecture for more scaffolding support in holding the vessel open, critical for treating smaller vessels. The S660 can be delivered like a balloon and is indicated for abrupt or threatened closure of vessels after coronary arteries have been opened with balloon catheters in percutaneous transluminal coronary angioplasty (PTCA) procedures.
Medtronic reports more than 800,000 such procedures in the U.S. each year, with stents used in about 70% of these cases. Of that figure, about 20% of these procedures involve treating small vessels of less than 3 mm. The annual worldwide market for stents is estimated at greater than $2 billion. Medtronic AVE's S670 and the D1 balloon catheter are components of a system that includes guiding catheters (Zuma and Z2), steerable guidewires (GT1 and Hyperflex), balloon dilatation catheters, and accessories for angioplasty procedures.
In other company news, Medtronic received CE Mark approval, and has begun introduction in select international markets, for its BeStent2 with Discrete Technology rapid exchange coronary stent delivery system. A laser-cut stent, the BeStent2 is used after coronary arteries have been opened via PTCA. The system is designed to improve scaffolding, radiopacity, and deliverability while providing customers with another choice of product to treat coronary artery disease. It is available in 3.0 mm, 3.5 mm, and 4.0 mm diameters and 9 mm, 12 mm, 15 mm, 18 mm, 24 mm and 30 mm lengths.
Elsewhere in the product pipeline:
Actelion (Allschwil, Switzerland) reported positive results of its Phase III clinical trial in pulmonary hypertension. According to the company, treatment with its new compound, Bosentan, an endothelin antagonist, significantly improved hemodynamics and increased the exercise capacity of the patients in a randomized, placebo-controlled, double-blind study involving 32 patients. The new compound targets the endothelium, a single layer of cells forming an interface between blood and the surrounding tissue maintaining the tone of the blood vessels. The endothelium produces active compounds such as endothelin, one of the most powerful constrictors of blood vessels. An abnormal stimulation of endothelin plays a major role in the progression of several diseases of the heart. Bosentan also is in Phase III trials in chronic heart failure.
Aventis Pharmaceuticals (Parsippany, New Jersey), the U.S. pharmaceutical company of Aventis SA, said it received a non-approvable letter from the FDA concerning Refludan for anticoagulation in adults with acute coronary syndrome. The action follows the recommendation of the FDA's Cardiovascular and Renal Drugs Advisory Committee in early May. Aventis said it will discuss with the FDA its next steps for the drug in this indication. Refludan will remain on the market to treat heparin-induced thrombocytopenia Type II and associated thromboembolic disease in order to prevent further thromboembolic complications.
Avant Immunotherapeutics (Needham, Massachusetts) said results of a Phase I/II study of TP10 in infants undergoing cardiac surgery suggest the drug was well tolerated with no adverse events attributed to study treatment. The inhibitor was studied in 15 infants. Avant plans to refine the TP10 dosing regimen in a Phase IIb study this year prior to starting the pivotal Phase III study early next year.
Cardima (Fremont, California) said the U.S. Phase I and II trial results of its Revelation catheter for treating atrial fibrillation (AF) were better than those obtained in Europe. In Europe, 78% of the patients in the trial experienced either an elimination of AF episodes or a greater than 80% reduction in them, resulting in CE Mark in 1998. Interim results of the first two phases of the U.S. trial were presented during the annual meeting of the North American Society for Pacing and Electrophysiology in Washington. Cardima said it believes it is the only company with an ongoing clinical trial submission for right-sided linear ablation treatment of AF with microcatheters in process with the FDA. Phil Radlick, PhD, president and chief executive officer of Cardima, said that, with 80 patients treated in the U.S., "we should soon be entering the final phase of this trial using the Revelation Tx microcatheter
We are pleased with the results and also, that so far, they appear to be well within the guidelines suggested by the FDA Circulatory System Devices Advisory Panel."
Centocor (Malvern, Pennsylvania) and Eli Lilly and Co. (Indianapolis, Indiana) said they completed patient enrollment of the Phase III trial investigating the use of ReoPro (abciximab) as primary drug therapy for patients with unstable angina. ReoPro is approved for use in patients with refractory unstable angina when a balloon or stent procedure is planned within 24 hours.
A landmark randomized clinical trial using a catheter-based, gamma radiation (Iridium-192) ribbon for reduction of in-stent restenosis indicates this therapy is clinically effective and may be highly cost-effective by the end of the first year after treatment. Titled Gamma-1, the study was funded by Cordis (Miami Lakes, Florida), a unit of Johnson & Johnson (New Brunswick, New Jersey), using gamma-ribbon radiation therapy licensed from Best Medical (Springfield, Virginia). Conducted at 12 U.S. sites, the study included 252 patients with native coronary artery disease and in-stent restenosis. The Cordis Checkmate Gamma Radiation System employed in this study featured a closed-end lumen catheter accommodating a 0.03 inch diameter ribbon with 6, 10, or 14 seeds of Ir-192 to treat lesions up to 45 mm in length. A cost-effectiveness study assessment was done by David Cohen, MD, of Beth Israel Deaconess Medical Center (Boston, Massachusetts), who said the treatment "was not only highly effective clinically, but also has the potential to be a very cost-effective treatment."
Corgenix Medical (Denver, Colorado) received FDA clearance to market its product for the laboratory diagnosis and risk assessment of blood clotting disorders. The new test detects IgA antibodies to phosphatidylserine, with high levels of these antibodies reported in patients with antiphospholipid syndrome and characterized by recurrent thrombosis, thrombocytopenia, and fetal loss. This test complements two Corgenix products previously cleared by the FDA, the IgG and the IgM anti-phosphatidylserine test kits. Two additional test kits to detect IgG and IgM antibodies to prothrombin have recently been submitted to the FDA. These antibodies to a coagulation protein are useful for the comprehensive laboratory evaluation of thrombosis and represent a step forward in the diagnosis and management of blood clotting disease.
EndoSonics (Rancho Cordova, California) said it has received approval from the FDA of its investigational device exemption application to begin human clinical trials of its directional radiation (brachytherapy) device to advance the treatment of cardiovascular disease. Named BRIGADE (Beta Radiation with IVUS Guidance and Directed Energy), the device was developed in conjunction with the Cleveland Clinic Foundation (Cleveland, Ohio), with Patrick Whitlow, MD, the clinic's director of interventional cardiology, as principal investigator. The trial is the first to target diabetic patients who have shown a 60% to 70% restenosis rate in the types of blockages to be investigated. It features direct radiation dosing to analyze IVUS-guided radiation.
Gensia Sicor Pharmaceuticals, a wholly owned subsidiary of Sicor (Irvine, California), received tentative approval of an abbreviated new drug application for Enalaprilat injection, a drug indicated for the treatment of hypertension.
Guidant (Indianapolis, Indiana) said its Galileo Intravascular Radiotherapy System – an automated treatment designed to reduce or minimize reoccurring blockages – has received CE mark approval and is commercially available in most European countries, and in others that base regulatory clearance on the CE mark. The Galileo system features automated radiation source delivery and storage and automated dose calculation; a catheter that centers the radioactive source within the artery lumen for even dose delivery; and continual dose perfusion through the artery when the centering catheter balloon is inflated. The study was conducted at multiple sites in the U.S., Europe, and Singapore. While the Galileo system has received CE Mark approval, it is currently limited to investigational use in the U.S. The company is currently conducting and/or collaborating on four additional radiation-specific clinical trials and has plans to begin four more. Guidant also received the CE mark for its Multi-Link Tetra Coronary Stent System, which incorporates new technologies for improved delivery and implant performance. The Tetra is a fourth-generation stent based on the company's Multi-Link Coronary Stent design.
Interventional Technologies' (San Diego, California) Cutting Balloon microsurgical dilation catheter system has received FDA premarket approval for treatment of coronary artery disease. The company terms the Cutting Balloon "the most significant improvement in balloon angioplasty since angioplasty was introduced more than 20 years ago." The system features microsurgical blades mounted longitudinally on an angioplasty balloon to open narrowed arteries with more precision and less trauma than conventional angioplasty. Internationally, more than 70,000 patients have been treated with the procedure, and studies have reported significant advantages over conventional angioplasty in terms of restenosis and the need for repeat interventions. Robert Reiss, company chairman and CEO, said that FDA approval "concludes a nine-year pioneering effort on our part to provide a truly revolutionary product to the U.S. cardiology community."
Medical Scientists (MSI; Boston Massachusetts), has developed the MediSave CAD (coronary artery disease) software, calling it "the next generation, and future of population-based healthcare decision-making." The software allows health care professionals to forecast disease-specific medical costs for a population, without the need for complicated medical claims data. Developed in partnership with March FIRST (formerly Whittman-Hart; Chicago, Illinois), the CAD model will be incorporated into the company's MediSave platform, which predicts both population-specific medical and nonmedical costs associated with a specific disease, and the potential impact of future disease management or pharmacy upon the specific population.
The Medicines Co. (Cambridge, Massachusetts) has received an approval letter from the FDA for the use of Angiomax (bivalirudin) as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty. "This is a good step forward and we're pleased," said Clive Meanwell, CEO. "It's been a combination of a lot of work by us, the agency, and experts. It's quite nice to see progress." Final approval is dependent upon the satisfaction of conditions specified by the agency. The private company also is developing the product for other indications and has a 17,000-patient Phase III trial under way to study the use of Angiomax in patients who are hospitalized for myocardial infarction. This worldwide trial, which is enrolling 200 patients a week, is projected to end early next year. In addition, a Phase III trial is ongoing for patients undergoing angioplasty who have experienced heparin-induced thrombocytopenia or heparin-induced thrombocytopenia and thrombosis syndrome. A Phase III program to evaluate Angiomax in patients with unstable angina is planned for next year. Formerly called Hirulog, Angiomax has had a difficult journey on its road to FDA approval. Biogen (also Cambridge) conducted Phase III studies that were designed to show that Hirulog provided a 33% reduction in deaths and myocardial infarction following angioplasty compared to heparin, while providing significant reduction in hemorrhages. However, the anticoagulant showed no statistical difference between Hirulog and heparin in procedural failures that included death, myocardial infarction, abrupt vessel closure, and additional revascularization procedures. Subsequently, Biogen abandoned the drug's development. The Medicines Co. bought the rights to Hirulog from Biogen in 1997, and filed a new drug application for the drug in February 1998.
Meridian Medical Technologies (Columbia, Maryland) reported on a study, published in the American Journal of Cardiology, demonstrating the superiority of its Prime ECG electrocardiac mapping system over traditional ECG systems in detecting complications of heart attacks that put patients at increased risk for more extensive heart damage and possible death without appropriate treatment. "European studies in more than 3,000 patients have shown that the Prime ECG provides dramatically improved precision that has the potential to save lives through the early diagnosis and treatment of heart attacks," said James Miller, chairman, president, and CEO. The new study included 479 patients with acute ischemic chest pain, 173 with confirmed acute myocardial infarction (AMI), and 62 classified as inferior AMI (lower region of the heart). In evaluating those patients with inferior AMI, the Prime ECG system was found 38% more effective at locating right ventricular involvement and 13.5 times more effective at detecting posterior wall involvement than a traditional 12-lead ECG system. The system features a powerful computer and proprietary software to process and display results in a range of full-color images. Meridian said that, following completion of ongoing U.S. clinical trials, it will make an FDA submission for market approval.
Protherics plc (Cheshire, United Kingdom) said its angiotensin vaccine, under development to treat high blood pressure, has completed Phase I trials and demonstrated its ability to raise an antibody response in humans. Results also demonstrated the antibodies are capable of blocking the blood pressure raising effects of angiotensin.
Raytel Medical (San Mateo, California) and St. Jude Medical (St. Paul, Minnesota) reported successful testing of Housecall, the first commercial system for remotely monitoring an implanted cardioverter defibrillator (ICD). Results from the test demonstrated the efficiency and ease of use of the Housecall system. With a conventional telephone, the 25 patients using the system were able to download and relay all information stored in the memory of their ICDs in under 1 minute. Raytel technicians received the information, summarized the tests, interpreted the data and forwarded it to the doctor's office or clinic. Housecall features the ability to furnish data on recent episodes of tachyarrhythmia, including tachyarrhythmic episodes, the date and time of specific events, and stored intracardiac electrograms relating to such episodes. For post-shock or symptomatic calls, patients telephone an 800 number for the Raytel Cardiac Services monitoring center and then, following instructions, place the transmitter's wand over the implanted device. Raytel technicians gather and interpret information on the ICD device and how it is currently functioning as well as obtain current information on how the device and patient are interacting. A study using the Housecall system will be conducted at the Cleveland Clinic (Cleveland, Ohio).
Somanetics (Troy, Michigan) said a 156-patient study demonstrated that cardiac surgery patients with low regional brain blood oxygen saturation before their surgery, as monitored by the firm's INVOS Cerebral Oximeter, are more likely to suffer post-operative frontal lobe and cognitive dysfunction after their surgery than patients with higher brain oxygen saturation before their surgery. Conducted at Cornell University's Weill Medical College (New York), the study also demonstrated that low regional brain blood oxygen saturation before cardiac surgery is associated with prolonged intensive care and overall hospital stays. The INVOS is the only commercially-available patient monitoring system which non-invasively and continuously monitors changes in the regional blood oxygen saturation in the adult brain, according to Somanetics. The cerebral oximeter noninvasively transmits and detects visible and near-infrared light through SomaSensors, single-use sensors placed on both sides of a patient's forehead, and its measurements can help to prevent or reduce neurological injuries related to surgery and other critical care situations.
St. Jude Medical (St. Paul, Minnesota) reported the first implants of its new Integrity AFx pacemaker system in late April at the Mustamae Hospital (Tallinn, Estonia). Hasso Uuetoa, MD, implanted a dual-chamber rate-responsive Integrity AFx DR AutoCapture Pacing System in a 76-year-old male patient with complete heart block. The same day, department head Juri Voitk, MD, implanted an Integrity AFx DR pacemaker in a 66-year-old male patient with complete heart block and recently documented episodes of atrial fibrillation (AF). Both patients are doing well and the pacemakers are performing appropriately, according to the company. The Integrity AFx incorporates St. Jude's Dynamic Atrial Overdrive (DAO) algorithm for the suppression of AF, along with the company's Beat-by-Beat AutoCapture Pacing System. The DAO algorithm uses a patient-tailored rate to overdrive the atrium and suppress AF before it starts. The algorithm has been available in Europe since June 1999 on the company's Trilogy pacemaker. St. Jude said it expects to launch the Integrity AFx system in 2Q00.
Thoratec Laboratories (Pleasanton, California) received FDA approval of an investigational device exemption for its Aria CABG (coronary artery bypass graft) and said it would initiate patient enrollment in the AEGIS/US (AlternativE Graft Investigational Study) in 2Q00. The study will test the effectiveness of the Aria CABG in coronary artery bypass patients who have too few or no suitable vessels of their own. Enrolled patients are expected to be followed for one year after receiving one or more Aria grafts randomized against their own marginal quality veins as a control. The company's AEGIS/Canada clinical program has been under way since late last year. "This is a major development in the realization of Thoratec's growth strategy," said D. Keith Grossman, president and CEO. "We are the first company ever to gain approval to enter U.S. clinical trials for a prosthetic aorta-to-coronary artery bypass graft for these patients." While the study design calls for enrolled patients to be assessed at one year for graft patency as determined by angiography, the first 20 of the approved 30 Phase I patients will be assessed by myocardial perfusion imaging at only two months after implant. Using this two-month data, Thoratec will then file an amendment to the approved IDE for the remaining patient enrollment at up to 15 centers.
The Vitatron (Dieren, the Netherlands) organization of Medtronic reported the commercial release outside the U.S. of three new products to treat atrial fibrillation (AF). Vitatron PreventAF, Vitatron DiagnoseAF, and Vitatron SelectionAF2.0 software are now available in most European countries and in others that base regulatory clearance on the European CE mark. The Vitatron Prevent AF cardiac stimulator feature four pacing functions designed to prevent atrial fibrillation episodes by suppressing their onset. The Vitatron DiagnoseAF system combines state-of-the art pacemaker functions, including fast mode switching and dual-sensor rate response technology, with atrial fibrillation-focused diagnostic capabilities to aid in identifying and managing AF. The Vitatron Selection AF2.0 software is a noninvasive upgrade for patients who have the Vitatron Selection 900 implantable pacemaker.