Clinical and Industry News

Early Results Suggest PolarCath System May Be Better Than Conventional Angioplasty Balloon The PolarCath System which uses a new form of angioplasty to open blocked arteries by cooling and dilating them appears to be more successful and result in fewer complications than conventional balloon angioplasty. Early multicenter results using the PolarCath Peripheral Transluminal Angioplasty System to treat blocked leg arteries were presented at the International Symposium on Endovascular Therapy (ISET). At nine months, 85 percent of the treated lesions remained patent, which is significantly better than expected patency rates for either angioplasty or stenting, said John Laird, MD, director of peripheral vascular intervention at Washington Hospital Center, Washington, D.C. and principal investigator of the study. In addition, significant dissection occurred acutely in only 6 percent of the patients, which is less than half of the dissection rates reported for conventional angioplasty. Although it is early, these results look promising, and may demonstrate improved, long-term outcomes compared to conventional therapies. The PolarCath System involves the same minimally invasive approach to treatment as balloon angioplasty. PolarCath, however, has a specially designed balloon system that is advanced to the site of the blockage and filled with liquid nitrous oxide, which evaporates into a gas upon entering the balloon. The evaporation process cools the balloon to specific sub-freezing temperatures, thereby cooling the plaque and vessel wall as it dilates the vessel. This is believed to crack the plaque and aid in reshaping it with minimal injury to the vessel wall, and consequently with minimal inflammation. To date, more than 250 patients have been treated with the PolarCath System for blockages of blood vessels in the legs with promising results. A study conducted to evaluate the safety and effectiveness of the new device has been underway for more than a year. The multicenter study involves 15 sites in the United States and one site in Germany. In 71 patients followed up at three months after the therapy, 100 percent of the treated blockages remained open. In 46 patients followed up at six months, 41 (89 percent) of the blockages remained open; and in 26 patients followed up at nine months, 22 (85%) of the blockages remained open. In addition, six of 102 patients (6%) had significant dissections (Grade C and D) after being treated with the PolarCath System, compared to an expected range of 12“43% for traditional angioplasty. The final study results are expected this summer. The PolarCath Peripheral Transluminal Angioplasty System received marketing clearance from the U.S. FDA last September, and will be commercially available in the U.S. this year. The device has been available in Europe since last year. The system was developed by CryoVascular Systems. For more information, visit www.cryoinc.com. JCAHO Issues National Alert About Infection Control Deaths, Encourages Greater Reporting A bulletin issued by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) advises that the deaths of patients from hospital-acquired infections are being seriously underreported across America. The Sentinel Event Alert, sent to nearly 17,000 JCAHO-accredited health care facilities, also urges compliance with new guidelines from the Centers for Disease Control and Prevention that advise health care professionals to use alcohol-based handrubs in conjunction with traditional soap and water and sterile gloves to prevent these acquired infections. The CDC estimates that more than two million patients annually develop infections while hospitalized for other health problems and that nearly 90,000 die as a result of these infections. Despite these high figures, the Joint Commission’s 7-year-old patient safety reporting database includes only 10 such reports that cover 53 patients. We are receiving a disproportionately low volume of reports on the number of patient deaths from infections acquired in the health care setting, possibly because many health care organizations do not view these events as ‘errors’ under the definition of a sentinel event, says Dennis S. O’Leary, MD, president, JCAHO. We are urging health care organizations to share this information with the Joint Commission, just as they might share information about other types of sentinel events with us. Because of the nature of these events, the Joint Commission believes it is likely that health care facilities will have already conducted the related in-depth analyses required as part of the accreditation standards. Increased reporting will lead to greater understanding of the factors that lead to their occurrence and effective strategies for prevention, according to the JCAHO alert. Meanwhile, the Joint Commission is intensifying its attention to infection control practices as part of its continuing on-site surveillance of accredited organizations. The Joint Commission is also convening a new infection control expert panel to suggest ways in which current JCAHO standards can be strengthened. The new warning about infections acquired in health care settings is the latest in a series of patient safety alerts issued by the Joint Commission. Previous alerts have focused on wrong-site surgery, deadly medication mix-ups, patient suicides, infant abductions and fatal falls among the elderly, among others. The complete list and text of past issues of Sentinel Event Alert can be found on JCAHO’s website at www.jcaho.org. LACI Pivotal Study Primary Endpoint Indicates 93 Percent Six-Month Survival With Limb Salvage Significant Adverse Events in LACI-Treated Patients Nearly Half That of Control Group Data from the Spectranetics Corporation’s LACI (Laser Angioplasty to treat Critical Limb Ischemia) pivotal Phase II clinical trial was presented at the Interventional Symposium on Endovascular Therapy (ISET) underway in Miami Beach, Florida. The results were presented by John R. Laird, MD, of the Washington Hospital Center in Washington, D.C. and principal investigator of the LACI trial. Study data showed that six-month survival with limb salvage, which is the primary clinical endpoint of the study, was achieved in 93% of the limbs treated compared with 87% in the control group. Additionally, significant adverse events in treated patients were nearly one-half that of the control group at 33% and 60%, respectively. The trial enrolled 145 patients (155 limbs) at 14 domestic and several European sites. The control group was comprised of 789 patients with critical limb ischemia treated with a variety of standard therapies. The successful treatment of critical limb ischemia is measured by the relief of rest pain, the healing of ulcers and the avoidance of major amputations, said Dr. Laird. We are impressed with the improved limb salvage rate and the greatly reduced incidence of significant adverse events when using the Spectranetics excimer laser to treat this challenging patient group, which included diabetics and patients with hypertension and coronary artery disease. The LACI Phase II trial enrolled patients who were considered to be poor surgical candidates with circulatory problems of the lower leg evidenced by leg pain, even while resting; non-healing ulcers on the foot or lower leg; or areas of dead, gangrenous tissue on the foot or lower leg that require minor amputation (Rutherford categories 4, 5 and 6). Enrollment began in April 2001 and was completed in April 2002. The trial included the use of coronary catheters as well as larger diameter catheters ranging from 2.2 to 2.5 millimeters. The full slideshow of LACI data presented will be available at www.spectranetics.com/co/news.html. Positive Results From Phase II Trial On MC-1 Medicure Inc., a cardiovascular biotechnology company, announced positive results with treatment from its lead compound MC-1 in the recently completed Phase II MEND-1 clinical study managed by the Duke Clinical Research Institute (DCRI) in Durham, North Carolina. Both the primary and secondary endpoints of the Phase II MEND-1 study were met. The primary endpoint of the trial was infarct size during the procedure as determined by the release of the amount of the marker cardiac enzyme, CK-MB, over 24 hours following percutaneous coronary intervention (PCI). Improvement was also shown in certain secondary endpoints, including myocardial ischemia measured by continuous ST-segment electrocardiographic monitoring, peak periprocedural CK- MB through 24 hours and clinical tolerability and safety. The Phase II trial was an investigation of the cardioprotective effects of MC-1 in mitigating damage caused by ischemia and ischemic reperfusion in heart disease patients undergoing angioplasty. MEND-1 was a randomized, placebo-controlled, blinded study, which evaluated the extent of damage to the heart muscle following elective PCI in 60 high risk patients at increased risk for cardiac damage. Damage to the heart was assessed by quantifying the release of the cardiac enzyme CK-MB, commonly used to diagnose myocardial infarct. Treatment with MC-1 reduced the release of CK-MB following PCI. The full results from the Phase II clinical study will be presented by Dr. James E. Tcheng. MD, FACC, Associate Professor of Medicine, Duke University Medical Center in connection with the Annual Meeting of the American College of Cardiology in Chicago, March 30-April 2, 2003. AtheroGenics to Initiate Phase III Clinical Trial with AGI-1067 in Atherosclerosis Study to Directly Target Link Between Inflammation and Heart Disease AtheroGenics, Inc., a pharmaceutical company focused on the treatment of chronic inflammatory diseases, is proceeding with the initiation of a pivotal Phase III clinical trial with its oral anti-inflammatory drug candidate, AGI-1067, for the treatment of atherosclerosis in patients with coronary heart disease (CHD). The trial will be referred to as ARISE (Aggressive Reduction of Inflammation Stops Events). AGI-1067 is the first in a new class of drugs known as vascular protectants, or v-protectants, that aim to reduce inflammation in blood vessel walls. Positive results from AtheroGenics’ Phase II CART-1 clinical trial (Canadian Antioxidant Restenosis Trial-1) suggested that AGI-1067 had a direct anti-atherosclerotic effect on the coronary blood vessels, which included improvements in lumen volume, plaque volume and total vessel volume. CART-1 also demonstrated that AGI-1067 was well tolerated with no increase in adverse effects versus placebo. The ARISE trial will be conducted in cardiac centers in the United States, Canada and South Africa, and will evaluate the impact of AGI-1067 on outcome measures such as death due to coronary disease, myocardial infarction, stroke, coronary re-vascularization and unstable angina in patients who have CHD. The study will assess the incremental benefits of AGI-1067 over current standard of care in this patient population. As such, all patients in the trial, including those on placebo, will be receiving other appropriate heart disease medications, including statins and other cholesterol-lowering therapies, high blood pressure medications and anti-clotting agents. ARISE will enroll 4,000 patients who will be followed for an average of 18 months or until a minimum of 1,160 primary events have occurred. Boston Scientific Completes Enrollment of TAXUS VI Clinical Trial Angiotech Pharmaceuticals’ corporate partner, Boston Scientific (BSC) announced that it has completed enrollment of its TAXUS VI clinical trial. TAXUS VI is an international trial studying 448 patients with complex coronary artery disease at 44 sites. It is designed to establish the safety and efficacy of the moderate-release formulation in the treatment of longer lesions (greater than or equal to 18 mm in length). The TAXUS VI trial is using the BSC’s internally developed Express stent. The trial which includes the use of multiple stents has a primary endpoint based on nine- month target vessel revascularization. The TAXUS program is a series of clinical studies designed to collect data on Boston Scientific's proprietary polymer-based, paclitaxel-eluting stent technology for reducing coronary restenosis, the growth of neointimal tissue within an artery after angioplasty and stenting. Polymer-based delivery of paclitaxel, at cytostatic doses, has demonstrated promising results in preclinical and clinical studies for reducing the processes leading to restenosis. The Company initiated the TAXUS program in 1997. The TAXUS I trial confirmed safety and reported zero thrombosis and zero restenosis. The TAXUS II trial studied the treatment of de novo coronary lesions and demonstrated both safety and efficacy using the slow- and moderate- release formulations and confirmed safety with no thrombosis. Significant improvements were seen for clinical, angiographic and intravascular measures of stent performance compared with the bare control stent. The TAXUS III trial, which studied the treatment of in-stent restenosis, also confirmed safety with no thrombosis. The TAXUS IV trial has completed enrollment and nine-month follow-up is underway. This study is designed to assess the safety and efficacy of a slow-release formulation to support regulatory filings for U.S. product commercialization. The TAXUS V trial has received conditional approval from the U. S. Food and Drug Administration to enroll patients and will study a higher risk patient population than TAXUS IV, including patients with smaller vessels and longer lesions. Boston Scientific has also initiated a transitional registry program (WISDOM) in a number of countries as part of a limited commercial launch of its TAXUS paclitaxel-eluting stent system. Carbon Monoxide May Aid Arteries Tests on mice and rats indicate that the potentially deadly gas carbon monoxide inhaled at very low concentrations may help arteries damaged in angioplasty and transplants. Scientists say it is too soon to say the therapy would help people. Researchers at the University of Pittsburgh and Harvard Medical School report that exposing rats and mice to low levels of carbon monoxide the poisonous gas emitted from faulty furnaces or cars left running in garages prevents excessive cell growth. Rats and mice that had angioplasty were exposed to the gas for an hour before the procedure, while rats with artery grafts were exposed several weeks after their transplants. The level of exposure was less than 1/25th of what would be considered toxic, a researcher said. The animals suffered no ill effects and experiments are now being done in pigs, the scientists reported. These findings demonstrate a significant protective role for (carbon monoxide) in vascular injury, said Leo Otterbein, an assistant professor at the University of Pittsburgh School of Medicine. Two years ago, David J. Pinsky of Columbia University reported that carbon monoxide could be beneficial to animals that had suffered severe lung injury by helping block the formation of blood clots. Pinsky, who was not part of the new research group, welcomed the work. It is premature to conclude that this therapy would be useful in humans. However, the accumulating evidence certainly argues for rigorous study, Pinsky said. Dr. Augustine M. K. Choi, a member of the Pittsburgh group, agreed on the need for caution. It is exciting that CO at low doses can be beneficial, but we still have a lot of work to do on how to deliver CO safely, he said. Otterbein explained that the idea of using carbon monoxide stemmed from the finding that an enzyme in the body, Heme oxygenase, produces CO. When injuries occur the amount of the enzyme increases, producing more CO. We thought maybe its purpose is to somehow counter the inflammation, he said. Otterbein’s team at Pittsburgh exposed mice and rats to one hour of air containing 250 parts per million of carbon monoxide before a balloon angioplasty was performed. In animals that had breathed only air, artery wall thickening caused by the treatment began to appear at 20 days to 30 days and was significant at 50 days to 60 days. This thickening was reduced by about 70 percent in animals that had been exposed to the gas. The Harvard Medical School group did the transplant experiments, exposing rats to carbon monoxide for 56 days following the surgery. Cell wall thickening was reduced by about 60 percent in the treated animals, Dr. Fritz H. Bach said. Otterbein said the research suggests that the protective effect of carbon monoxide stems from its ability to block the activation and activity of white blood cells, which normally move to the site of an injury and cause the inflammation. It also appears to reduce the proliferation of smooth muscle cells along the arteries.

NULL