June 2002 Part 2: Clinical and Industry News

Anti-clot Drug Powerless During Some Heart Attacks The drug t-PA proved ineffective when given during cardiac arrests in which patients had no pulse, according to a study. We found no evidence that the administration of t-PA during CPR improved the likelihood of either survival to hospital discharge or a return of spontaneous circulation, researchers concluded. The findings do not apply to t-PA’s use in other types of heart attacks, where its effectiveness is well documented. Out-of-hospital cardiac arrest results in some 250,000 deaths annually in the United States and Canada. The study was financed by Hoffmann-LaRoche, whose parent company, Roche Holding Ltd., owns 58 percent of Genentech Inc., the maker of t-PA. Although it is still possible that t-PA might be effective in some circumstance, researchers said, the new findings of Dr. Riyad B. Abu-Laban of the University of British Columbia in Vancouver offer little reason for optimism regarding this therapeutic approach in cases of cardiac arrest. The Abu-Laban team arranged to have t-PA or a placebo given to 233 patients who were getting CPR because of pulseless electrical activity, where only a small amount of blood is being pumped and 96 percent of patients never survive to be discharged from the hospital. It is found in 20 percent of the people with cardiac arrest. Although the researchers found that the heart seemed to resume normal pumping in 21.4 percent of the t-PA recipients, the success rate was essentially the same 23.3 percent for the patients who received the placebo. Ultimately, only one person, a t-PA recipient, survived to be discharged from the hospital. Boston Scientific Announces Final Results of Its TAXUS III Paclitaxel-Eluting Stent Clinical Trial Boston Scientific Corporation has announced the final, six-month results of its TAXUS III paclitaxel-eluting stent clinical trial. TAXUS III is a single-arm registry examining the feasibility of implanting up to two paclitaxel-eluting stents for the treatment of in-stent restenosis. The trial’s main focus is safety, and the primary endpoint is 30-day MACE (Major Adverse Cardiac Events; including death, myocardial infarction and revascularization). This group represents patients with complex vascular disease having recurrent occlusion in a stent, who tend to have an increased probability of restenosis. The trial enrolled 30 patients. Twenty-eight were included in the follow-up analysis; 25 of whom completed quantitative coronary angiographic analysis. The cumulative MACE data for patients out to 10 months reported six target lesion revascularizations (TLRs), one coronary artery bypass graft, and one peri-procedural, non-Q-wave myocardial infarction. There were no stent thromboses and no deaths. The pattern of TLRs was revealing. There were: two restenoses occurring in a segment (gap) between two paclitaxel-eluting stents, two TLRs performed that did not meet angiographic criteria for revascularization and instead were performed to improve stent apposition to the wall evident at initial implant, one restenosis in a bare stent adjacent to two paclitaxel-eluting stents, and one symptom-driven TLR. Quantitative coronary angiographic analysis of stented segments, including the distal and proximal edges, yielded an overall binary restenosis rate of 16 percent (4 of 25). Three of the four reflect restenosis in vessel segments not covered by a paclitaxel-eluting stent. Actual performance within the paclitaxel-eluting stent yields a restenosis rate of four percent (1 of 25). The TAXUS program is a series of clinical studies designed to collect data on Boston Scientific’s proprietary paclitaxel-eluting stent technology for reducing coronary restenosis, the growth of tissue within an artery after angioplasty and stenting. Paclitaxel, the active component of the popular chemotherapeutic agent Taxol®, has demonstrated promising results in pre-clinical and clinical studies for reducing the processes leading to restenosis. The program positions Boston Scientific to launch paclitaxel-eluting stents in Europe this year and in the United States in 2003. The TAXUS I trial confirmed safety and reported zero thrombosis and zero restenosis. The TAXUS II trial completed enrollment of 537 patients in January, and the patients are now in the follow-up period. Preliminary safety data from TAXUS II presented in March at the American College of Cardiology annual meeting provided further support for the safety of paclitaxel-eluting stents. TAXUS IV has enrolled nearly 1,000 of its expected 1,172 patients. It is using the Express stent, a laser-cut, balloon-expandable stent developed exclusively by Boston Scientific. SIRIUS Study 400 Patients Preliminary Results of Large-Scale U.S. Study Support Excellent Results with Cordis’ CYPHER Sirolimus-eluting Stent Clinical investigators reported preliminary findings at The Paris Course on Revascularization (PCR) documenting the excellent results of the CYPHER Sirolimus-eluting Stent in the first 400 patients enrolled in the landmark SIRIUS study. SIRIUS is a large-scale, randomized, double-blind, controlled clinical trial involving 53 U.S. treatment centers and 1,101 patients. The study was sponsored by Cordis Corporation, a Johnson & Johnson company. Eight-month angiographic follow-up showed virtually no in-stent late lumen loss (0.14 mm) in patients treated with the CYPHER Stent, mirroring the 6-month findings of the RAVEL study and the 2-year findings of the First-in-Man study. The 2% rate of angiographic in-stent restenosis representing a 94% reduction versus the control arm (bare metal stent) supports the findings of earlier studies. SIRIUS Co-Principal Investigator Dr. Moses explained one of the major objectives of the SIRIUS study is to evaluate the performance of the CYPHER Sirolimus-eluting Stent across a broad spectrum of patient profiles, including seriously ill patients. Dr. Moses noted that at 9-month clinical follow-up, there was a 72% reduction in target lesion revascularization (TLR) rate in the treatment arm versus the control. The TLR cases in the CYPHER Stent treatment group were almost exclusively due to disease at the stent margins, even though this phenomenon was considerably less frequent in the CYPHER Stent group than in the control group. SIRIUS investigators report excellent safety results for the CYPHER Sirolimus-eluting Stent. At 9-month follow-up, the event-free survival rate was 90.8% in the sirolimus-treated cohort versus 80.6% in the control group (p=0.009). There were no cases of acute, subacute, or late thrombosis in the sirolimus-eluting stent arm of the study, despite only 3 months of anti-platelet therapy and the placement of overlapping stents in a significant number of patients (27%). The CYPHER Sirolimus-eluting Stent, which is an investigational device in the U.S., received CE Mark approval in April and is now available in Europe. Cordis licensed the drug, sirolimus**, from Wyeth Pharmaceuticals for delivery of the drug via a stent. Cordis chose sirolimus for its cytostatic, rather than cytotoxic, properties, thereby inhibiting cell proliferation (cytostatic), rather than killing the cells (cytotoxic). * RAVEL (RAndomized Study with the Sirolimus-eluting VELocity Balloon-Expandable Stent), which was initiated in 2001, involves 238 patients at 19 centers in Europe and Latin America. ** Sirolimus, the active drug released from the stent, is a naturally occurring antibiotic marketed by Wyeth Pharmaceuticals, a unit of Wyeth, under the name Rapamune and used to prevent renal transplant rejection. Cordis has entered into an exclusive worldwide license agreement with Wyeth for delivery of sirolimus via a stent. Rapamune is a trademark of Wyeth Pharmaceuticals. Note: The CYPHER Sirolimus-eluting Stent is an investigational device limited by federal (U.S.) law to investigational use in the United States.