Centocor, Inc. And Eli Lilly and Company Halt Phase 3 Trial Of Reopro For Stroke
HORSHAM, Pa. and INDIANAPOLIS, Oct. 28 /PRNewswire/ -- Centocor, Inc. and Eli Lilly and Company announced today that patient enrollment in the Phase 3 trial of REOPRO® (abciximab) for the treatment of acute ischemic stroke has been permanently discontinued. Based on careful review of the data and the observed benefit-risk profile, the trial's independent Safety and Efficacy Monitoring Committee (SEMC) for the Abciximab in Emergent Stroke Treatment Trial-II (AbESTT-II) recommended that the study not resume enrollment. After reviewing these recommendations, the principal investigators, the AbESTT-II Executive Committee and both Companies have unanimously agreed with the SEMC, and, effective immediately, permanently discontinued enrollment in the trial.
"Patient safety is paramount to all of our drug development programs, so we have taken the prudent step of ending the AbESTT-II trial," said Jerome A. Boscia, M.D., senior vice president, Clinical R&D, Centocor, Inc. "While there are no guarantees that every clinical study will succeed, Centocor and Lilly maintain their R&D commitments to researching and developing safe, effective therapies for patients in need."
On October 4, 2005, Centocor and Lilly announced that enrollment in AbESTT-II had been temporarily suspended following a recommendation from the SEMC based on an observed safety concern in the data that it had reviewed. The new recommendation comes after the SEMC reviewed additional efficacy and safety data on most of the 808 enrolled patients to help determine if the benefit-risk profile warranted continuing the study. All outstanding follow- up evaluations and data from patients who have been enrolled will continue to be collected as quickly as possible and general unblinding of the trial will occur once the database is locked, which is expected to occur next year.
REOPRO is approved in the United States and many other countries around the world as an adjunct to percutaneous coronary intervention (PCI) for the prevention of cardiac ischemic complications in patients undergoing PCI and in patients with unstable angina not responding to conventional medical therapy when PCI is planned within 24 hours. The companies clearly reiterated that they are not aware of any new data that change the favorable product profile of REOPRO in approved indications - indications that are supported by more than 14 randomized clinical trials and a decade of clinical experience. REOPRO is not indicated in patients having an acute ischemic stroke.
AbESTT-II was a Phase 3, multinational, multicenter, randomized, double- blind placebo-controlled study evaluating the safety and efficacy of REOPRO in improving neurological function and minimizing disability in patients who have had an acute ischemic stroke. Preliminary results from other trials suggested that REOPRO might have been useful in the treatment of stroke beyond the three-hour time window in which the only currently approved therapy is used to dissolve blood clots in ischemic stroke patients. Most stroke patients do not arrive in the emergency department within three hours of symptom onset. The trial evaluated two populations: patients randomized within 4.5 hours with planned treatment within five hours of stroke onset (primary analysis population, n=1200) and a companion population of patients randomized 4.5-5.5 hours after stroke onset with planned treatment within six hours or who awaken with stroke symptoms and can be randomized within 2.5 hours of awakening (n=600). In May 2005, treatment of the small segment of patients awakening after having suffered a stroke was stopped because of an increased risk of intracranial hemorrhage in that population. At that time, the SEMC recommended continuing enrollment with the remaining groups being evaluated in the trial.
Approximately 150 clinical trial sites participated in the AbESTT-II worldwide trial, which began in 2003. The goal for enrollment was 1,800 participants.
About Acute Ischemic Stroke
Acute stroke occurs when a blood vessel becomes blocked in the brain. This blockage prevents oxygen and nutrients in the blood from getting to part of the brain, resulting in the death of that part of the brain. Approximately 85 percent of all strokes are termed ischemic, meaning they are caused by a blood clot or plaque that blocks a blood vessel in the brain. Stroke is the third leading cause of death in the United States, resulting in more than 150,000 deaths every year.
Important Safety Information
REOPRO has the potential to increase the risk of bleeding, particularly in the presence of anticoagulation agents, e.g., from heparin or other anticoagulants or thrombolytics. The risk of a major bleed due to REOPRO therapy is increased in patients receiving thrombolytics and should be weighed against the anticipated benefits.
Guidelines for reduction of bleeding include: use of a low-dose, weight- adjusted heparin regimen, discontinuation of heparin on completion of the procedure with removal of the arterial sheath within 6 hours, careful vascular access site management and careful patient management, including attention to other potential bleeding sites, use of a weight-adjusted bolus and continuous- infusion dose of REOPRO.
In clinical trials, patients treated with REOPRO were more likely than patients who received placebo to experience decreases in platelet counts, including severe thrombocytopenia (also see readministration below).
Administration of REOPRO may result in the formation of human anti chimeric antibodies (HACA) that could potentially cause allergic or hypersensitivity reactions (including anaphylaxis), thrombocytopenia, or diminished benefit upon readministration. In a registry study of REOPRO readministration (1342 treatments in 1286 patients), there were no reports of serious allergic reactions or anaphylaxis. Thrombocytopenia was observed at higher rates in the readministration study than in the phase III studies of first-time administration, suggesting that readministration may be associated with an increased incidence and severity of thrombocytopenia. This increased risk was associated with a history of thrombocytopenia on prior REOPRO exposure, a positive HACA assay at baseline, and readministration within 30 days.
Rare cases of anaphylaxis in patients treated with REOPRO have been reported in post-marketing adverse event reporting. If anaphylaxis occurs, administration of REOPRO should be discontinued immediately and appropriate resuscitative measures should be initiated.
Because REOPRO may increase the risk of bleeding, use is contraindicated in the following clinical situations: active internal bleeding, recent (within 6 weeks) gastrointestinal (GI) or genitourinary (GU) bleeding of clinical significance, history of cerebrovascular accident (CVA) within 2 years, or CVA with a significant residual neurological deficit, bleeding diathesis, administration of oral anticoagulants within 7 days unless prothrombin time is less than or equal to 1.2 times control, thrombocytopenia (<100,000 cells/microliter), recent (within 6 weeks) major surgery or trauma, intracranial neoplasm, arteriovenous malformation, or aneurysm, severe uncontrolled hypertension, presumed or documented history of vasculitis, use of intravenous dextran before percutaneous coronary intervention, or intent to use it during intervention, known hypersensitivity to any component of this product or to murine proteins.
REOPRO was developed by Centocor of Malvern, Pa., USA, and is manufactured by Centocor, B.V., in Leiden, the Netherlands. Eli Lilly and Company markets and distributes the product worldwide except in Japan.
Centocor is a leading biopharmaceutical company that creates, acquires and markets cost-effective therapies that yield long-term benefits for patients and the healthcare community. The company is dedicated to the research and development of treatments for a wide range of diseases including cancer, infectious diseases, cardiovascular and metabolic diseases and Immune-Mediated Inflammatory Disorders (I.M.I.D.), such as arthritis and inflammatory skin diseases. Centocor's products, developed primarily through monoclonal antibody technology, help physicians deliver innovative treatments to improve human health and restore patients' quality of life. Centocor is a wholly owned subsidiary of Johnson & Johnson, the worldwide manufacturer of healthcare products.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs. Additional information about Lilly is available at http://www.lilly.com.
ReoPro® (abciximab, Centocor), Lilly-------------------------------------------------------------------------------- Source: Centocor, Inc.