Results Published in New England Journal of Medicine Show Angiomax Improved Net Clinical Outcomes and Resulted in Improved Survival Rates in the Most Severe Heart Attack PatientsPARSIPPANY, N.J.--(BUSINESS WIRE)--May 22, 2008 - The Medicines Company (NASDAQ: MDCO) today announced that the New England Journal of Medicine published results from the HORIZONS-AMI trial. According to findings, Angiomax(R) (bivalirudin) significantly improved net clinical adverse events by 24 percent as well as resulted in a reduction in overall mortality by 32 percent and cardiac mortality by 38 percent when compared to heparin plus routine glycoprotein IIb/IIIa inhibitor (GPI) within 30 days following primary angioplasty strategy.(1)
HORIZONS-AMI is the first trial to evaluate Angiomax in patients with ST-segment elevation myocardial infarction (STEMI), the most severe form of heart attack, and one of the largest studies ever to focus on the appropriate use of anticoagulant medications in this population undergoing primary percutaneous coronary intervention (PCI). In the landmark global trial, Angiomax was compared to heparin plus GPI in more than 3,600 patients. Only 7.2 percent of patients in the Angiomax group received provisional GPI.(1) Findings confirm the results of previous clinical trials that show improved outcomes with Angiomax in less severe patient populations undergoing PCI.(2,3)
"The HORIZONS-AMI data show that using bivalirudin instead of heparin with a GPI during angioplasty increased survival in acute heart attack patients, a group who are at high risk for death or disability," said Gregg W. Stone, MD, professor of medicine, Columbia University Medical Center and chairman of the Cardiovascular Research Foundation, which conducted the trial. "As the first multi-center, randomized, primary angioplasty trial in STEMI patients to show improved survival, we expect HORIZONS-AMI to have an immediate impact on the choice of drug therapy during angioplasty for heart attack patients around the world."
Additional findings at 30 days show Angiomax significantly reduced rates of major bleeding by 40 percent and demonstrated comparable rates of major cardiovascular adverse events.(1) Angiomax has previously been shown to result in less bleeding and similar rates of composite ischemia compared to heparin plus GPI in patients undergoing angioplasty for stable angina,(2) unstable angina and non-ST-elevation myocardial infarction (NSTEMI) making Angiomax an attractive treatment option across virtually all patients undergoing PCI.(3)
Dr. Stone emphasized the importance of reducing the risk of bleeding, "In multiple, independent trials, a reduction in bleeding has been shown to be a strong predictor of short and long-term survival in patients undergoing angioplasty."(4)
"We now have two premier trials, HORIZONS-AMI and ACUITY, published in the New England Journal of Medicine, which together demonstrate the benefits of Angiomax across the spectrum of risk in patients treated in the cardiac catheterization lab," said John Kelley, President and Chief Operating Officer of The Medicines Company. "The wealth of data in over 27,000 patients consistently show Angiomax results in comparable rates of ischemia and reduced bleeding at 30 days in patients undergoing PCI, with reduced mortality in the highest risk patients."
HORIZONS-AMI, co-funded by a grant from The Medicines Company and independently run by the Cardiovascular Research Foundation, is a prospective, single-blind, randomized, multi-center study conducted in 11 countries. A total of 3,602 patients undergoing angioplasty were randomly assigned to receive either Angiomax with provisional use of GPI or heparin plus GPI.
The two primary endpoints of the trial were major bleeding and net adverse clinical events, a composite of major adverse cardiovascular events (death, reinfarction, stroke or ischemic target vessel revascularization) or major bleeding at 30 days. The secondary endpoint was major adverse cardiovascular events at 30 days.
About ST-Segment Elevation Myocardial Infarction (STEMI)
STEMI is the most severe type of heart attack and carries a substantial risk of death and disability. STEMI involves myocardial injury, as indicated by significant abnormalities on electrocardiogram (ECG) called ST-segment elevations. Guidelines recommend that STEMI patients be treated with rapid intervention to help prevent further heart damage. According to the American Heart Association (AHA), an estimated 865,000 new and recurrent heart attacks occur every year, of which 400,000 are categorized as STEMI.(5)
STEMI is part of a spectrum of acute coronary syndromes (ACS) caused by acute exacerbation of underlying coronary artery disease; ACS also includes non-ST elevation myocardial infarction (NSTEMI) and unstable angina (UA). NSTEMI is typically caused by partial obstruction of a coronary artery that results in some damage to heart muscle. UA is chest pain at rest or upon exertion, due to ischemia. Stable angina is characterized by predictable chest pain during exertion that resolves at rest, and is not considered a form of ACS. Each year in the United States, about five million people present to the emergency department with chest pain, of which an estimated 1.4 million are identified with ACS.(6)
Angiomax is a direct thrombin inhibitor with a naturally reversible mechanism of action and 25 minute half-life. In clinical trials, treatment with Angiomax resulted in improved clinical outcomes with significantly reduced rates of major bleeding compared to heparin plus GPI across the entire spectrum of risk in patients undergoing PCI and numerically lower rates of 1-year mortality in patients undergoing PCI.
In the United States, Angiomax with provisional GPI is indicated in patients undergoing angioplasty, also called PCI, and in patients with, or at risk of, heparin-induced thrombocytopenia and thrombosis syndrome (HIT/HITTS) undergoing PCI. In addition, Angiomax is indicated for use as an anticoagulant in patients with UA undergoing percutaneous transluminal coronary angioplasty (PTCA). Angiomax is intended for use with aspirin. The most common adverse events for Angiomax in clinical trials comparing Angiomax and heparin were back pain, pain, nausea, headache, and hypotension. The incidence of these adverse events was comparable in both the Angiomax and heparin groups in these trials. An unexplained fall in blood pressure or hematocrit, or any unexplained symptom, should lead to serious consideration of a hemorrhagic event and cessation of Angiomax administration. Angiomax is contraindicated in patients with active major bleeding or hypersensitivity to Angiomax or its components. Please see full prescribing information available at http://www.angiomax.com.
About The Medicines Company
The Medicines Company (NASDAQ: MDCO) is focused on advancing the treatment of critical care patients through the delivery of innovative, cost-effective medicines to the worldwide hospital marketplace. The Company markets Angiomax(R) (bivalirudin) in the United States and other countries for use in patients undergoing coronary angioplasty, a procedure to clear restricted blood flow in arteries around the heart. The Company also has two products in late-stage development, Cleviprex(TM) (clevidipine butyrate) injectable emulsion and cangrelor. The Company's website is www.themedicinescompany.com.
Statements contained in this press release about The Medicines Company that are not purely historical, and all other statements that are not purely historical, may be deemed to be forward-looking statements for purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words "believes," "anticipates" and "expects" and similar expressions are intended to identify forward-looking statements. These forward-looking statements involve known and unknown risks and uncertainties that may cause the Company's actual results, levels of activity, performance or achievements to be materially different from those expressed or implied by these forward-looking statements. Important factors that may cause or contribute to such differences include whether the Company's products will advance in the clinical trials process on a timely basis or at all, whether clinical trial results will warrant submission of applications for regulatory approval, whether the Company will be able to obtain regulatory approvals, whether physicians, patients and other key decision-makers will accept clinical trial results, and such other factors as are set forth in the risk factors detailed from time to time in the Company's periodic reports and registration statements filed with the Securities and Exchange Commission including, without limitation, the risk factors detailed in the Company's Quarterly Report on Form 10-Q filed on May 12, 2008, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.
(1) Stone G, Witzenbichler B, Guagliumi, G, Peruga J, Brodie B, Dudek, D, Kornowski R, Hartman F, Gersh B, Pocock S, Dangas G, Wong S, Kirtane A, Parise H, Mehran R: HORIZONS-AMI Trial Investigators. Comparison of Bivalirudin to Heparin Plus Glycoprotein IIb/IIIa Inhibitors During Percutaneous Coronary Intervention in Acute Myocardial Infarction. N Engl J Med. 2008 May 22.
(2) Lincoff AM, Kleiman NS, Kereiakes DJ, Feit F, Bittl JA, Jackman JD, Sarembock IJ, Cohen DJ, Spriggs D, Ebrahimi R, Keren G, Carr J, Cohen EA, Betriu A, Desmet W, Rutsch W, Wilcox RG, de Feyter PJ, Vahanian A, Topol EJ; REPLACE-2 Investigators. Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial. JAMA. 2004 Aug 11;292(6):696-703.
(3) Stone GW, McLaurin BT, Cox DA, Bertrand ME, Lincoff AM, Moses JW, White HD, Pocock SJ, Ware JH, Feit F, Colombo A, Aylward PE, Cequier AR, Darius H, Desmet W, Ebrahimi R, Hamon M, Rasmussen LH, Rupprecht HJ, Hoekstra J, Mehran R, Ohman EM; ACUITY Investigators. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006 Nov 23;355(21):2203-16.
(4) Ndrepepa G, Berger P, Mehilli J, et al. Periprocedural Bleeding and 1 Year Outcome After Percutaneous Coronary Interventions: Appropriateness of Including Bleeding as a Component of a Quadruple End Point. JACC. 2008;51:690-697.
(5) American Heath Association. Statistics on Acute Coronary Syndrome, Heart Attack and Percutaneous Coronary Intervention. Available at: http://www.americanheart.org/downloadable/heart/1189623702347Stat%20on %20acute%20coronary%20syndromeFINAL.doc. (Due to its length, this URL may need to be copied/pasted into your Internet browser's address field. Remove the extra space if one exists.) Accessed September 27, 2007.
(6) Stone, G., et al. Bivalirudin for Patients with Acute Coronary Syndromes, N Engl J Med 2006; 355;21
Posted: May 2008