The Medicines Company Completes Angiomax -Bivalirudin- Phase III Safety Trials in Cardiac Surgery.

PARSIPPANY, N.J. -- EVOLUTION-On Trial Meets Primary Objective Comparing Angiomax Alone to Heparin with Protamine Reversal

The Medicines Company (Nasdaq: MDCO) today announced successful completion of the EVOLUTION-On Phase III clinical trial of Angiomax(R) (bivalirudin), the second of two safety trials of the Angiomax Phase III cardiac surgery program. EVOLUTION-On evaluated the use of Angiomax as an anticoagulant during cardiac surgeries conducted with the use of a cardiac pulmonary bypass machine ("on-pump").

The primary objective of EVOLUTION-On was to demonstrate that Angiomax is a safe alternative anticoagulant to heparin with protamine reversal in on-pump cardiac surgery. The primary endpoint results, a comparison of rates of acute procedural success, met the pre-specified objectives. Patients treated with Angiomax demonstrated a 95.0% success rate, compared to a 91.8% success rate in patients treated with heparin and protamine reversal. Acute procedural success was defined at seven days post-surgery as absence of death, Q-wave MI (heart attack), repeat operation or catheterization for coronary revascularization, or stroke.

Mark Sumeray, MD, Vice President of Product Development at The Medicines Company, stated, "With completion of EVOLUTION-On, The Medicines Company has finished the safety portion of the Phase III clinical trial program of Angiomax in cardiac surgery. If the Phase III efficacy studies known as CHOOSE meet their endpoints, we expect to file for U.S. regulatory clearance to use Angiomax in cardiac surgery patients with a condition known as HIT/TS. If approved for use in patients with HIT/TS for a surgery indication, Angiomax would be the first new anticoagulant introduced to the operating suite since the first cardiac surgeries were conducted in the 1950's."

Clive Meanwell, Chairman and CEO of The Medicines Company, noted, "We had ambitious clinical trial plans for 2004 at The Medicines Company, with ten Phase III clinical trials operating concurrently in three program areas -- Angiomax in the treatment of acute coronary syndromes, Angiomax in cardiac surgery, and Clevelox(TM) (clevidipine) in cardiac surgery. With completion of the second Phase III safety trial of Angiomax in cardiac surgery added to the recently announced completion of the two Phase III efficacy trials of Clevelox, we close out the year having reached important timeline goals to keep us on track for expected future growth."

Cardiac Surgery Background

Cardiac surgery, commonly referred to as "open heart surgery," is performed to treat ischemic heart disease or to repair parts of the heart, either on-pump or off-pump. On-pump cardiac surgery is conducted with the use of a cardiac pulmonary bypass machine, a device that pumps the patient's blood while the heart is stopped and the surgery is performed. For off-pump cardiac surgery, physicians slow the heartbeat, stabilize the heart by keeping certain areas immobile with various devices, and perform the surgery without the use of a bypass machine.

Anticoagulation of the patient's blood is necessary during the period of cardiopulmonary bypass in order to prevent clots forming in the machine or in the patient's cardiovascular system. Heparin has been the standard anticoagulant for cardiac surgery since the 1950's. Because heparin's duration of effect is variable and sometimes prolonged, surgeons usually give protamine to reverse heparin at the end of surgery. Both heparin and protamine can cause immune reactions, which may compromise patient survival and treatment results, and may also result in greater procedure costs.

About Angiomax Phase III Cardiac Surgery Program

The Medicines Company is sponsoring the Phase III clinical study program investigating Angiomax as an anticoagulant in both on-pump and off-pump cardiac surgery to address a medical need among patients with or at risk for heparin-induced thrombocytopenia and thrombosis syndrome (HIT/TS). HIT/TS occurs when a patient exposed to heparin forms heparin antibodies. If heparin is administered again to a patient while heparin antibodies are present, that patient is at a significantly higher risk of developing HIT/TS. HIT/TS results in reduced platelet counts (HIT) and may progress to widespread, life-threatening blood clots (HIT/TS). There is currently no approved alternative to heparin for patients undergoing cardiac surgery where heparin is contraindicated, such as patients with HIT/TS.

The efficacy portion of the Phase III program is comprised of the CHOOSE studies, in which Angiomax is being evaluated in patients with or at risk for HIT/TS who will be undergoing on-pump and off-pump cardiac surgery. In CHOOSE, HIT/TS is defined as a positive functional test for HIT antibodies, a platelet count decrease of 50% associated with heparin therapy, or the platelet count decrease plus any evidence of arterial or venous clotting.

The safety portion of the Phase III program is the EVOLUTION studies, which were conducted in the general cardiac surgery patient population. Primary results of EVOLUTION-Off, a 150-patient study in patients undergoing off-pump cardiac surgery, announced by The Medicines Company on November 11, 2004, met the pre-specified primary endpoint objectives.

Both the EVOLUTION-On and EVOLUTION-Off trials were open-label, multi-center, randomized studies. The Medicines Company expects full data results from the EVOLUTION program to be published and/or presented under scientific peer review.

About Angiomax

Angiomax(R) (bivalirudin) is currently approved in the U.S. and the European Union, as well as other countries. Angiomax is a direct thrombin inhibitor with a naturally reversible mechanism of action. In clinical trials, Angiomax has demonstrated reductions in both ischemic and bleeding complications compared to heparin as the foundation anticoagulant in the contemporary catheterization lab setting. These reductions in ischemic and bleeding complications remain evident even in high-risk patients.

In the U.S., Angiomax is indicated for use as an anticoagulant in patients with unstable angina 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 U.S. prescribing information available at http://www.angiomax.com.

About The Medicines Company: The Medicines Company meets the demands of the world's most advanced medical practitioners by developing products that improve acute hospital care. The Company markets Angiomax(R) (bivalirudin), an anticoagulant approved in the U.S. and other countries for use in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) procedures. The Medicines Company creates value using its range of clinical and commercial skills to develop products acquired from leading life science innovators.

Statements contained in this press release about the Company, its products, and the Company's projected financial results 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," "plans," "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 the extent of the commercial success of Angiomax, the uncertainty of the results of our trials, whether the development and commercialization of our products may be terminated or delayed, whether the Company's products will advance in the clinical trials process, whether the Company's products will receive approvals from regulatory agencies, physicians' acceptance of clinical trial results, whether the Company will be able to acquire and develop additional product candidates, 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 November 5, 2004, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.