The Medicines Company Resumes Clevidipine Phase III Program; Phase III Interim Data Review Affirms Safety Profile

The Medicines Company (NASDAQ: MDCO) today announced that it is resuming Phase III clinical safety trials of clevidipine – its intravenous, short-acting antihypertensive agent. Review of interim safety results showed no significant differences between clevidipine and comparator treatments. Specifically, the incidence of atrial fibrillation was found to be similar between the randomized groups and in line with published data from other studies. The Company anticipates completing enrollment in the clinical safety studies in the next 12 months. Pivotal clinical efficacy studies were completed successfully in 2004, and met their pre-specified protocol objectives.

The Company announced in March a voluntary suspension of patient enrollment in the Phase III safety trials because preliminary data from an interim analysis contained more frequent reports of atrial fibrillation in patients randomized to clevidipine than in patients randomized to comparator drugs. These preliminary data from 750 patients, available at that time, showed atrial fibrillation rates of 25% on clevidipine and 15% on comparator agents. Both rates were well within the ranges reported in the cardiac surgery literature.

The completed interim data review included 880 patients and a more detailed assessment of atrial fibrillation risk factors, incidence, treatment and outcomes. The completed data show atrial fibrillation rates of 34% and 31% in clevidipine and comparator groups respectively, with no differences in duration, severity, treatments or outcomes reported. Other safety measures in the trial were also satisfactory.

The completed data for the interim analysis have been reviewed by the independent Drug Safety Monitoring Board of the trials, who supported the resumption of patient enrollment. The Company has reported the interim results and the restart decision to the U.S. Food and Drug Administration (FDA).

Professor Jerrold Levy, M.D., a clevidipine clinical investigator and Director of Cardiothoracic Anesthesiology and Critical Care at Emory Healthcare Atlanta, GA said, “This is a satisfactory outcome to an example of careful safety monitoring and trial management. The more detailed data collection shows atrial fibrillation rates consistent with published data and no evidence that clevidipine confers any additional risk over and above cardiac surgery itself. In addition, the data is consistent with the safety profile of intravenous dihydropyridines in this setting. It’s good to see clevidipine back in the clinic, because it is clearly effective and can become an important new agent in the management of hypertension in cardiac surgery and other acute care settings.”

Mark Sumeray, M.D., Vice President of Clinical Development at The Medicines Company said, “We anticipate restarting sites immediately, facilitating institutional review board approvals, sending out new drug supply and initiating patient enrollment from January onwards. We expect to proceed to an NDA filing as soon as the trials are completed.”

Clevidipine is an intravenous L-calcium channel blocker, a dihydropyridine, a widely used class of antihypertensives. In previous clinical trials, clevidipine has demonstrated arterial selectivity, a very short plasma half-life allowing for dose titration and elimination independent of renal or hepatic function. If the safety of clevidipine is confirmed in Phase III trials, this combination of attributes may position clevidipine as a unique agent for the treatment of hypertension associated with cardiac surgery – the most frequent occurrence of severe acute hypertension.

According to hospital discharge data, each year in the U.S., approximately 2.9 million hospitalized patients experience severe acute hypertensive episodes and receive an intravenous antihypertensive.

The clevidipine Phase III program is comprised of five clinical trials. The efficacy trials are called ESCAPE and the safety trials are called ECLIPSE.

Results of completed ESCAPE efficacy trials demonstrated clevidipine reduced high blood pressure in cardiac surgery patients. In two randomized trials the pre-specified primary endpoint of a 15% reduction in blood pressure was shown in more than 90% of patients given clevidipine compared to about 20% given placebo (p-value less than 0.00001).

The resumed ECLIPSE safety trials are evaluating clevidipine perioperatively in approximately 1,500 patients. The primary objective of ECLIPSE is to establish the safety of clevidipine for the management of perioperative hypertension, as measured by a comparison of the incidences of death, stroke, myocardial infarction and renal dysfunction between the clevidipine and comparative treatment groups. The comparative treatments are nitroglycerin, sodium nitroprusside and nicardipine.

The Medicines Company (NASDAQ: MDCO) 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 anti-clotting therapy approved in the U.S. and other countries for use in patients undergoing coronary angioplasty, a procedure to clear restricted blood flow in arteries around the heart. The Medicines Company creates value using its range of clinical and commercial skills to develop products acquired from leading life science innovators. The Company’s website is http://www.themedicinescompany.com.

Statements contained in this press release about the Company and its product clevidipine, including clinical development of clevidipine, 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 uncertainty of the results of our trials, the rate of enrollment in the ECLIPSE trial program, timely completion of the ECLIPSE trials, whether final data from the ECLIPSE trials are consistent with interim data, whether the FDA will interpret trial data in the same manner as the Company, whether clevidipine will advance in the clinical trials process, whether results from our clevidipine trial program warrant the submission of an NDA, the clevidipine will receive approvals from regulatory agencies 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 August 8, 2005, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.