Healthcare Industry News: bivalirudin
News Release - October 23, 2007
Cleviprex(TM) (Clevidipine Butyrate) Rapidly Reduced Blood Pressure and Maintained Control in Study of Patients with Acute HypertensionCHICAGO--(HSMN NewsFeed)--The investigational antihypertensive drug Cleviprex™ (clevidipine butyrate injectable emulsion) rapidly reduced blood pressure and maintained blood pressure control in patients presenting to the emergency department with acute hypertension, according to data from the Phase III trial VELOCITY* presented today at the annual meeting of the American College of Chest Physicians (CHEST).1
Among patients treated in the trial with Cleviprex, which is administered by intravenous (IV) infusion, target blood pressure levels were reached by a median of 10.9 minutes, with 89% (104 of 117) of patients achieving their target within 30 minutes. Following initial blood pressure control, Cleviprex was infused continuously for a median of 21 hours to maintain blood pressure within target limits. Among patients who received 18 hours of continuous Cleviprex therapy, 92% (108 of 117) did not require the addition of other IV antihypertensive agents during the 18-hour period.
“The rapid control achieved with Cleviprex in this study is an important finding because every minute counts when treating acute hypertension. Maintaining target blood pressure can prevent potentially irreversible damage to the brain, heart, kidneys or blood vessels,” said presenter Joseph Varon, MD, Clinical Professor of Medicine, The University of Texas Health Science Center and St. Luke's Episcopal Hospital, Houston. “And our finding that continuous infusion of Cleviprex for a median of 21 hours maintained the target blood pressure is also important, because some patients require prolonged treatment with an IV agent to keep their blood pressure under control.”
Dr. Varon added that the findings with Cleviprex were also significant given the poor health status of patients in the study. Most (81%) had evidence of end-organ injury, including kidney disease (often requiring dialysis), coronary artery disease, and/or myocardial infarction. In addition, 97% had chronic hypertension, 31% had diabetes, 31% had been previously hospitalized for acute hypertension, and 18% had congestive heart failure.
Acute hypertension is commonly seen in the emergency department setting. Approximately 3 million patients are treated with IV antihypertensive agents each year in U.S. hospitals. One of the major risk factors for acute hypertension is having chronic high blood pressure, with affects an estimated 50 million Americans and 1 billion people worldwide.2 By the year 2025, an estimated one third of the world’s population will have hypertension. One to two people out of 100 with chronic hypertension have acute elevations of blood pressure that require urgent medical treatment.3
“Current agents for the treatment of acute hypertension have various shortcomings, and there have been no new therapies in 10 years,” said John Kelley, President and Chief Operating Officer of The Medicines Company. “There is a clear need for new and better IV antihypertensive agents that provide rapid, predictable and sustained blood pressure control, and we believe Cleviprex can meet that need.”
Studies and Findings
VELOCITY was an open-label, single-arm, multi-center study in 126 emergency department patients presenting with acute hypertension (average baseline systolic blood pressure [SBP] was 203 mmHg). For each patient, investigators determined a target SBP range to be achieved within the first 30 minutes of clevidipine butyrate infusion. Investigators administered clevidipine butyrate using a non-weight-based dosing regimen and maintained or further titrated clevidipine butyrate therapy to achieve the desired long-term SBP target based on the needs of the individual patient. Oral antihypertensive therapy was begun one hour before anticipated cessation of clevidipine butyrate.
The onset of effect with clevidipine butyrate was rapid. Three minutes after administration, SBP decreased by 6% (12 mmHg) compared to baseline, and by 15% after a median time of 9.5 minutes. At 18 hours, SBP decreased by 27% (55 mmHg) compared to baseline. Each patient’s target SBP was maintained with minimal changes to the dose rate of clevidipine butyrate infusion throughout the treatment period.
The new VELOCITY findings are consistent with data reported last week at the American College of Clinical Pharmacy from a study evaluating the pharmacologic and safety profile of a prolonged infusion of clevidipine butyrate in 60 adult patients with essential hypertension.4 Eight to 14 days after the patients withdrew from their current antihypertensive medications, they were randomly assigned to receive IV placebo or one of four doses of IV clevidipine butyrate (2.0, 4.0, 8.0 or 16.0 mg/hour) for 72 hours. Patients treated with clevidipine butyrate maintained the reduced SBP at a constant level for the 72 hours and did not develop tolerance to the drug. When clevidipine butyrate was withdrawn, SBP rapidly returned to baseline, with no rebound hypertension and no drug accumulation. There were no serious adverse events.
Other data from VELOCITY, reported last week at the American College of Emergency Physicians, showed that 97.5% of patients who received IV clevidipine butyrate and who were eligible to switch to oral therapy did so successfully – as defined by achieving their target SBP – within six hours of starting oral therapy.5
About Acute Hypertension
Acute hypertension is a rapid and severe increase in blood pressure that can damage blood vessels, resulting in inflammation and leakage of fluid or blood into surrounding tissues or irreversible organ damage in the central nervous system, heart, vasculature and kidneys. It is critical to safely reduce blood pressure within minutes to hours to avoid morbidity and mortality. Acute hypertension often occurs in people who have untreated or inadequately controlled chronic hypertension, and can occur in a broad range of patients.
Cleviprex is a novel investigational IV antihypertensive for the treatment of acute hypertension when the use of oral therapy is not feasible or desirable. Cleviprex has a rapid onset and offset of action and can be titrated for predictable blood pressure control. Unlike current antihypertensive treatments which are metabolized by the kidney or liver, Cleviprex is metabolized in the blood and does not accumulate in the body, making it suitable for patients with end-organ damage.
Cleviprex has been studied in more randomized clinical trials and in more patients than any other IV antihypertensive agent. Six Phase III trials of Cleviprex met all of their primary endpoints. The most common adverse reactions seen with Cleviprex use were headache, sinus tachycardia, hypotension, nausea, polyuria, flushing, dizziness and vomiting.
About The Medicines Company
The Medicines Company (NASDAQ: MDCO ) is committed to delivering innovative, cost-effective acute care products in the worldwide hospital marketplace. The Company markets Angiomax® / Angiox® (bivalirudin) 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 Company also has two products in late-stage development, CleviprexTM (clevidipine butyrate injectable emulsion) and cangrelor. The Company's website is http://www.themedicinescompany.com.
Statements contained in this press release about The Medicines Company and Cleviprex 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 August 9, 2007, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.
* EValuation of the Effect of ULtrashOrt-Acting Clevidipine In the Treatment of Patients With Severe HYpertension
1 Varon J, Peacock W, Garrison N, Ebrahimi R, Dunbar L, Acosta P, Pollack C. Prolonged Infusion of Clevidipine Results in Safe and Predictable Blood Pressure Control in Patients with Acute Severe Hypertension. Poster presentation at: annual meeting of the American College of Chest Physicians (CHEST); 2007 Oct 20-25; Chicago.
2 Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003 May 21; 289(19):2560-72. 2003 May 14.
3 Marik PE, Varon J: Hypertensive crises: challenges and management. Chest. 2007 Jun; 131(6):1949-62.
4 Smith WB, Marbury TC, Komjathy SF, Sumeray M. The pharmacokinetics and pharmacodynamics of clevidipine after prolonged continuous infusion in patients with essential hypertension. Poster presentation at: American College of Clinical Pharmacy 2007 Annual Meeting; 2007 Oct 14-17; Denver, Colorado.
5 Peacock WF, Varon J, Garrison N, Ebrahimi R, Dunbar L, Pollack Jr. CV. IV Clevidipine for hypertension: safety, efficacy, and transition to oral therapy. Poster presentation at: 38th annual Scientific Assembly of the American College of Emergency Physicians; 2007 Oct 8-11; Seattle.
Source: The Medicines Company
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