The Medicines Company Announces Investigational Lipid Modulating Agent, MDCO-216, Phase 1 Data Published in European Heart Journal- Cardiovascular Pharmacotherapy
The Medicines Company (NASDAQ:MDCO) today announced that the European Heart Journal – Cardiovascular Pharmacotherapy has published results of its Phase 1 study for MDCO-216, a compound under development for the reduction of atherosclerotic plaque burden and related life-threatening cardiovascular events in patients with coronary artery disease (CAD). MDCO-216 is a complex of dimeric recombinant apolipoprotein A-1 Milano (ApoA-1 Milano) and a phospholipid which was developed in an attempt to mimic pre-beta HDL and induce cholesterol efflux, the first step in reverse cholesterol transport, causing removal of cholesterol from the artery walls.
In a dose-dependent effect, a single infusion of MDCO-216 significantly increased ABCA1-mediated cholesterol efflux, a biological marker for the reverse transport of cholesterol away from the arterial walls and into the blood for subsequent clearance from the body.
“MDCO-216 is truly a novel compound with a fascinating origin that has shown exciting potential for reducing atherosclerotic plaque burden and the subsequent cardiovascular consequences of this well-established risk,” said Clive Meanwell, MD, PhD, Chief Executive Officer, The Medicines Company. “Publication in the European Heart Journal-Cardiovascular Pharmacotherapy validates the promise of this agent and further establishes its meaningful place in our versatile portfolio of existing and investigational therapies for serious cardiovascular diseases.”
In an accompanying editorial, Antonio J. Vallejo-Vaz and Kausik K. Ray, Department of Primary Care and Public Health, Imperial Centre for Cardiovascular Disease Prevention, School of Public Health, Imperial College London, state that “The results reported by Kallend et al. are preliminary but promising and should encourage further confirmation in larger randomized trials assessing the effects of MDCO-216 on atherosclerosis and cardiovascular outcomes. Its intravenous administration and the duration of the effects suggest that it might be more suitable for patients with acute or unstable cardiovascular disease (CVD) rather than giving repeated infusions over time in subjects who are otherwise stable.”
In related news, The Medicines Company also announced that it has recruited and dosed the first patient in a proof-of-concept (POC) intravascular ultrasound (IVUS) study, MILANO-PILOT, that will assess the safety and efficacy of MDCO-216. MILANO-PILOT is a double-blind, placebo-controlled trial that will use IVUS (Intravascular Ultrasound) to measure the effect of MDCO-216 on atherosclerotic plaque burden and continue to evaluate the agent’s impact on cholesterol efflux. The study will involve up to 120 patients with ACS and will assess the safety and efficacy of weekly 20mg/kg MDCO-216 infusions over a five-week period. The first interim analysis is projected for the first half of 2016.
MILANO-PILOT will be conducted at multiple sites in North America and Europe. The first site to enroll patients is the Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ) in Montreal, for which Health Canada and a local investigational review board (IRB) have allowed The Medicines Company to proceed with initiating the trial. Dr. Josep Rodés-Cabau, Director of the Cardiac Catheterization Laboratories at the IUCPQ, and colleagues successfully enrolled the first patient today.
“We are extremely excited here at the IUCPQ to play an important role in the development of this recombinant ApoA-1 Milano compound, which we know originally made headlines just over ten years ago when it was shown to induce rapid plaque regression in the coronary arteries of patients presenting with a heart attack, when measured with intravascular ultrasound. We will continue to enroll more patients and very much look forward to the results of this initial pilot study, as well as the ongoing clinical development of this compound,” said Dr. Rodés-Cabau.
MDCO-216 Phase I Results
The Phase 1 study involved 24 healthy volunteers and an equal number of patients with documented CAD. Participants received a single, two-hour infusion of MDCO-216 in doses ranging from 5-40 mg. under a randomized, placebo-controlled protocol. All were followed for 30 days.
Investigators observed in both groups dose-dependent increases in ApoA-I, POPC and prebeta-1 HDL as well as decreases in Apo E, a protein instrumental to arterial plaque accumulation. Although the pharmacokinetic activity of the compound was the same in both groups, the most pronounced effects on cholesterol efflux were seen in CAD patients at doses of 20 mg and above.
MDCO-216 was well tolerated by all subjects. The most common adverse events were headache and fatigue occurring in equally low percentages in both groups.
Topline findings of the Phase 1 trial were originally presented in November 2014 at the AHA Scientific Sessions 2014 in Chicago, USA.
MILANO PILOT Trial Design
MILANO-PILOT is a double-blind, placebo controlled trial that will use IVUS (Intravascular Ultrasound) to measure the effect of MDCO-216 on atherosclerotic plaque burden and continue to evaluate the agent’s impact on cholesterol efflux. The study will involve up to 120 patients with ACS and will likewise assess the safety of weekly 20mg/kg MDCO-216 infusions over a five-week period.
Additional Canadian sites will begin enrolling patients shortly once they have received IRB approvals. Sites in The Netherlands, Poland, Hungary, Czech Republic and the U.S. plan to begin recruitment by the end of this year or early next year.
MDCO-216, an investigational product not approved for commercial use in any market, is a complex of dimeric recombinant apolipoprotein A-1 Milano (ApoA-1 Milano) and a phospholipid (POPC) and is currently under development to improve cardiovascular outcomes by reducing plaque burden in patients with atherosclerotic disease. MDCO-216 mimics pre-beta HDL and induces cholesterol efflux, which is the first step in the reverse cholesterol transport, a process of removal of deposited cholesterol from vessel walls and therefore has a potential to reduce plaque burden in patients with CAD. ApoA-1 Milano is a protein discovered in residents of a Northern Italian village who remarkably have little atherosclerotic build-up despite exceptionally low levels of cardioprotective HDL in combination with elevated levels of harmful triglycerides.
About The Medicines Company
The Medicines Company's purpose is to save lives, alleviate suffering and contribute to the economics of healthcare by focusing on 3000 leading acute/intensive care hospitals worldwide. Its vision is to be a leading provider of solutions in three areas: serious infectious disease care, acute cardiovascular care and surgery and perioperative care. The company operates in the Americas, Europe and the Middle East, and Asia Pacific regions with global centers today in Parsippany, NJ, USA and Zurich, Switzerland.
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," “projected,” "anticipates," "expects," “hopes” and “potential” 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 physicians, patients and other key decision makers will accept clinical trial results; the Company’s ability to successfully compete with potential competitors which may discover, develop or commercialize competing products more successfully than we do; whether third parties on whom the Company relies to manufacture and support the development and commercialization of MDCO-216 are able to fulfill their obligations or the Company is able to establish or maintain such arrangements; 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 with the SEC on November 9, 2015, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.
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