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The Medicines Company, Inc.

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PLEASE SCROLL DOWN TO THE RESULTS SECTION (below) TO SEE THE OUTCOME OF THIS EVENT.

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Clive A. Meanwell, Chairman and CEO, gave guidance for data from the phase-I/II MILANO-PILOT study. He stated, "Similar to Dr. Nissen's original study, MILANO-PILOT is a double-blind placebo-controlled trial. The primary outcome measure is changed from baseline in percent atheroma volume from baseline to day 36. The trial is set-up to enroll up to 120 valuable patients. Two interim analysis are planned which allow early termination of the study when certain parameters for plaque regression are seen. Our goal is to complete enrollments and analysis of the first 40 patients by mid-2016. The trial is being conducted at 35 sites in Canada, Poland, Hungary, the Czech Republic, the Netherlands, and the United States. Further details of the trial are posted on ClinicalTrials.gov."
Source: Q4 2015 earnings conference call, 2/17/16.

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The Medicines Company Presents New Data Showing Remodeling Effect of MDCO-216 on HDL Particles in Coronary Artery Disease Patients

26 May 2015
PARSIPPANY, N.J.--(BUSINESS WIRE)--May 26, 2015-- The Medicines Company (NASDAQ:MDCO) presented the results of a Phase 1 study for MDCO-216 that showed that the drug had a significant remodeling effect on HDL particles, which correlated with increased ABCA1-mediated cholesterol efflux. This mechanism of HDL remodeling and increased cholesterol efflux may drive the removal of deposited cholesterol from vessel walls to reduce plaque burden in patients with atherosclerotic disease. The findings were presented at the 17th International Symposium on Atherosclerosis, May 23-26, in Amsterdam, The Netherlands.

MDCO-216 is a complex of dimeric recombinant apolipoprotein A-1 Milano (ApoA-1 Milano) and a phospholipid (POPC) 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.

A single infusion of MDCO-216 was shown to produce a rapid increase in ABCA1 mediated efflux, a potential marker of reverse cholesterol transport, and a marked increase in pre-beta 1 HDL. This was followed by and correlated with a decrease in smaller HDL particles and an increase in larger HDL particles which suggests significant and rapid HDL remodeling. This data provides a hypothesis for the mechanism by which MDCO-216 as a single infusion may increase the physiological process of reverse cholesterol transport and potentially reduce atherosclerotic plaque burden.

“This new data suggests that MDCO-216 may have a profound impact on the body’s ability to remove cholesterol from arterial walls,” said Clive Meanwell, MD, PhD, Chairman and CEO, The Medicines Company. “We continue to be excited about the potential of MDCO-216 to rapidly reverse atherosclerotic plaque buildup, Together with our first-in-class PCSK9 inhibitor, ALN-PCSsc, which has the potential to become the best-in-class therapeutic for the reduction of LDL cholesterol, we look forward to advancing these important compounds through clinical development.”

In other presentations at the conference of the Phase 1 data for MDCO-216,, investigators compared the pharmacokinetics and pharmacodynamics of MDCO-216 in healthy volunteers (HV’s) and CAD patients. MDCO-216 was found to profoundly stimulate the first step of reverse cholesterol transport at clinically achievable and well tolerated doses with similar PK profiles in both HV’s and coronary artery disease (CAD) patients, but with higher potency in terms of ABCA1 efflux in CAD patients.

In a separate presentation, investigators assessed the safety of newly manufactured MDCO-216 in HV’s and CAD patients. MDCO-216 was shown to be well tolerated with no serious events and no significant adverse safety findings. The most common adverse events were headache and fatigue. No dose dependent effect on any safety parameter was noted, including inflammatory markers, and there were no differences in safety parameters between HV’s and CAD patients.
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Source: press release, 5/26/15. http://www.themedicinescompany.com/investors/news/medicines-company-pres...

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MILANO-PILOT - A Placebo-controlled, Double-blind, Randomized Trial to Compare the Effect of Treatment on Plaque Burden as Determined by Intravascular Ultrasound and to Evaluate the Efficacy, Pharmacokinetics, Safety, and Tolerability of MDCO-216 Given as Multiple Weekly Infusions in Subjects With a Recent Acute Coronary Syndrome
Estimated Enrollment: 120
Study Start Date: December 2015
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
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Source: clinical trials.gov. https://clinicaltrials.gov/ct2/show/NCT02678923?term=MDCO-216&rank=1

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Compound/DeviceSpecialtyIndicationCompound ClassTarget
MDCO-216CardiovascularAtherosclerosisApolipoprotein A-1 Milano MimeticCholesterol

Mechanism of action: MDCO-216 is a ynthetic variant of high-density lipoprotein (HDL). HDL transports excess cholesterol and other lipids to the liver for elimination from the body. By removing excess cholesterol from the circulation, HDL can prevent arteries from becoming clogged with fatty material.

Phase of Development: I/II

Event Type: Data: Phase I/II trial results

Dates: 2016-10-01 - 2016-12-31

Results:

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The Medicines Company Discontinues Development of MDCO-216, its Investigational Cholesterol Efflux Promoter

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7 Nov 2016
— Top-line efficacy data from the MILANO-PILOT trial, which enrolled 126 patients, provide insufficient basis for further investment by the Company —

— Discontinuation will enable the Company to reallocate and focus substantial additional capital onto the development of its PCSK9 synthesis inhibitor —

— Results from the MILANO-PILOT trial will be presented in the Late-Breaking Clinical Trial Session at American Heart Association Scientific Sessions 2016 —

PARSIPPANY, N.J.--(BUSINESS WIRE)--Nov. 7, 2016-- The Medicines Company (NASDAQ:MDCO) announced today the immediate discontinuation of the clinical development program for MDCO-216, its investigational cholesterol efflux promoter. Data from the recently-completed MILANO-PILOT trial did not show drug effects on intracoronary atherosclerotic plaque sufficient to warrant further development. The safety profile of MDCO-216 was excellent.

Information now available to the Company from the MILANO-PILOT trial of MDCO-216, when evaluated in light of the evolving treatment landscape for atherosclerotic cardiovascular disease, including the emergence of highly-positive data from the ORION-1 trial of the Company’s PSCK9 synthesis inhibitor, drove the Company’s decision to discontinue further investment in the clinical development of MDCO-216. The Company’s decisive move will free up substantial additional capital, which will be reallocated and focused onto the development of its PCSK9 synthesis inhibitor, which demonstrated significant and durable LDL-C reduction in the ORION-1 trial — reaffirming a triannual, and potentially biannual, dosing regimen with high standards of safety and tolerability and a highly-competitive profile. Results from the ORION-1 trial, including Day 90 follow-up for all 501 patients, as well as top-line data from a preliminary analysis of Day 180 follow-up for up to 200 patients, will be presented in the Late-Breaking Clinical Trial Session at the AHA Scientific Sessions 2016, on November 15, 2016, in New Orleans.

“We deliberately focused our initial development investment in MDCO-216 on clinical proof of concept. Unfortunately, the efficacy data from MILANO-PILOT do not support a prudent decision to make the significant, near-term investment required to move MDCO-216 forward,” stated Clive Meanwell, M.D., Ph. D., Chief Executive Officer of The Medicines Company. “In spite of promising earlier research findings, and impressive progress with manufacturing development and safety, in the light of these efficacy data and in view of the potentially enormous opportunity and highly-favorable risk-reward profile presented by our PSCK9 synthesis inhibitor, we have been decisive in immediately terminating the MDCO-216 development program. This decision will allow us to reallocate substantial additional capital to the further development of our PCSK9 synthesis inhibitor. We are extremely grateful for the leadership of our lead investigators, Dr. Stephen J. Nicholls, MBBS, Ph.D., FRACP South Australian Health and Medical Research Institute, Adelaide, Australia, and Dr. Steven E. Nissen, M.D., Chairman of Cardiovascular Medicine, Cleveland Clinic, who continue to blaze a trail in the field with sophisticated and groundbreaking coronary ultrasound imaging studies. We have ensured that Drs. Nicholls and Nissen have full access to all data from MILANO-PILOT for analysis, presentation and publication. We also thank the patients and collaborators who participated in the MILANO-PILOT trial.”

The Company is supporting the close-out of the MILANO-PILOT trial and results will be presented by Dr. Nicholls, its principal investigator, in the Late-Breaking Clinical Trial Session at the American Heart Association (AHA) Scientific Sessions 2016, on November 15, 2016, in New Orleans.

The Company is working to ensure that all MILANO-PILOT trial investigators, regulatory authorities and collaboration partners are informed of the decision to discontinue further development of MDCO-216.

The Company does not expect to incur any charge associated with the discontinuation of the MDCO-216 development program.
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Source: press release, 11/07/16. http://www.themedicinescompany.com/investors/news/medicines-company-disc...

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