Date: 2014-11-16
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at 2014 AHA Annual Scientific Sessions Meeting in Chicago
Company: The Medicines Company (USA - NJ)
Product: MDCO-216
Action
mechanism: MDCO-216 is a complex of recombinant ApoA-I Milano and phospholipid (POPC) manufactured by a new process to resemble a pre-beta-like high-density lipoprotein (HDL) particle. It has the potential to modify atherosclerotic disease by promoting reverse cholesterol transport and may, in the future, be tested in trials to measure reductions in the risk of adverse atherothrombotic events.
Disease: coronary artery disease
Therapeutic area: Cardiovascular diseases
Country:
Trial details:
Latest
news: * On November 16, 2014, The Medicines Company presented findings from a new Phase 1 study showing that a single infusion of MDCO-216, an investigational lipid-modifying agent, in both healthy and CAD patients, modified key lipid parameters including ApoA-1, phospholipids, HDL, pre-beta 1 HDL and Apo E, markedly increased ABCA1 mediated efflux, a potential marker of reverse cholesterol transport and was well tolerated. The study was presented as part of a poster session at The American Heart Association’s Annual Scientific Sessions in Chicago. Clinical findings have shown that human carriers of the ApoA-1 Milano variant have a reduced incidence of cardiovascular disease. MDCO-216, currently under development by The Medicines Company, is a complex of recombinant human Apo A1 with phospholipids to emulate an HDL particle. MDCO-216 has the potential to modify atherosclerotic disease by promoting reverse cholesterol transport, and its potential impact on reducing cardiovascular events in acute coronary syndrome (ACS) patients. In the Phase 1 study, 24 healthy volunteers and 24 patients with documented CAD received a 2-hour infusion of MDCO-216 in a randomized, placebo-controlled, single ascending dose study. Five cohorts of healthy volunteers and four cohorts of CAD patients received doses ranging from 5 - 40 mg/kg. Subjects were followed for 30 days and returned throughout the study for safety assessments. In both healthy volunteers and stable CAD patients, dose dependent increases in ApoA-1, phospholipid and prebeta-1 HDL and decreases in Apo E were observed. Prominent and sustained increases in triglyceride and decreases in HDL-C occurred at doses above 20 mg/kg in both healthy volunteers and patients with CAD. In both subject populations, profound increases in ABCA1 mediated cholesterol efflux were observed. Other lipid and lipoprotein parameters were generally unchanged with increases in HDL particle size and a shift to larger HDL particles. The study also demonstrated that MDCO-216 was well tolerated with no serious adverse events and no other significant adverse safety findings, including laboratory parameters. The Medicines Company expects to initiate a Phase 2 trial of MDCO-216 in 2015.
