Biotech Values

[DewDiligence]

Here’s the abstract of the new M118 paper in Circulation.
The content is similar to the Nov 2009 paper in the Journal
of Thrombosis and Hemostasis (#msg-43301340). Please see
#msg-41846746 for the detailed results from the EMINENCE
study, and see #msg-39146357 for a refresher course on the
rationale for the M118 program.

http://www.ncbi.nlm.nih.gov/pubmed/20368520

›Evaluation of a New Heparin Agent in Percutaneous Coronary Intervention. Results of the Phase 2 Evaluation of M118 IN pErcutaNeous Coronary intErvention (EMINENCE) Trial

Circulation. 2010 Apr 5. [Epub ahead of print]

Rao SV, Melloni C, Myles-Dimauro S, Broderick S, Kosinski AS, Kleiman NS, Dzavík V, Tanguay JF, Chandna H, Gammon R, Rivera E, Alexander JH, Fier I, Roach J [MNTA’s CMO], Becker RC.

Duke Clinical Research Institute, Durham, NC; Methodist DeBakey Heart Center, Houston, Tex; University Health Network, Toronto General Hospital, Toronto, Ontario, Canada; Montreal Heart Institute, Montreal, Quebec, Canada; Victoria Heart and Vascular Research, Victoria, Tex; Austin Heart, Austin, Tex; Northwest Texas Healthcare System, Amarillo, Tex; and Momenta Pharmaceuticals, Inc, Cambridge, Mass.

Background

Factor Xa and factor IIa (thrombin) play roles in thrombotic complications after percutaneous coronary intervention. M118 is a novel low-molecular-weight heparin that has been rationally designed to capture the desired attributes of unfractionated heparin (UFH) and low-molecular-weight heparin: Potent activity against factor Xa and IIa, predictable pharmacokinetics after both intravenous and subcutaneous administration, ability to be monitored by use of point-of-care coagulation assays, and reversibility with protamine sulfate. We performed a phase 2 randomized trial to evaluate the safety and feasibility of M118 in the setting of elective percutaneous coronary intervention.

Methods and Results

Overall, 503 patients undergoing elective percutaneous coronary intervention at 43 centers in the United States and Canada were randomized in an open-label fashion to 1 of 4 arms: UFH 70 U/kg, M118 50 IU/kg IV, M118 75 IU/kg IV, or M118 100 IU/kg IV. The primary outcome was the composite of death, myocardial infarction, repeat revascularization, stroke, thrombocytopenia, catheter thrombus, bailout use of glycoprotein IIb/IIIa inhibitor, or any bleeding through 30 days. The primary end point occurred in 31.1% of patients randomized to UFH and in 22.7%, 28.3%, and 30.1% of patients randomized to M118 50, 75, and 100 IU/kg, respectively. The primary analysis comparing the rates of the primary end points between the pooled M118 groups versus UFH demonstrated that M118 was noninferior to UFH at preventing percutaneous coronary intervention-related complications (28.4% pooled M118 arms versus 31.1% UFH). The adverse event profiles of M118 and UFH were comparable.

Conclusions

This phase 2 randomized trial demonstrates that M118 is well tolerated and feasible to use as an anticoagulant in patients undergoing elective percutaneous coronary intervention and forms the basis for further investigation of this agent in ischemic heart disease.‹