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Momenta Pharmaceuticals Announces Positive Results From M118 EMINENCE Trial

[Please see #msg-41820503 for background. The results clearly support the goal of the study, which is to advance M118 into phase-2b trials in ACS.]

http://finance.yahoo.com/news/Momenta-Pharmaceuticals-pz-4042311192.html?x=0&.v=1

›Data Supports Feasibility of Utilizing M118 as a Procedural Anticoagulant

Thursday September 24, 2009, 2:45 pm EDT

CAMBRIDGE, Mass., Sept. 24, 2009 (GLOBE NEWSWIRE) -- Momenta Pharmaceuticals, Inc. (Nasdaq: MNTA ), a biotechnology company specializing in the characterization and engineering of complex drugs, today announced the results from the EMINENCE (Evaluation of M118 in Percutaneous Coronary Intervention) Phase 2 multicenter trial evaluating intravenous use of M118. The results were presented at the 21st Annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation, being held in San Francisco, CA. Sunil V. Rao, M.D., co-principal investigator for the trial, presented the results as a "First Report" during a session on novel antithrombotic agents. Dr. Rao is an Assistant Professor of Medicine at the Duke University Medical Center and Director of the Cardiac Catheterization Laboratories at the Durham, NC Veterans Affairs Medical Center.

"M118, our first novel product engineered utilizing Momenta technology, was rationally designed to capture the positive attributes of both unfractionated heparin and low molecular weight heparin," commented Jim Roach, M.D., Chief Medical Officer at Momenta. "We are very pleased with the results from the EMINENCE trial, which support our belief that M118 has the potential to become the baseline anticoagulant of choice for treatment of patients diagnosed with acute coronary syndromes."

The primary objective of EMINENCE was to evaluate the safety and feasibility of utilizing M118 as an anticoagulant in the target population of patients with stable coronary artery disease (CAD) undergoing a percutaneous coronary intervention (PCI). Approximately 500 patients with stable CAD undergoing elective PCI were randomly assigned to receive treatment with one of three doses of intravenous M118 or a standard dose of unfractionated heparin (UFH).

The primary endpoint of the study was the combined incidence of clinical events defined as the composite of death, myocardial infarction (MI), repeat revascularization, and stroke (over thirty days); incidence of bleeding and thrombocytopenia (over the first 24 hours); and bailout use of glycoprotein IIb/IIIa inhibitors and catheter thrombus (during the procedure). Safety was also evaluated by assessing the incidence of adverse events and serious adverse events.

Key Results:

* The combined incidence rate of the primary endpoint was 31.1% for patients in the UFH arm vs. 28.4% of patients in the combined M118 arms [note: lower is better]. A patient was included in the calculation of incidence of the primary endpoint if that patient experienced at least one of the events included in the composite endpoint.

* The incidence rate of the primary endpoint excluding minor bleeding within 24 hours of PCI, a prespecified secondary endpoint, was 17.9% for patients in the UFH arm vs. 11.4% of patients in the 50 IU/kg M118 dosage arm, 12.5% of patients in the 75 IU/kg M118 dosage arm, and 14.1% of patients in the 100 IU/kg M118 dosage arm.

* The event rates for the prespecified composite secondary endpoint of death, MI, or repeat revascularization at 30 days -- a composite often used for pivotal registration trials -- were 11.4%, 7.9%, and 6.4% in the 50 IU/kg, 75 IU/kg, and 100 IU/kg M118 dosage arms, respectively, vs. 8.6% of patients in the UFH arm. For death or MI at 30 days, the incidence was 11.4%, 6.6%, and 5.8% in the 50 IU/kg, 75 IU/kg, and 100 IU/kg M118 dosage arms, respectively, vs. 6.0% of patients in the UFH arm.

* Bleeding, which was classified according to the REPLACE-2 scale, was comparable in all dose groups. Major bleeding occurred in 1.3% of patients who received UFH vs. 2.3%, 0.7% and 1.3% in the 50, 75 and 100-IU/kg M118 doses, respectively. Minor bleeds were reported in 15.9% of UFH patients and 11.4%, 17.1% and 19.9% for the 50, 75, and 100 IU/kg M118 doses, respectively.
-- A post-hoc analysis evaluating the rate of bleeding by the TIMI scale showed comparable rates of either major (0.7% vs. 0.3%) or minor (1.4% vs. 1.5%) bleeding for UFH and the combined M118 dose groups, respectively.

* Bailout GPI use was also less frequent in the M118 50, 75, and 100-IU/kg arms (4.5%, 2.0%, and 3.2% of patients, respectively) than in the UFH arm (8.1% of patients). In addition, none of the patients treated with M118 developed a catheter thrombus, compared with one patient in the UFH arm.

* The incidence of adverse events was comparable across all groups. Serious Adverse Events (SAEs) were reported in 13.2% of patients receiving UFH, and 15.9% 8.6% and 9.6% in the 50, 75, and 100-IU/kg M118 dose groups, respectively. The overall incidence of SAEs in the combined M118 group was 9.9%. The most common SAEs overall were investigator-identified MI (2.6%), angina pectoris (1.2%), noncardiac chest pain (1.2%), and unstable angina (0.8%).

Commenting on the results, Dr. Rao stated: "The EMINENCE trial met its goal of supporting the feasibility and tolerability of M118 use as a procedural anticoagulant in the coronary catheterization laboratory. Should the efficacy and safety observations from the Phase 2 program be demonstrated in larger Phase 3 trials, M118 may become an important treatment option given the limitations of currently available agents."

Ian Fier, Vice President, Development Operations at Momenta, and the M118 Program Leader, said: "We are encouraged by these results of the first use of M118 in patients with coronary artery disease undergoing an intervention, particularly the observation of a reduction in clinical events despite the relatively short-term administration of M118 in the catheterization lab. We believe these results support our plans to continue the evaluation of M118 in patients diagnosed with Acute Coronary Syndromes who are medically managed with or without an intervention."

About EMINENCE

The EMINENCE trial was designed to demonstrate the utility of M118 in patients with stable angina undergoing an elective PCI. Patients scheduled to undergo elective PCI, who met study eligibility criteria and for whom use of a glycoprotein IIb/IIIa inhibitor (GPI) was not intended, were randomly assigned to treatment with 1 of 3 doses (50 IU/kg, 75 IU/kg, or 100 IU/kg) of intravenous (IV) M118, or a standard unfractionated heparin (UFH) dose of 70 U/kg. Patients were also treated with at least 325 mg of aspirin and at least 300 mg of clopidogrel before PCI. The study was originally planned to include 150 patients in each arm, for a total of 600 patients. Enrollment into the lowest dose (50 IU/kg) was discontinued based on a recommendation by the Data Safety Monitoring Board [as previously reported], and consequently, approximately 500 patients in total were enrolled (44, 152, 156, patients enrolled in the 50 IU/kg, 75 IU/kg, and 100 IU/kg M118 arms respectively, and 151 patients in the 70 U/kg UFH arm).

The primary objective of EMINENCE was to evaluate the safety and feasibility of utilizing M118 as an anticoagulant in the target population of patients with stable CAD undergoing a PCI. A secondary objective was to evaluate the effect of M118 on procedural indices, including procedure success, abrupt closure, post-procedural Thrombosis in Myocardial Infarction (TIMI) flow grade, and catheter thrombus.

About M118

M118 is a novel anticoagulant that has been rationally engineered using Momenta's proprietary technology and analytical methods to provide anticoagulant therapy to patients with acute coronary syndrome (ACS). M118 is designed to interact at multiple points in the coagulation cascade by selectively binding to both anti-thrombin III and thrombin, two critical factors involved in the formation of clots. Preclinical and Phase 1 studies have shown that M118 is a potent inhibitor of multiple factors in the blood that lead to clot formation, that its anticoagulant effects can be neutralized and that its activity can be monitored with standard point-of-care assays. An anticoagulant possessing these properties has the potential to satisfy a currently unmet medical need within the ACS patient population by capturing, in a single anticoagulant therapy, the positive attributes of both UFH (reversibility, monitorability and broad inhibition of the coagulation cascade) and low molecular weight heparins (adequate bioavailability and predictable pharmacokinetics to allow for convenient subcutaneous administration). M118 is designed to be an anticoagulant that could potentially be used in multiple settings, including initial medical management of ACS, angioplasty, or coronary artery bypass surgery.

About Acute Coronary Syndromes

ACS is characteristically used to describe patients experiencing an acute myocardial infarction, or heart attack, as well as patients who present at hospitals with unstable angina, a transient blockage of a coronary artery. According to the National Hospital Discharge Survey, each year in the United States there are more than 1.5 million occurrences of either unstable angina or myocardial infarction requiring medical treatment. As part of the treatment of ACS, anticoagulant agents are routinely administered to prevent the accumulation and formation of blood clots which can lead to serious, life-threatening complications.

About Momenta

Momenta Pharmaceuticals is a biotechnology company headquartered in Cambridge, MA, specializing in the detailed structural analysis of complex mixture drugs. Momenta is applying its technology to the development of generic versions of complex drug products, as well as to the discovery and development of novel drugs. To receive additional information about Momenta, please visit the website at www.momentapharma.com, which does not form a part of this press release.‹