Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company based in Cambridge, Massachusetts, announced positive top-line results from the company's randomized, double-blinded, placebo-controlled phase II clinical trial of MLN1202, a novel humanized monoclonal antibody that specifically targets the CCR2 chemokine receptor, in patients at high risk for atherosclerotic cardiovascular disease.
Preliminary analysis showed that MLN1202 was well tolerated and fully met its primary endpoint of a significant reduction in C-Reactive Protein (CRP) levels, an inflammatory biomarker associated with atherosclerosis, for months after a single dose of MLN1202. These results were statistically and clinically significant relative to the placebo control arm (p = 0.0275). No serious adverse events were observed in patients exposed to MLN1202. Trial results are expected to be submitted for presentation at a medical meeting.
"The sustained activity of MLN1202 on CRP as seen in this trial of patients at high-risk for atherosclerosis offers potential for anti-inflammatory activity in the treatment of coronary artery disease," said Eugene Braunwald, M.D., M.A.C.C., Chairman, TIMI Study Group, Brigham and Women's Hospital. "Well-documented clinical studies suggest that successful prevention and treatment of coronary atherosclerosis supports monitoring of inflammation as well as cholesterol. These studies further suggest that statins alone may not be sufficient in the treatment of all patients. CRP is a well-established inflammatory prognostic indicator for cardiovascular events, and the effect that MLN1202 has on reducing CRP may be clinically meaningful."
The phase II clinical trial enrolled 108 patients who were at high risk for atherosclerosis and had documented elevations in CRP. Patients were randomized to receive a single dose of either MLN1202 or placebo and were then evaluated over a period of months for tolerability and CRP levels.
CRP is a critically important biomarker of cardiovascular risks. An increase in levels of this protein is a prognostic indicator for poor outcomes, including death, as documented in key medical literature over the past few years. Recent landmark clinical studies have shown that reduction in CRP levels are associated with reduced coronary atherosclerosis, as measured by imaging of plaque, and with a reduced risk of cardiovascular events. Using biomarkers, such as CRP, to better understand key pathways involved in certain diseases is a critical component of all Research and Development programs at Millennium.
"We are extremely encouraged by these data and believe they are the first public data on CCR2 antagonism to show significant and sustained clinical activity," said Nancy Simonian, M.D., Senior Vice President, Clinical, Regulatory and Medical Affairs. "These data support our belief in the anti-inflammatory role of CCR2 and provide solid rationale for continued development of MLN1202 in atherosclerosis and other inflammatory diseases."
Millennium is also currently evaluating MLN1202 in a multicentre phase II clinical trial involving approximately 40 patients with relapsing-remitting multiple sclerosis. Data from this trial are expected in the first half of 2007. Additional studies of MLN1202 in other indications are planned.
MLN1202, a novel humanized monoclonal antibody, specifically targets CCR2 chemokine receptors found on the surface of certain white blood cells including macrophages and monocytes. Preclinical studies suggest that CCR2 plays an important role in the trafficking of monocytes and macrophages to sites of inflammation. The recruitment of macrophages to the arterial wall is believed to be a critical step in the development of atherosclerosis.