Millennium Pharmaceuticals, Inc. has announced that MLN1202, a novel, humanized monoclonal antibody met its primary endpoint of reducing C-reactive protein (CRP) levels in a placebo-controlled, Phase II trial of patients at high-risk for atherosclerotic cardiovascular disease.
CRP level is an important, independent marker of cardiovascular morbidity and mortality. Additionally, the Company announced the identification of a genomic biomarker, which may be used for selecting patients most likely to respond to MLN1202.
In this study, the genomic biomarker was identified in 53 percent of the overall patient population. These data were selected for oral presentation at the American Heart Association Scientific Session being held November 4-7, 2007 in Orlando, Florida.
"The anti-inflammatory effect of MLN1202 resulting in lower CRP, represents an exciting novel approach to reducing atherosclerosis by targeting inflammation," said Michael Davidson, M.D., Clinical Professor, Director of Preventive Cardiology, The University of Chicago Pritzker School of Medicine and Executive Medical Director, Radiant Research.
The Phase II clinical trial enrolled 108 patients at high-risk for atherosclerosis and with an elevated high-sensitivity CRP > 3.0 mg/dL. Patients were randomized to receive a single dose of either MLN1202 or placebo and were then followed for approximately 16 weeks.
Major findings of the trial include:
• A single dose of MLN1202 led to a median reduction in CRP of 26.7% relative to placebo on Day 57 after dosing (p = 0.0089), and was significantly reduced up to Day 85 (19.1%; p = 0.0203).
• 11.3% of MLN1202-treated patients experienced a reduction of CRP level to less than or equal to 2 mg/L compared to 1.9% for placebo patients at Day 57 (p = 0.0301).
• CRP reductions were more likely in patients with a specified genomic biomarker, a single nucleotide polymorphism (SNP) of a gene important in inflammatory pathways. The SNP was identified in 53 percent of the overall study population.
• In SNP-positive patients, a single dose of MLN1202 led to a median reduction in CRP of 35.3% relative to placebo at Day 57 (p =.0085).
• Among the MLN1202-treated patients, 15.4% of SNP-positive patients experienced a reduction of CRP level to less than or equal too 2 mg/L compared to 4.2% for SNP-negative patients at Day 57.
• MLN1202 lowered CRP levels similarly in subjects on lipid-lowering agents, such as statins, compared to those not on these agents.
• MLN1202 was well-tolerated with no evidence of systemic immunosuppression.
"These data support our belief in the anti-inflammatory role of a CCR2 antagonist and provide solid rationale for continued development of MLN1202 in atherosclerosis and other inflammatory diseases," said Nancy Simonian, M.D., Chief Medical Officer, Millennium.
"The association of a genomic biomarker with the biologic activity of the investigational drug validates our approach of using biomarkers to tailor drug treatments. We are actively seeking a partner to maximize the potential of MLN1202 in atherosclerosis and more broadly in other inflammatory diseases," she said.