Millennium Pharmaceuticals, Inc. has announced the initiation of a randomized, double-blind, placebo-controlled phase II study of MLN3897 in patients with rheumatoid arthritis (RA).
MLN3897, an oral, small molecule designed to block CCR1, is a chemokine receptor believed to play a role in a number of inflammatory disorders including RA. MLN3897 is part of the company's broad inflammation program that includes several product candidates.
"Although many patients with RA initially respond to standard disease-modifying antirheumatic drugs such as methotrexate or anti-tumour necrosis factor drugs to some degree, up to 70 per cent ultimately have an inadequate response," said Nancy Simonian, M.D., senior vice president, clinical, medical and regulatory affairs, Millennium. "Our hope for MLN3897 is to provide patients with a new and innovative therapy for treating this debilitating disease."
The multicenter study will assess the efficacy, safety and tolerability of MLN3897 in combination with methotrexate (MTX), a standard therapy for RA. Up to 186 patients with RA will be enroled in the study and must have been taking MTX for a minimum of six months prior to screening. Patients will continue the MTX regimen and will be randomized to receive MLN3897 or placebo. The primary endpoint of the study is ACR20 response rate, a standard clinical measurement for RA, which measures improvement in the number of tender and swollen joints and various levels of disease activity.
MLN3897 is part of Millennium's larger inflammatory development program that includes six product candidates and is one of several small molecules included in the company's small molecule inflammation collaboration with sanofi-aventis. MLN3897 (sanofi-aventis AVE9897) is an orally active, small molecule antagonist of CCR1, a chemokine receptor found on the surface of various cells in the immune system and involved in a number of inflammatory disorders. In the phase I studies, results showed MLN3897 to be well-tolerated and to exhibit dose dependent blockage of the CCR1 receptor. Since CCR1 is involved in the recruitment of white blood cells in response to sites of inflammation, effectively blocking CCR1 could have a significant effect on RA disease progression and other inflammatory diseases.
RA is a chronic, progressive, inflammatory disease of the articular joints that results in significant pain, stiffness and swelling and leads to degradation of the joint tissue. RA can cause permanent damage and deformities to joints, resulting in loss of function and ultimately leading to joint replacement surgery in some cases. In addition, some RA patients develop extra-articular manifestations such as rheumatoid nodules, interstitial lung disease and vasculitis.
According to the Arthritis Foundation, RA affects 2.1 million Americans and is about three times more common in women than men. Mortality rates for people with RA are double those of the general population. The cause of RA is not known, however, it is believed to be an autoimmune disease where the body's natural immune system attacks healthy joint tissue causing inflammation and subsequent joint damage.
Millennium and sanofi-aventis have an alliance focused on developing and commercializing small molecule drugs for the treatment of inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. MLN3897 (sanofi-aventis AVE9897) is one of several small molecules that are part of this collaboration, three of which are in the clinic.
Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company based in Cambridge, Massachusetts, markets Velcade (bortezomib) for Injection, a novel cancer product, and has a robust clinical development pipeline of product candidates. The company's research, development and commercialization activities are focused in two therapeutic areas: oncology and inflammation. By applying its knowledge of the human genome, understanding of disease mechanisms and industrialized drug discovery platform, Millennium is developing an exciting pipeline of innovative product candidates.