Antiangiogenic Role Of 2ME2 Demonstrated In Rheumatoid Arthritis Models

Ruzanna Harutyunyan's picture
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EntreMed, Inc. (Nasdaq: ENMD), a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, today announced the publication of preclinical results for 2ME2 (Panzem or 2-methoxyestradiol) in rheumatoid arthritis (RA). The results of the study, conducted by EntreMed collaborator, Dr. Ernest Brahn, Professor of Medicine, Rheumatology Program Director, David Geffen School of Medicine at UCLA, were published in the November 2008 issue of the Journal of Rheumatology (Brahn E, Banquerigo ML, Lee JK, Park EJ, Fogler WE, and Plum SM. An angiogenesis inhibitor, 2-methoxyestradiol, involutes rat collagen-induced arthritis and suppresses synovial VEGF and bFGF gene expression. J Rheumatol 2008;35:2119- 28).

Results from treatment studies in a preclinical model of established rheumatoid arthritis demonstrated that daily oral administration of 2ME2 suppressed both clinical and radiographic indicators of joint inflammation and damage, including soft tissue swelling and bone erosion. The treatment benefits of 2ME2 were dose-dependent and associated with reduced joint expression of the prominent angiogenic growth factors, FGF-2 and VEGF, as well as decreased angiogenesis. The report further demonstrates both a delay in onset and decrease in severity of arthritis if 2ME2 treatment is started prior to disease initiation. These results indicate that 2ME2 may represent a novel agent for treatment of inflammatory autoimmune diseases such as rheumatoid arthritis and identify 2ME2 as a disease modifying anti-rheumatic drug (DMARD).

Dr. Brahn commented on the outcome of the study, "These results demonstrate the beneficial effect of 2ME2 in managing disease progression in preclinical models of rheumatoid arthritis. Furthermore, these results indicate that 2ME2 may represent a novel agent for the treatment of rheumatoid arthritis through its inhibitory activity on inflammation and angiogenesis."

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Kenneth W. Bair, Ph.D., EntreMed Senior Vice President, Research & Development, further commented, "These data continue to support the potential therapeutic benefit of 2ME2 for the treatment of inflammatory diseases such as rheumatoid arthritis. 2ME2 is an oral, small molecule, disease-modifying anti- rheumatic drug with an excellent safety profile established through daily dosing in more than 300 cancer patients, some for over 5 years. The Company has initiated clinical activities to support 2ME2 in RA, including the completion of a healthy volunteer study. Results of the healthy volunteer study have been submitted to the FDA and, once feedback has been received, we will determine the appropriate next steps for continuing the 2ME2 RA clinical program."

About Rheumatoid Arthritis

Rheumatoid arthritis affects over 2 million American adults, of which about two-thirds of them are women. The disease, characterized by pain, stiffness, swelling, and deformity can become debilitating. Within 5 years of diagnosis, a third of patients are no longer working, and within 10 years, half of the patients have substantial functional disability. RA can shorten life expectancy by 5-10 years.

Rheumatoid arthritis, one of the most common forms of arthritis, is a systemic disease characterized by inflammation of the membrane lining of the joint, which causes pain, stiffness, redness, swelling, and loss of function in the joint. The inflamed joint lining, called the synovium, releases enzymes that destroy bone and cartilage, causing the joint to lose its shape and alignment. This process can result in joint pain, loss of movement, and deformity. DMARDs are drugs that have the ability to slow down disease progression in rheumatoid arthritis and other autoimmune diseases.

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