FDA accepts Genmab's Investigational New Drug Application for active rheumatoid arthritis treatment

Genmab announced today the US Food and Drug Administration (FDA) accepted its Investigational New Drug Application (IND) to start a Phase I/II dose escalation trial for HuMax-CD20 to treat patients with active rheumatoid arthritis (RA) who have failed one treatment with one or more disease modifying anti-rheumatic drugs (DMARDs).

A total of 60 patients will be randomized into three cohorts each containing 20 patients. In each cohort 16 patients will receive two infusions of HuMax-CD20 (300, 700 or 1000 mg doses) and 4 patients will receive placebo given 14 days apart. All patients in the study will also receive methotrexate, a recognized treatment in the US for RA. Patients will be followed for 24 weeks to evaluate safety and efficacy and then every 12 weeks until B-cell counts return to baseline levels. Genmab plans to initiate the study during the early part of 2005.

HuMax-CD20 is a human antibody which is effective at binding to the disease target, and releases only very slowly from the target over time. In December 2004 Genmab presented positive data from a Phase I/II trial with patients with relapsed or refractory follicular lymphoma showing 55% of patients treated with HuMax(TM)-CD20 achieved a clinical response in the Phase I/II study, including two complete responses and one unconfirmed complete response for a 27% complete response rate. These responses were observed in 11 evaluable patients among the first 15 of the 40 patients included in this study at the week 11 evaluation point.

A Phase I/II trial to treat patients with Chronic Lymphocytic Leukemia is ongoing.

The CD20 antigen is a transmembrane protein on pre-B and mature B lymphocytes. CD20 appears to act as a calcium ion channel, and to regulate early steps in B lymphocyte activation. The molecule is not shed from the cell surface, and is not internalized upon antibody binding. CD20 is found on over 90% of B-cell lymphomas, as well as other lymphoid tumors of B-cell origin.

Rheumatoid arthritis (RA) is a systemic inflammatory disease which affects 0.8-1.0% of all populations. The aetiology of RA remains unknown.