Genmab A/S, of Copenhagen, Denmark, reported encouraging safety and efficacy data from its 24-week multicenter, double-blind, randomized, placebo-controlled, dose-escalation phase I/II study of HuMax-CD20â„¢ in patients with active RA who have failed treatment with one or more disease-modifying antirheumatic drugs (DMARDs). HuMax-CD20 is a fully human, high-affinity IgG1 antibody targeted at the CD20 molecule of B cells.

In the study of 39 patients, 33 received either two infusions of HuMax-CD20 (300 mg, 700 mg, and 1000 mg) or placebo, given 2 weeks apart. Twenty-six of the 39 had previously received treatment with tumor necrosis factor (TNF)-alpha inhibitors. Twenty-two were intolerant or refractory to TNF-alpha inhibitors, and four stopped for other reasons. Efficacy among these patients was in the same range as for the rest of the group on an intent-to-treat basis. A satisfactory safety profile was demonstrated, with the majority of adverse events occurring at the first infusion. An immediate, significant, and long-lasting B-cell depletion occurred at all dose levels.

In August 2005, Genmab announced the expansion of the phase I/II study into a phase II trial, which will include 200 additional patients randomized into four treatment groups. Fifty patients in each group will receive two infusions of either 300, 700, or 1000 mg of HuMax-CD20 or placebo. The doses will be given 2 weeks apart. Patients receiving a stable dose of methotrexate between 7.5 mg and 25 mg per week at the time of screening will continue with the regimen. 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. To date, 101 patients have received treatment with HuMax-CD20 in the ongoing phase II study.  

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. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B cells to regenerate after treatment and return to normal levels within several months.

— A. Techman