A total of 225 patients with active RA that is refractory to one or more disease-modifying antirheumatic drugs (DMARDs) were enrolled in this double-blind, placebo-controlled study to evaluate the safety and efficacy of ofatumumab. Patients were randomized to one of four treatment groups (300 mg, 700 mg, or 1000 mg ofatumumab, or placebo) and assessed on the basis of their American College of Rheumatology (ACR) and EULAR responses at 24 weeks. Continuation of current stable doses of methotrexate (MTX) and low dose corticosteroids were permitted.

In the intention-to-treat study population, comprising 224 patients, ACR20 in was achieved by 46%, ACR50 was achieved by 24%, and ACR70 achieved by 6% of ofatumumab patients compared with 15%, 5%, and 0% in the placebo group. Evaluated by the three ofatumumab dose groups, ACR20 was obtained by 41% (P = .002), 49% (P <.001), and 46% (P <.001) of patients; ACR50 was obtained by 19%, 26% and 26%; ACR70 was obtained by 9%, 4% and 6%. These scores indicate a 20%, 50%, or 70% improvement respectively in the number of swollen and tender joints, as well as improvements in other disease-activity measures.

In a subgroup of 178 patients receiving concomitant stable doses of MTX across the 300 mg, 700 mg, and 1000 mg ofatumumab doses, results showed that an ACR20 response was obtained by 42% (P = .006), 56% (P <.001), and 50% (P = .001), respectively, compared with 16% in the placebo group. An ACR50 response was obtained by 21%, 26%, and 26% of patients receiving the varying doses of ofatumumab, with 8%, 2%, and 5% obtaining an ACR70 response. The corresponding responses for the placebo group were 7% and 0%.

The patients' immune responses to study medication (ofatumumab or placebo) were also evaluated by testing for the presence of human antihuman antibodies (HAHAs). All patients tested negative at 24 weeks.

Overall, at week 24, 72% (300 mg, P <.001; 700 mg, P = .001; 1000 mg, P = .001) of patients treated with each of the ofatumumab doses experienced at least a moderate or good EULAR response compared with 40% of patients receiving placebo.

The data also showed that ofatumumab appeared well tolerated, with no increased frequency of serious infections. Approximately half of the adverse events occurred on infusion days (51%).
 
For Genmab, the total potential value of the codevelopment agreement in cancer and various autoimmune and inflammatory diseases, in the event of full commercial success, could exceed US$2.1 billion. In addition, Genmab will be entitled to receive tiered double-digit royalties on global sales of HuMax-CD20.

—A. Techman

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