Arzerra™ Approved for Refractory Chronic Lymphocytic Leukemia

The targeted therapy Arzerra™ (ofatumumab) has been granted accelerated approval by the U.S. Food and Drug Administration for treatment of patients with chronic lymphocytic leukemia (CLL) that is refractory to Fludara® (fludarabine) and Campath® (alemtuzumab).[1]

Arzerra inhibits early-stage B lymphocyte activation. It is under development for treatment of B-cell lymphoid malignancies and rheumatoid arthritis. A Phase I-II study was carried out in 33 patients with refractory B-cell CLL.[2] A maximum tolerated dose was not reached in this study. Toxicities were related to early infusions, which diminished with further infusions. More than half the patients developed infections, with one fatal interstitial pneumonia. The response rate was 50%. A second Phase I-II study was carried out in 40 patients with refractory follicular lymphoma treated at four different dose levels of Arzerra.[3] Patients in this study had “profound” B-cell depletion, and 65% reverted to a BCL2 negative status. Response rates ranged from 20% to 63%. The median response duration for responders was 30 months

The basis for FDA approval of Arzera was an international Phase II study that reported that Arzerra was effective for the treatment of patients with CLL who have failed Fludara and Campath (double refractory) or who had failed Fludara and had bulky disease.[4] This study involved 138 patients who were refractory to Fludara and Campath (n=59) or were refractory to Fludara and had bulky disease (n=79). In double-refractory patients, the overall response rate was 54% in patients with any prior exposure to Rituxan and 63% in patients who had no prior exposure to Rituxan. These authors concluded: “Single-agent therapy with ofatumumab is effective in patients with doubly refractory or bulky fludara refractory CLL.” The most common serious side effects of Arzerra were infections, neutropenia, and fever.

Comments: These data confirm that many patients with refractory CLL who have failed Fludara, Campath, and Rituxan therapy will respond to Arzerra.

[1] Genmab and GSK press release. GSK Web site. GSK and Genmab receive accelerated approval for ARZERRA™. Available at: http://www.gsk.com/media/pressreleases/2009/2009_us_pressrelease_10077.htm. Accessed October 28, 2009.

[2] Coiffier B, Lepretre S, Pedersen LM, et al. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B0cell chronic lymphocytic leukemia: a phase 1-2 study. Blood. 2008;111:1094-1100.

[3] Hagenbeck A, Gadeberg O, Johnson P, et al. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood. 2008;111:5486-5495.

[4] Wierda WG, Kipps T, Mayer J, et al. Activity of ofatumumab, a novel CD20 mAB, and prior rituximab exposure in patients with fludarabine- and alemtuzumab-refractory or bulky fludarabine-refractory chronic lymphocytic leukemia (CLL). Journal of Clinical Oncology. 2009;27:15s, abstract number 7044.