Danish drugmaker Genmab AS and its partner GlaxoSmithKline plc submitted a biologics license application to the FDA for Arzerra (ofatumumab) to treat patients whose chronic lymphocytic leukemia (CLL) is resistant to previous therapies.

If approved, Arzerra would be the first anti-CD20 monoclonal antibody available for that patient population.

Less than 25 percent of patients with CLL respond to most current treatments, the companies said.

The BLA for Arzerra, an investigational monoclonal antibody that targets a membrane-proximal small loop epitope on the CD20 molecule on B-cells, is Genmab's first antibody filed with the FDA, said CEO Lisa Drakeman.

The BLA was based on an analysis that included 138 patients with CLL who showed limited or no response to treatment with fludarabine and alemtuzumab and patients refractory to fludarabine and considered inappropriate candidates for alemtuzumab due to bulky tumor masses in their lymph nodes, or bulky fludarabine refractory.

The primary endpoint of the Arzerra study was assessment of response. The overall response rate in fludarabine-alemtuzumab refractory patients treated with Arzerra as a single agent was 58 percent and 47 percent for the bulky fludarabine refractory group, the companies reported.

The most common adverse events were infusion reactions and infections. About 3 percent of patients experienced infusion reactions that were serious but manageable, the firms reported.

One case of progressive multifocal leukoencephalopathy, a rare brain infection resulting in death or causing severe disability, and one case of tumor lysis syndrome were reported in study participants.

Other adverse events included fever, cough, diarrhea, rash, low white-blood cell counts, fatigue, pneumonia, anemia, shortness of breath and nausea, which was observed in about 10 percent of patients.

Genmab and GSK said they are conducting additional studies of Arzerra in CLL and non-Hodgkin's lymphoma (NHL) settings.

A Phase III CLL front-line study is evaluating Arzerra combined with chlorambucil in patients with previously untreated CLL. An ongoing Phase II study will assess Arzerra in patients with Waldenstrom's macroglobulinemia, a rare type of slow-growing NHL.

The companies also are conducting a Phase II study is evaluating Arzerra plus chemotherapy in relapsed/refractory diffuse large B-cell lymphoma. Ofatumumab targets a membrane-proximal, small loop epitope (a portion of a molecule to which an antibody binds) on the CD20 molecule on B-cells. That epitope is different from the binding sites targeted by other CD20 antibodies.