GlaxoSmithKline (GSK) and Genmab A/S announced topline results from the concluded pivotal trial of ofatumumab in patients with fludarabine and alemtuzumab refractory chronic lymphocytic leukaemia (CLL).

Ofatumumab was given accelerated approval by the US Food and Drug Administration (FDA) on October 26, 2009 for the treatment of patients with CLL who are refractory to fludarabine and alemtuzumab treatment based on the interim results from this trial in 59 patients. On April 19, 2010, the European Commission granted a conditional marketing authorization to Arzerra (ofatumumab) for the treatment of chronic lymphocytic leukaemia (CLL) in patients who are refractory to fludarabine and alemtuzumab.

A total of 95 patients with fludarabine and alemtuzumab refractory CLL were treated in the study. The objective response rate (ORR), as determined by an Independent Review Committee, in the study was 51 per cent. In addition to the 95 patients in the efficacy analysis the study also included 128 patients with relapsed or refractory CLL, who were not refractory to both fludarabine and alemtuzumab.

There were no unexpected safety findings reported with the total study population (n=223). The most common adverse reactions (?10%) occurring in patients treated with Arzerra were pyrexia (21%), anaemia (18%), diarrhoea (17%), neutropenia, fatigue (16%), dyspnea (15%), pneumonia (15%), chills (13%), rash (13%), nausea (13%), bronchitis (12%), peripheral edema (11%), back pain (10%) and upper respiratory tract infection (10%).

Results from this concluded pivotal trial are consistent with the efficacy and safety data reported in the interim analysis and demonstrate the activity of single-agent ofatumumab in patients with heavily pretreated fludarabine and alemtuzumab-refractory chronic lymphocytic leukaemia.

Ofatumumab is a human monoclonal antibody. Ofatumumab binds specifically to both the small and large extracellular loops of the CD20 molecule. The CD20 molecule is expressed on normal B lymphocytes (pre-B- to mature B-lymphocytes) and on B-cell CLL. In vitro data suggest that possible mechanisms of cell lysis include complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.