Anticancer agent - ofatumumab
One of the more successful monoclonal antibody drugs for treating cancer has been MabThera (rituximab), an anti-CD20 mAB that is extremely effective in treating B cell malignancies such as non-Hodgkin's lymphoma in combination with more conventional chemotherapy drugs such as doxorubicin, vincristine and cyclophosphamide.
One of the more successful monoclonal antibody drugs for treating cancer has been MabThera (rituximab), an anti-CD20 mAB that is extremely effective in treating B cell malignancies such as non-Hodgkin's lymphoma in combination with more conventional chemotherapy drugs such as doxorubicin, vincristine and cyclophosphamide.
However, it works less well as monotherapy, and another promising anti-CD20 mAB, ofatumumab, is being developed by Genmab in collaboration with GlaxoSmithKline, which appears to have a better binding profile and cytotoxicity than rituximab.1
In an open label, dose escalation, multicentre Phase I/II study, 40 patients with relapsed or refractory follicular non-Hodgkin's lymphoma were given four weekly intravenous infusions of 300, 500, 700 and 1000mg of the drug.2 No dose limiting toxicities were seen, and the maximum tolerated dose was not reached either. It induced objective responses at all of the doses, and also in patients who had previously been treated with rituximab. Most adverse events were cytokine release-related, including fever, nausea, rash, fatigue and pruritis.
The drug has also been investigated in chronic lymphocytic leukaemia.3 A total of 33 patients were given an intravenous infusion of 100, 300 or 500mg of ofatumumab, followed by three further infusions of 500, 1000 or 2000mg. The patients were followed up for 12 months, adverse events were mainly seen on the infusion days, and again were largely related to cytokine release. It reduced the CD19+/CD5+ counts in all subjects, and 11 achieved a partial response.
Another potential indication is rheumatoid arthritis. A total of 39 patients who had failed at least one disease modifying antirheumatic drug were given two intravenous infusions of 300, 700 or 1000mg of ofatumumab.4 Again, the maximum tolerated dose was not reached, and it proved effective in inducing clinical responses, with rapid and sustained CD19+ depletion being seen at all three doses.
Several Phase II and III trials are under way, including one looking at it in combination with cyclophasphamide and fludaribine, and several more as a single agent.