Intravenous formulation nixed, and MS trial with subcutaneous version will start next year.
GlaxoSmithKline (GSK) and Genmab have agreed to refocus the development of ofatumumab for autoimmune indications. The tweak to their collaboration agreement means GSK will now concentrate on the development of subcutaneously delivered ofatumumab for autoimmune disorders and stop development of intravenously delivered ofatumumab for these diseases.
The firms have in addition confirmed that based on recently reported positive data from the Phase II trial evaluating infused ofatumumab in multiple sclerosis (MS) patients, GSK aims to start a Phase IIb dose-ranging MS trial using subcutaneously administered ofatumumab in 2011. Further work on subcutaneously delivered ofatumumab for rheumatoid arthritis (RA) therapy is separately under review, the companies admit.
“Although the intravenous delivery of ofatumumab has previously demonstrated positive results in MS and RA studies, the autoimmune program is being refocused on the subcutaneous delivery of ofatumumab because GSK believes this route of administration has the potential to offer added convenience and improved tolerability,” comments Ian Tomlinson, senior vp of biopharmaceuticals R&D at GSK.
Results from the Phase I/II MS trial were reported on September 10. The double-blind, dose-escalation, safety, and pharmacokinetics trial evaluated ofatumumab in 38 patients with relapsing-remitting MS. Patients were randomized to receive two infusions of 100 mg, 300 mg, or 700 mg of ofatumumab or placebo. After 24 weeks, the patients randomized to placebo were treated with ofatumumab and those patients initially treated with ofatumumab were switched to placebo. All patients were then followed for an additional 24 weeks. The firms said the resulting data identified no dose-limiting toxicities and no unexpected safety findings. None of the patients tested positive for human antihuman antibodies. Repeated MRI scans in addition showed a sustained reduction in the number of brain lesions up to week 48 in patients who were treated with ofatumumab followed by placebo. Patients who received placebo followed by ofatumumab showed similar 24 week results.
Ofatumumab is a fully human antibody targeting the CD20 molecule in the cell membrane of B-cells. The drug is being developed by Genmab and GSK under a worldwide co-development and commercialization agreement. Tradenamed Arzerra®, ofatumumab has received FDA accelerated approval for patients with chronic lymphocytic leukemia that is refractory to fludarabine and alemtuzumab. In April the European Commission separately granted a conditional marketing authorization for use of ofatumumab in equivalent patients in Europe.