Ofatumumab (brand name: Arzerra; manufacturer: GlaxoSmithKline) is a human monoclonal antibody therapy that targets the protein CD20 on the surface of B-cells (a type of lymphocyte that plays a key role in immune response). Remember that our bodies naturally produce antibodies against bacteria, viruses, and other foreign organisms that invade and pose a threat to our bodies. Following the example of our bodies, drug makers have engineered antibodies designed to target the mechanisms that cause a variety of diseases, including MS. CD20 plays a key role in helping B-cells function in the immune response, so inhibiting CD20 depletes B-cells and limits their proinflammatory function.
How far along is ofatumumab in the development process?
Ofatumumab received FDA approval in 2009 for treatment of refractory chronic lymphocytic leukemia (CLL), meaning it is used in CLL cases that have not responded to standard chemotherapies, such as fludarabine or alemtuzumab. Ofatumumab has also received conditional approval in Europe for treatment of CLL. In addition to MS, ofatumumab is being tested for use in other cancers of the blood, as well as in rheumatoid arthritis.
What evidence do we have that ofatumumab works in MS?
Ofatumumab has been tested in people with relapsing-remitting MS (RRMS) in a small Phase 1/2 randomized, placebo-controlled study. The study randomly assigned participants to one of 3 doses of ofatumumab (100 mg, 200 mg, or 700 mg, given as 2 infusions separated by 2 weeks) or placebo. The primary efficacy endpoint (the measure used to determine the effectiveness of the medication) was the number of new gadolinium (Gd)-enhancing brain lesions as detected by magnetic resonance imaging (MRI). Ofatumumab (all dosing groups combined) resulted in significantly fewer new Gd-enhancing lesions compared with placebo. In fact, with ofatumumab, the risk for new Gd-enhancing lesions was reduced by 99% compared with placebo. Ofatumumab also resulted in similar significant reductions in MRI T2 lesions compared with placebo.
What are the most common adverse effects with ofatumumab?
There is limited information on adverse effects with ofatumumab in people with MS. In one study of ofatumumab in CLL, the most common adverse effects included infusion reactions (that occurred mostly with the first infusion and were less frequent with subsequent infusions), infections (pneumonia, upper respiratory tract, and bronchitis), anemia, respiratory effects (cough and shortness of breath), diarrhea, nausea, rash, fatigue, and fever.