PHILADELPHIA—Ofatumumab reduces new T1 gadolinium-enhancing lesions by more than 90%, compared with placebo, among patients with relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The monoclonal antibody appears to deplete B cells in a dose-dependent manner.
Investigators found no difference between drug and placebo in the rate of adverse events, and the majority of the adverse events were mild to moderate. The most common adverse events were injection-related reactions.
Ofatumumab is a fully human anti-CD20 monoclonal antibody that binds even at low levels of CD20. The drug “induces B cell lysis quite efficiently, primarily through antibody-dependent cellular cytotoxicity,” said Amit Bar-Or, MD, Professor of Neurology and Neurosurgery at McGill University in Montreal. Ofatumumab is indicated for the treatment of chronic lymphocytic leukemia.
Amit Bar-Or, MD
Comparing Doses of Ofatumumab
Dr. Bar-Or and colleagues conducted a placebo-controlled trial to determine the MRI efficacy, tolerability, and safety of subcutaneous injections of ofatumumab in patients with relapsing-remitting MS. The study’s primary end point was the cumulative number of new T1 gadolinium-enhancing brain lesions at 12 weeks.
The researchers randomized 231 individuals with relapsing-remitting MS to either placebo, 3 mg of ofatumumab every three months, 30 mg of ofatumumab every three months, 60 mg of ofatumumab every three months, or 60 mg of ofatumumab every month. The study began with a 24-week double-blind treatment phase, followed by a 20-week individualized follow-up phase. Dr. Bar-Or reported on the primary outcome as assessed at week 12.
Eligible patients were between ages 18 and 55 and had an Expanded Disability Status Scale score between 0 and 5.5. Baseline patient characteristics were well balanced among the study groups with respect to sex, race, age, and disease duration. At baseline, patients’ number of relapses within the past 24 months ranged from 1.7 to 1.9. More than 90% of participants completed the 24-week treatment phase of the study.
Ofatumumab Reduced New Lesions by More Than 90%
The dosing regimens were associated with a dose-dependent decrease in circulating B cells, and mathematical modeling indicated that a 50% decrease in B cells would be expected with a dose of less than 3 mg of ofatumumab. Individuals who received 3 mg of drug every three months had a 70% reduction in new gadolinium-enhancing lesions, relative to controls. New gadolinium-enhancing lesions in the brain were reduced by more than 90%, relative to controls, in patients who received the three dose regimens of 30 mg of ofatumumab or more.
Over the 24-week treatment phase, six adverse events led to withdrawal from the study (all of these occurring in the treatment arms). The investigators found no differences in the rate of infectious adverse events between the study groups, including placebo treated. Infectious adverse events included nasopharyngitis, urinary tract infection, and respiratory tract infection, but these outcomes were infrequent “and no different from what we have seen in prior anti-CD20–depleting regimens,” said Dr. Bar-Or.
Injection-Related Reactions Were the Most Common Adverse Events
Five individuals had serious adverse events during the first 12 weeks. Another serious adverse event occurred between weeks 12 and 24. The serious adverse events included injection-related reactions, cholelithiasis, cytokine release syndrome, and hypokalemia. Four of these events occurred in patients receiving 60 mg of ofatumumab every month.
“There was no evidence of clinically meaningful changes in laboratory parameters or vital signs,” said Dr. Bar-Or. “There was no evidence of clinically meaningful immunogenicity, including development of human antihuman antibodies, which occurred in only four individuals at low levels and did not appear to impact treatment effect. There were no cases of opportunistic infections, including progressive multifocal lleukoencephalopathy.”
—Erik Greb