A drug that inhibits early-stage B-lymphocyte activation reduced disease activity in patients with relapsing-remitting multiple sclerosis, and showed potential to significantly decrease the annual number of new brain lesions.
The "intriguing" early results of a phase II randomized study suggest that ofatumumab’s targeting of peripheral B cells may be beneficial in treating the disease, according to Daren Austin, Ph.D., head of biopharm clinical pharmacology and biometrics at GlaxoSmithKline, Uxbridge, U.K. He will present these data Wednesday, April 30, at the annual meeting of the American Academy of Neurology.
"These results need to be validated, of course, but the findings are interesting," Dr. Austin said in a press statement. "They provide new insight into the mechanism of B cells in MS [multiple sclerosis] and present a possible new target threshold for exploring the potential benefit of anti-B-cell therapy."
Ofatumumab (Arzerra) is a fully humanized monoclonal antibody against B-lymphocyte antigen CD20, which optimizes B-cell antibody response. On April 17, the U.S. Food and Drug Administration approved the agent for use in combination with chlorambucil in previously untreated patients with chronic lymphocytic leukemia, for whom fludarabine-based therapy is considered inappropriate.
The drug also has shown potential in treating follicular non-Hodgkin’s lymphoma, diffuse large B-cell lymphoma, and rheumatoid arthritis.
The data Dr. Austin will report are part of an ongoing dose-ranging evaluation of 3 to 180 mg of ofatumumab for relapsing-remitting MS. The drug is administered by subcutaneous injection.
The current study included 231 patients who were randomized to placebo or ofatumumab for 24 weeks. The primary endpoint was the correlation of CD19 B-cell count to new gadolinium-enhancing brain lesions (a proxy measure for disease activity). Brain imaging was conducted every 4 weeks throughout the trial.
All of the groups – including placebo – showed lesion activity in the first 4 weeks. However, patients in the active groups showed some lesion suppression after that time. The beneficial effect seemed to appear when patients’ CD19 count fell below 64 cells/mcL, Dr. Austin said.
Researchers correlated B-cell levels to the total number of new brain lesions that appeared on magnetic resonance imaging. If CD19 levels were maintained in the range of 32-64 cells/mcL, patients taking the drug would develop fewer than 1 new lesion per year, compared with 16 new lesions per year in untreated patients, Dr. Austin said in the statement.
The most common side effects, which occurred twice as often in the active group as in the placebo group, were injection-site reaction, dizziness, anxiety, fever, respiratory tract infection, and neuropathy.
Ofatumumab is not approved anywhere in the world for use in the treatment of MS, Dr. Austin added.
GlaxoSmithKline sponsored the study. Dr. Austin is an employee of the company.