Positive Early-Phase Results for Ofatumumab in MS

Susan Jeffrey

October 11, 2013

Positive topline results of a phase 2 study suggest treatment with ofatumumab (Arzerra, Genmab) reduced the number of new gadolinium-enhancing lesions with all doses of the drug vs placebo in patients with relapsing-remitting multiple sclerosis (MS), the company reports.

The drug is a human monoclonal antibody that targets an epitope on the CD20 molecule encompassing parts of the small and larger extracellular loops. Already approved for chronic lymphocytic leukemia (CLL) in patients with further disease after treatment with fludarabine and alemtuzumab, it is being developed for autoimmune diseases under a codevelopment and collaboration agreement between Genmab and GlaxoSmithKline (GSK). In CLL, it is given intravenously, but it has been reformulated as a subcutaneous injection for the treatment of MS.

This phase 2, multicenter, double-blind, placebo-controlled study carried out by GSK randomly assigned 232 patients with relapsing-remitting MS to receive ofatumumab, 3 mg, 30 mg, or 60 mg, subcutaneously every 12 weeks, 60 mg every 4 weeks, or placebo, followed by 3 mg of ofatumumab at week 12.

The primary endpoint was reduction in the number of new T1-weighted gadolinium-enhancing lesions. The treatment period for all patients was 24 weeks. Participants were then followed until B-cell repletion for at least an additional 24 weeks. "Currently, all subjects have completed the 24-week treatment period; some subjects continue to be followed as per protocol," the announcement said.

Results showed "a clear separation" from placebo on the cumulative number of new active lesions over 12 weeks with all doses of ofatumumab (P < .001), the company reports. Data from weeks 0 to 12 estimated a 65% reduction in new T1 gadolinium-enhancing lesions for all doses (P < .001). "In weeks 4 to 12, analyses of data estimated a ≥90% reduction in the cumulative number of new T1 gadolinium-enhancing lesions for all cumulative doses of ofatumumab ≥30 mg (P < .001)," the statement adds.

There were no unexpected safety findings in the study, the company reports. Between weeks 0 and 12, injection-related reactions were the most common adverse reaction, seen in 52% of patients receiving ofatumumab vs 15% of those receiving placebo. Five serious adverse events were reported, all in patients receiving the 60-mg dose, but none of these patients withdrew from the study.

Twelve patients did withdraw during the study, and 10 of these were receiving ofatumumab. "To date, no cases of progressive multifocal leukoencephalopathy (PML) or opportunistic infections have been observed," the statement notes.

"We are encouraged by the results from this study, which we believe underline the potential of subcutaneous ofatumumab for treatment of relapsing-remitting multiple sclerosis," said Jan van de Winkel, PhD, chief executive officer of Genmab.

The US Food and Drug Administration (FDA) recently granted ofatumumab breakthrough therapy designation in the treatment of CLL for use in combination with chlorambucil for treatment-naive patients who are not candidates for fludarabine-based therapy.

Breakthrough therapy designation was enacted last year as part of the 2012 FDA Safety and Innovation Act and is the newest FDA initiative for accelerating the development and review of drugs. This designation is meant for an agent to be used alone or in combination with 1 or more other drugs to treat a serious or life-threatening disease or condition. It includes all the features of the fast-track designation but has more intensive guidance from the FDA on the drug's clinical development program.

On September 25, the FDA added a boxed warning about the risk for reactivation of hepatitis B virus infection in patients who once had the virus to the product labeling for 2 drugs used for treating hematologic malignancies, ofatumumab and rituximab (Rituxan, Genentech/Biogen IDEC).

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