REPORT FROM THE AMERICAN ACADEMY OF NEUROLOGY (AAN) ANNUAL MEETING, PHILADELPHIA PA, APRIL 26-MAY 3, 2014 – Preliminary results are available for two novel MS therapies that are currently in development.

Ofatumumab (Arzerra) is the latest in a series of anti-CD20 monoclonal antibodies (after rituximab and ocrelizumab) that targets B cells in MS. The MIRROR phase II trial (NCT01457924) is a 6-month dose-ranging study assessing four different dosing regimens in 232 MS patients (Bar-Or et al. AAN 2014; abstracts S23.006 and I7-1.007). Subjects were randomized to placebo or subcutaneous ofatumumab 3 mg, 30 mg or 60 mg every 12 weeks, or ofatumumab 60 mg every four weeks. At 12 weeks, the placebo group received ofatumumab 3 mg. At weeks 4-12, there was an estimated >90% reduction in the cumulative number of new T1 gadolinium-enhancing lesions in groups receiving at least 30 mg. The most common adverse effects were injection-related reactions (oftatumumab 52% vs. placebo 15%); the rate of infections (e.g. UTI, respiratory tract infections) was low. An interesting finding was that intermediate levels of B cell depletion could be achieved, suggesting that clinical efficacy may be attained while preserving some degree of B cell function.

Pixantrone is structurally similar to mitoxantrone but is reported to be less cardiotoxic. A phase I/II trial of pixantrone in 18 patients with aggressive MS reported that the annual relapse rate was reduced from 1.67 to 0.22 at 12 months; EDSS was stabilized (3.58 vs. 3.92 at baseline) (Gonsette et al. AAN 2014; abstract P3.170). The mean number of Gd-enhancing lesions was reduced 88% at three months and 86% at 12 months compared to baseline. Neutropenia occurred in 53% of patients after each infusion but neutrophil recovery was seen in all patients at one month post-infusion. B cells were reduced 95% at month 3, and by 47% at month 12. T cells showed a transient 33% reduction. Left ventricular ejection fraction was stable (64% at baseline, 62% at month 12). However, one patient had an early, rapid decrease in LVEF and one patient had  transient LVEF < 50% at month 6.

Guest Reviewer: Dr. Daniel Selchen, Head of Neurology, St. Michael’s Hospital, Toronto, Canada