FDA Approves Monoclonal Antibody for Treating Relapsing MS  

The Food and Drug Administration (FDA) approved ublituximab (Briumvi; TG Therapeutics, New York, NY) for treating relapsing forms of multiple sclerosis (MS) in adults, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.    

The approval is based on data from the phase 3 ULTIMATE I and II trials (NCT03277261 and NCT03277248), which showed that ublitumixab was more effective when compared with teriflunomide in reducing the annualized relapse rate (ARR)---the primary endpoint of the studies. In addition, data indicated that participants treated with ublitumixab experienced significantly fewer T1 Gd-enhancing lesions and new or enlarging T2 lesions compared with those treated with teriflunomide.

These results represent the first phase 3 research of an anti-CD20 monoclonal antibody for relapsing MS to produce an ARR of less than 0.10, which translates into less than 1 relapse in 10 years.

“Over the past several years we have seen a dramatic shift in the MS treatment landscape towards the use of B-cell therapy, which has shown to be highly effective in reducing relapses in patients,” said Lawrence Steinman, MD, Zimmermann professor of Neurology & Neurological Sciences and Pediatrics, Stanford University. 

ULTIMATE I and ULTIMATE II were randomized, double-blind clinical trials of identical design that enrolled a total of 1,094 individuals who had experienced previous relapses or who had a T1 Gd-enhancing lesion in the previous year. Participants were treated for 96 weeks and were randomized to receive either ublituximab as an IV infusion with an oral placebo given daily or oral teriflunomide (14 mg) given daily with an IV placebo administered on a staggered schedule. The first infusion of ublituximab was 150 mg given in 4 hours; the second infusion was 450 mg given in 1 hour, 2 weeks after the first infusion; and the third infusion was 450 mg given in 1 hour, every 24 weeks. 

Adverse reactions to ublituximab include infusion reactions, upper and lower respiratory tract infections, pain in extremities, insomnia, and fatigue.