FDA approves ublituximab for relapsing multiple sclerosis

The Food and Drug Administration (FDA) approved ublituximab for the treatment of relapsing forms of multiple sclerosis (MS), making it the first anti-CD20 monoclonal antibody approved that can be administered in a one-hour infusion twice-a-year following the starting dose.

Ublituximab is a monoclonal antibody targeting a unique epitope on CD20-expressing B-cells and is glycoengineered for enhanced antibody-dependent cellular cytotoxicity (ADCC), which allows for efficient B-cell depletion at low doses. On December 28, 2022, the anti-CD20 antibody received FDA approval based on results from the Phase III ULTIMATE I and II trials (NCT03277261; NCT03277248).1 These were two identical, double-blind, double-dummy trials in which a total of 1094 participants with relapsing MS were randomly assigned to receive intravenous ublituximab (150 mg on day 1, followed by 450 mg on day 15 and at weeks 24, 48, and 72) and oral placebo or oral teriflunomide (14 mg once daily) and intravenous placebo. The two trials assessed the annualized relapse rate (ARR) as the primary endpoint, and the secondary endpoints included the number of gadolinium-enhancing lesions on magnetic resonance imaging (MRI) by 96 weeks and worsening of disability.2

The results published in the New England Journal of Medicine showed that the AAR in the ULTIMATE I trial was 0.08 with ublituximab and 0.19 with teriflunomide (rate ratio, 0.41; 95% CI, 0.27 to 0.62; P<0.001); in the ULTIMATE II trial, the AAR was 0.09 and 0.18, respectively (rate ratio, 0.51; 95% CI, 0.33 to 0.78; P=0.002).2

Treatment with ublituximab was also associated with significant reductions in the number of gadolinium-enhancing lesions compared with the teriflunomide group (ULTIMATE I: P<0.001; ULTIMATE II: P<0.001). Additionally, in the pooled analysis, 5.2% of the patients on ublituximab had worsening of disability at 12 weeks compared with 5.9% of those on teriflunomide (hazard ratio, 0.84; 95% CI, 0.50 to 1.41; P=0.51). Safety data shows that ublituximab was associated with infusion-related reactions, which occurred in 47.7% of the patients in the ublituximab group, and serious infections were also higher in the ublituximab group (5.0% vs. 2.9%).2

Principal investigator, Lawrence Steinman, MD, Stanford University, Stanford, CA, said in a press release, “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. The outcome of the ULTIMATE I & II trials evaluating ublituximab, a novel targeted anti-CD20 agent designed for efficient B-cell depletion that supported this approval, represents an important milestone in the history of MS research as the first Phase III study of an anti-CD20 monoclonal antibody in patients with relapsing MS to produce an annualized relapse rate of less than 0.10, which translates to less than 1 relapse in 10 years. This approval is great news for patients living with MS and provides an appealing treatment alternative that can be administered in a one-hour infusion twice-a-year following the starting dose, which I believe is an added benefit to patients.”1

In an interview with VJNeurology, Dr Steinman added, “It’s very reassuring to individuals to know that not only does disease get stabilized [with ublituximab], but there’s an actual improvement, and that’s something we all hope to be able to have for individuals with MS.”

Ublituximab should be available in the first quarter of this year. Its unique attributes, particularly its ability to be infused in a one-hour infusion every six months following the first dose, will offer benefits to patients with relapsing forms of MS.

Written by Marta Palhas


  1. TG Therapeutics. TG Therapeutics Announces FDA Approval of BRIUMVI™ (ublituximab-xiiy). [Press Release]. Dec 2022. (Last accessed: 9 January 2023)
  2. Steinman L, Fox E, Hartung HP, et al. Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis. N Engl J Med 2022; 387:704-714.