The Food and Drug Administration (FDA) has approved Briumvi (ublituximab-xiiy) for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Ublituximab-xiiy is a glycoengineered monoclonal antibody that targets CD20, a cell surface antigen present on pre-B and mature B lymphocytes. Following cell surface binding to B lymphocytes, ublituximab-xiiy results in cell lysis through mechanisms including antibody-dependent cellular cytolysis and complement-dependent cytolysis. Glycoengineering is expected to enhance the potency of ublituximab. 

The approval was based on data from the phase 3 ULTIMATE I (ClinicalTrials.gov Identifier: NCT03277261) and ULTIMATE II (ClinicalTrials.gov Identifier: NCT03277248) trials, which evaluated the efficacy and safety of ublituximab-xiiy vs teriflunomide in patients with relapsing multiple sclerosis. Patients were randomly assigned to receive either ublituximab-xiiy 150mg via intravenous infusion on day 1 and 450mg on day 15, followed by a 450mg dose every 6 months or teriflunomide 14mg orally, once daily.

Results from both trials showed that treatment with ublituximab-xiiy demonstrated a statistically significant reduction in annualized relapse rate (ARR) over a 96-week period compared with teriflunomide (primary endpoint). In ULTIMATE I, treatment with ublituximab-xiiy resulted in an ARR of 0.076 vs 0.188 for teriflunomide, representing a relative reduction of 59% (P <.001). In ULTIMATE II, treatment with ublituximab-xiiy resulted in an ARR of 0.091 vs 0.178 for teriflunomide, representing a relative reduction of 49% (P =.002).

Additionally, ublituximab-xiiy statistically significantly reduced the number of T1 Gd-enhancing lesions and the number of new or enlarging T2 lesions in both studies compared with teriflunomide:

  • Mean number of T1 Gd-enhancing lesions per MRI: 0.016 vs 0.491 (relative reduction, 97%; P <.001) in ULTIMATE I; 0.009 vs 0.250 (relative reduction, 97%; P <.001) in ULTIMATE II.
  • Mean number of new or enlarging T2 hyperintense lesions per MRI: 0.213 vs 2.789 (relative reduction, 92%; P <.001) in ULTIMATE I; 0.282 vs 2.831 (relative reduction, 90%; P <.001) in ULTIMATE II.

“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 3 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,” said Lawrence Steinman, MD, Zimmermann Professor of Neurology & Neurological Sciences, and Pediatrics at Stanford University and principal investigator for both trials. “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.”

The most common adverse reactions reported with treatment included infusion reactions and upper respiratory tract infections.

Briumvi is supplied as a 150mg/6mL single-dose vial containing a preservative-free solution for intravenous use. The product is expected to be available in the first quarter of 2023.

References

  1. TG Therapeutics announces FDA approval of Briumvi (ublituximab-xiiy). News release. TG Therapeutics. December 28, 2022. Accessed December 29, 2022. https://www.globenewswire.com/news-release/2022/12/28/2580377/8790/en/TG-Therapeutics-Announces-FDA-Approval-of-BRIUMVI-ublituximab-xiiy.html.
  2. Briumvi. Package insert. TG Therapeutics; 2022. Accessed December 29, 2022. https://www.tgtherapeutics.com/label-prescribing-info/uspi-briumvi.pdf.