Currently Enrolling Trials
Briumvi (ublituximab-xiiy) is a CD20-directed cytolytic antibody.
Briumvi is specifically indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
Briumvi is supplied as a solution for intravenous administration.
- HBV reactivation occurred in an MS patient treated with Briumvi in clinical trials. Hepatitis B virus screening and quantitative serum immunoglobulin screening are required before first dose.
- Pre-medicate with methylprednisolone (or an equivalent corticosteroid) and an antihistamine (e.g., diphenhydramine) prior to each infusion.
Briumvi must be diluted in 0.9% Sodium Chloride Injection, USP prior to administration
- First Infusion: 150 mg intravenous infusion
- Second Infusion: 450 mg intravenous infusion two weeks after the first infusion
- Subsequent Infusions: 450 mg intravenous infusion 24 weeks after the first infusion and every 24 weeks thereafter
Monitor patients closely during and for at least one hour after the completion of the first two infusions. Post-infusion monitoring of subsequent infusions is at physician discretion unless infusion reaction and/or hypersensitivity has been observed
Mechanism of Action
The precise mechanism by which ublituximab-xiiy exerts its therapeutic effects in multiple sclerosis is unknown, but is presumed to involve binding to 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.
The most common adverse reactions associated with the use of Briumvi include infusion reactions and upper respiratory tract infections.
Clinical Trial Results
The FDA approval of Briumvi was based on the ULTIMATE I & II randomized, double-blind, double-dummy, parallel group, active comparator-controlled clinical trials of identical design, in patients with RMS treated for 96 weeks. Patients were randomized to receive either Briumvi, given as an IV infusion of 150 mg administered in four hours, 450 mg two weeks after the first infusion administered in one hour, and 450 mg every 24 weeks administered in one hour, with oral placebo administered daily; or teriflunomide, the active comparator, given orally as a 14 mg daily dose with IV placebo administered on the same schedule as Briumvi . Both studies enrolled patients who had experienced at least one relapse in the previous year, two relapses in the previous two years, or had the presence of a T1 gadolinium (Gd)-enhancing lesion in the previous year. Patients were also required to have an Expanded Disability Status Scale (EDSS) score from 0 to 5.5 at baseline. The ULTIMATE I & II trials enrolled a total of 1,094 patients with RMS across 10 countries.
The primary endpoint of both trials was the Annualized Relapse Rate (ARR)
In ULTIMATE I, treatment with ublituximab resulted in an ARR of 0.08 (n=271), compared to 0.19 for teriflunomide (n=274).
In ULTIMATE II, treatment with ublituximab resulted in an ARR of 0.09 (n=272), compared to 0.18 for teriflunomide (n=272).
Briumvi also demonstrated superiority over teriflunomide in significantly reducing the number of T1 Gd-enhancing lesions and the number of new or enlarging T2 lesions