FDA Approves Briumvi for Relapsing Multiple Sclerosis

The FDA has approved ublituximab-xiiy (Briumvi; TG Therapeutics Inc) for the treatment of relapsing multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Ublituximab-xiiy is the first anti-CD20 monoclonal antibody approved for individuals with RMS that can be administered as a 1-hour intravenous (IV) infusion after the starting dose. The starting dose consists of 150 mg of ublituximab-xiiy administered in 4 hours, followed by an infusion of 450 mg administered in 1 hour on day 15. Afterward, the drug is administered in the 450-mg dosage in 1 hour every 24 weeks.

“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,” Lawrence Steinman, MD, professor of Neurology and Neurological Sciences and Pediatrics at Stanford University, said in a statement. “This approval is great news for patients living with MS and provides an appealing treatment alternative that can be administered in a 1-hour infusion twice-a-year following the starting dose, which I believe is an added benefit to patients.”.

ULTIMATE 1 (NCT03277261) and 2 (NCT03277248) are double-blinded, parallel-group, randomized clinical trials that have identical designs. The studies were intended to include individuals with RMS who were treated for 96 weeks.

They were randomized to receive either ublituximab-xii, as an infusion of 150 mg in 4 hours, then 450 mg in 1 hour 2 weeks after the first infusion, and then 450 mg every 24 weeks in 1 hour, or teriflunomide, an active comparator, which was given orally as a 14-mg daily dose with an intravenous placebo on the same schedule as ublituximab-xii.

Investigators enrolled individuals who had experienced at least 1 relapse in the previous year, 2 relapses in the previous 2 years, or had T1 gadolinium (Gd)-enhancing lesions that were present in the previous year. Further, individuals were also required to have an Expanded Disability Status Scale score between 0 and 5.5 at baseline.

The 2 trials had a total of 1094 individuals across 10 countries.

“The approval of [ublituximab-xii] is wonderful news. MS is most frequently diagnosed during the prime of a person’s life when they are just starting a career or beginning a family,” June Halper, MSN, APN-C, MSCN, FAAN, CEO of Consortium of Multiple Sclerosis Centers, said in the statement.

“The availability of anti-CD20s has launched a new era of high efficacy therapies for [MS],” she said.

Investigators found that annualized relapses in the ULTIMATE 1 trail were 0.076 for those on ublituximab-xii and 0.188 for those on teriflunomide. In ULTIMATE 3, they found 0.091 and 0.178, respectively.

The proportion of individuals with 12-week confirmed disability progression, calculated for both studies, was 5.2% for ublituximab-xii and 5.9% for teriflunomide.

Additionally, the mean number of T1 Gd-enhancing lesions per MRI were 0.016 for ublituximab-xii in ULTIMATE 1 and 0.491 for teriflunomide. For ULTIMATE 2, investigators found 0.009 and 0.250, respectively.

Reference

TG Therapeutics announces FDA approval of Briumvi (ublituximab-xiiy). TG Therapeutics. News release. December 28, 2022. Accessed January 5, 2023. https://ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-announces-fda-approval-briumvitm-ublituximab