Briumvi (ublituximab) for multiple sclerosis

Last updated Feb. 18, 2025, by Marisa Wexler, MS
Fact-checked by Inês Martins, PhD

What is Briumvi for MS?

Briumvi (ublituximab-xiiy) is an infusion antibody-based therapy approved for adults with relapsing forms of multiple sclerosis (MS), from clinically isolated syndrome to relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS).

Developed by TG Therapeutics, the treatment is administered intravenously, or via infusions into the bloodstream. It has been proven in clinical trials to reduce relapses and brain lesions, and to slow disability progression.

Therapy snapshot

How does Briumvi work?

In MS, the body’s immune system mistakenly launches an attack that damages nerve cells in the brain and spinal cord. B-cells are a type of immune cell that play a central role in driving these autoimmune attacks.

Briumvi is a monoclonal antibody designed to target CD20, a protein found on the surface of B-cells. Its binding to CD20 is designed to reduce the number of B-cells in the body and lessen MS-driving inflammation.

The treatment works much like other anti-CD20 antibodies, but it has been glycoengineered — meaning that certain sugar molecules attached to the antibody have been altered — to increase its potency.

When antibodies like Briumvi bind to target proteins on cells, they can kill the cell through two main mechanisms: antibody-dependent cellular cytotoxicity, known as ADCC, or complement-dependent cytotoxicity, called CDC.

In ADCC, when the antibody binds to its target cell, it signals other immune cells to destroy that cell. In CDC, the antibody activates a group of immunological proteins, called the complement cascade, that kill the target cell. However, the complement system also participates in autoimmune processes, and its activation may result in side effects.

According to TG Therapeutics, Briumvi’s design makes it substantially more potent at triggering ADCC, and a less potent trigger of CDC, relative to other CD20 inhibitors used to treat MS.

Who can take Briumvi?

Briumvi was approved by the U.S. Food and Drug Administration in December 2022 for use in adults with relapsing forms of MS, including CIS, RRMS, and active SPMS.

In the European Union, the medication was approved in June 2023. It’s indicated in the EU for adults with relapsing forms of MS and active disease, as defined by certain clinical or imaging features.

Who should not use Briumvi?

Briumvi is not recommended for people with an active hepatitis B virus (HBV) infection. All patients should undergo hepatitis B screening before receiving their first dose.

The medication also should not be given to any patient who previously experienced a life-threatening infusion reaction to Briumvi.

How is Briumvi administered in MS?

Briumvi is given via intravenous infusions, or through a needle placed in a vein in the patient’s arm. Its administration should be done by an experienced healthcare provider.

Initially, Briumbi is administered in two infusions two weeks apart. The first contains 150 mg of the medication and is given over four hours, while the second is a 450 mg dose given in one hour. All subsequent doses, administered every six months thereafter, are given as hourlong 450 mg infusions.

About 30-60 minutes before each infusion, patients are premedicated with anti-inflammatory corticosteroids and antihistamines to reduce the frequency and severity of infusion reactions. An antifever medication also may be considered.

With the first two doses, patients should be observed for at least one hour after completing the infusion. For the following doses, monitoring may not be required, unless the patient experienced an infusion or allergic reactions with previous Briumvi infusions.

If a planned dose is missed, the medication should be administered as soon as possible, and the next infusion should be scheduled for six months after that.

Briumvi in ​​clinical trials

Briumvi’s approval was supported by data from two identical Phase 3 trials — ULTIMATE I (NCT03277261) and ULTIMATE II (NCT03277248) — that collectively enrolled nearly 1,100 patients with active, relapsing forms of MS. About 98% of participants had RRMS, and the rest had active SPMS.

ULTIMATE trials

Patients in the ULTIMATE trials were randomly assigned to receive treatment with either Briumvi in ​​the now-approved regimen — a 150 mg infusion on the first day of treatment, followed by a 450 mg infusion on day 15, then 450 mg infusions every six months — or with Aubagio (teriflunomide), an oral medication then already approved for MS. The trials ran for 96 weeks, or nearly two years.

Compared with Aubagio, Briumvi significantly reduced the annualized relapse rate, or the average number of relapses per year, by 59% in ULTIMATE I and 49% in ULTIMATE II, meeting the trials’ main goal. In both trials, relapse rates dropped from more than 0.175 relapses per year in the control group to fewer than 0.092 relapses per year with Briumvi.

It was the first MS treatment to push the annualized relapse rate below the 0.1 threshold in clinical trials, indicating less than one relapse per year.

Briumvi also lowered the number of lesions with active inflammation by 97% in both trials, and the number of new or enlarging lesions — those with and without active inflammation — by about 90%.

A similar number of patients on Aubagio and Briumvi experienced confirmed disability progression, as assessed by sustained increases in Expanded Disability Status Scale scores. However, in a pooled analysis, more patients on Briumvi experienced a confirmed disability improvement — meaning less severe disability — that lasted at least 12 weeks (12% vs. 6%) and 24 weeks (9.6% vs. 5.1%).

The rates of no evidence of disease activity, or NEDA-3 — a disease outcome defined as no relapses, no new MRI activity, and no confirmed disability worsening — were significantly higher for Briumvi. Indeed, participants receiving Briumvi were more than seven times as likely to achieve NEDA-3 over the 96-week trials than those on Aubagio.

Benefits of Briumvi were similar among key patient subgroups, outperforming Aubagio on efficacy measures when patients were grouped by sex, age, disability levels, relapse rates before treatment, treatment history, and lesion burden at the study’s start.

Participants who completed the ULTIMATE trials were eligible to enroll in an open-label extension (OLE) trial (NCT04130997), in which all received Briumvi for about three more years.

Data after three years in the OLE showed that Briumvi continued to reduce relapse rates over time in both groups. For those who started on Aubagio and switched to Briumvi in the extension trial, the annualized relapse rate was 0.045 after three years of Briumvi treatment. For those always on Briumvi for five years, the relapse rate was 0.020, indicating that patients experienced on average one relapse every 50 years.

By the end of the fifth year, a very small percentage of patients had experienced 24-week confirmed disability progression: 8% of those always on Briumvi and 14.3% of patients initially given Aubagio. This corresponded to a significant, 38.8% reduction in the risk of confirmed disability worsening in the Briumvi group.

Additionally, 17% of patients in the continuous group and 12.2% in the switch group experienced reduced disability lasting 24 weeks or more — meaning that disability reductions were 47.2% more likely with continuous Briumvi.

Common side effects of Briumvi

The most common side effects associated with Briumvi include infusion reactions and upper respiratory tract infections.

Infusion-related and allergic reactions

Treatment with Briumvi may cause infusion reactions such as fever, chills, headache, flu-like illness, rapid heart rate, nausea, throat irritation, or skin reddening. These typically occur within one day of dosing, and their incidence is highest with the first infusion.

If such reactions occur, they should be managed based on the particulars of the individual reaction. For less severe reactions, patients may temporarily stop the infusion, reduce the infusion rate, and/or use medications to ease their symptoms. For life-threatening reactions, however, use of Briumvi should be immediately and permanently stopped.

Low antibody levels and infections

Because Briumvi lowers the levels of B-cells, which normally work to produce antibodies that fight off infections, people using the treatment may experience low levels of circulating antibodies and be at a higher risk of serious infections.

In clinical trials, Briumvi most commonly resulted in infections in the respiratory and urinary tracts, and some patients also experienced a reactivation of the HBV virus, which can cause severe liver inflammation, liver failure, and death.

While progressive multifocal leukoencephalopathy or PML, a rare and serious brain infection, has not been reported in patients using Briumvi, it has been observed in individuals receiving treatment with other anti-CD20 antibodies. If signs of PML appear, patients should discontinue treatment and seek immediate medical care.

Antibody levels should be measured before starting Briumvi, and patients should be monitored for an active infection prior to every infusion. The treatment should be delayed in patients with an active infection. In such cases, the individual’s healthcare team may consider permanently stopping Briumvi if serious or recurrent infections occur, or if prolonged antibody depletion requires treatment.

Vaccines

Vaccination with live or live-attenuated vaccines is not recommended during treatment with Briumvi, and at least until a person’s B-cell levels have been restored.

Patients should receive all live or live-attenuated vaccines according to guidelines at least four weeks, or about one month, before starting Briumvi. Non-live vaccines should be given at least two weeks prior to starting treatment.

Babies who might have been exposed to Briumvi during pregnancy also should not receive vaccines containing a live or live-attenuated virus until their B-cell levels return to normal. Vaccines with non-live viruses may be administered, but babies should be assessed to determine whether a protective immune response was mounted.

Use in pregnancy and breastfeeding

Based on data from animal studies, Briumvi may cause harm to a developing fetus. Evidence has also shown that babies exposed to other CD20 inhibitors during pregnancy may have lower than normal levels of B-cells and other white blood cells.

Patients with the capacity to become pregnant should undergo pregnancy testing before each infusion and are advised to use contraception during treatment and for at least six months after stopping the therapy.

Any individuals who are breastfeeding or plan to breastfeed should inform their healthcare provider, as it is not clear if Briumvi can pass into breast milk, or whether it can have a negative effect on a nursing infant.

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