Briumvi (ublituximab-xiiy) is an approved antibody-based therapy used to reduce relapses and slow the development of brain lesions in people with relapsing forms of multiple sclerosis (MS).
It is among the newest treatments for MS, having received approval in the U.S. at the end of 2022.
The therapy was developed by TG Therapeutics, which also has filed for ublituximab’s approval in the European Union.
In MS, the body’s immune system accidentally launches an inflammatory attack that damages healthy parts of the central nervous system. 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, such as Ocrevus (ocrelizumab) and Kesimpta (ofatumumab). However, 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 (ADCC), or complement-dependent cytotoxicity (CDC).
In ADCC, when the antibody binds to its target cell, it signals other immune cells to destroy the target cell. In CDC, the antibody activates a group of immunological proteins, called the complement cascade, which 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 anti-CD20 antibodies used for MS.
The U.S. Food and Drug Administration approved Briumvi in December 2022 for adults with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).
Briumvi is not recommended for people with an active hepatitis B virus infection. All patients should undergo hepatitis B screening prior to receiving their first dose.
People who previously experienced a life-threatening allergic reaction to Briumvi also should not be given the medication.
Briumvi is given via intravenous (into-the-vein) infusions. It is initially 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 hour-long 450 mg infusions.
Patients should be observed for at least one hour after completing the first two doses, and also may require monitoring following other doses if infusion or allergic reactions have occurred with Briumvi.
Before each infusion, patients are pre-medicated with anti-inflammatory corticosteroids and antihistamines to reduce the frequency and severity of infusion reactions. An anti-fever medication also may be considered.
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.
The safety and efficacy of Briumvi was assessed in a Phase 2 clinical trial (NCT02738775) sponsored by TG Therapeutics. The study involved 48 people with RRMS or active SPMS, and tested several doses of the therapy.
Briumvi overall was well-tolerated, with no serious side effects reported. Within four weeks, the median B-cell depletion was 99%, and all trial participants had at least 95% B-cell depletion, which was the trial’s main outcome.
The therapy was found to reduce relapse rates — from 1.45 to 0.07 relapses per year — and to completely eliminate signs of inflammatory brain lesions in patients. Also, 74% of trial participants had no evidence of disease activity when using a composite measure dubbed NEDA-3. That meant no relapses, no confirmed disability progression, and no new or enlarging lesions, at week 48 (11 months).
Briumvi’s approval was supported by data from two identical Phase 3 trials – ULTIMATE I (NCT03277261) and ULTIMATE II (NCT03277248) – that collectively enrolled 1,094 patients with active, relapsing forms of MS. About 98% of participants had RRMS, and the rest had active SPMS.
Patients in the ULTIMATE trials were randomly assigned to treatment with Briumvi in the approved regimen — a 150 mg infusion delivered over four hours on the first day of treatment, followed by a one-hour 450 mg infusion on day 15, then 450 mg infusions every six months — or with Aubagio (teriflunomide), an approved oral MS medication. The trials ran for 96 weeks, or nearly two years.
Compared with Aubagio, Briumvi significantly reduced the annualized relapse rate 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 0.92 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%).
Rates of NEDA-3 also were significantly higher for Briumvi, with participants being more than five times as likely to achieve NEDA-3 than those on Aubagio. Moreover, Briumvi was associated with better quality of life and higher rates of NEDA-4, which is similar to NEDA-3 but includes a fourth parameter related to brain shrinkage.
Benefits of Briumvi were similar among key patient subgroups, outperforming Aubagio on efficacy measures when patients were grouped by sex, age, disability, 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 ongoing open-label extension trial (NCT04130997), in which all are receiving Briumvi for up to 168 weeks, or a little over three years.
The most common side effects associated with Briumvi include:
Treatment with Briumvi may cause infusion-related 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.
Serious allergic reactions, including anaphylactic shock, have been reported in patients using Briumvi. The treatment should be immediately and permanently discontinued if a life-threatening or disabling reaction occurs.
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.
While progressive multifocal leukoencephalopathy (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.
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.
Based on data from animal studies, Briumvi may cause harm to a developing fetus. Patients with the capacity to become pregnant should undergo pregnancy testing before each infusion and are advised to use contraception while on this medication and for at least six months after stopping the therapy.
Patients who are breastfeeding or plan to breastfeed should inform their healthcare provider, as it is not clear if Briumvi can pass into breast milk.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
There are no known interactions between Briumvi and alcohol, but patients are advised to speak with their healthcare team about whether it is safe to drink while on the medication.
Briumvi was approved by the U.S. Food and Drug Administration in December 2022 for adults with relapsing forms of multiple sclerosis (MS). The approved indications include clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. The therapy also is under review in Europe.
According to animal studies, Briumvi may cause harm to a developing fetus and thus is not recommended for use during pregnancy. Patients who are able to become pregnant are advised to use effective contraceptive methods while on Briumvi and for at least six months after stopping treatment.
In clinical trials, the earliest signs of benefits were reported at six months, with the treatment inducing a rapid and marked depletion of B-cells within two weeks after the first dose. However, each person may react differently to medications, and patients are advised to discuss with their healthcare team how Briumvi may help in their particular case.
Neither hair loss nor weight gain have been reported as a side effect of Briumvi. Other anti-CD20 therapies also generally do not cause these side effects. Patients who experience unanticipated effects after starting a new multiple sclerosis therapy are advised to talk to their healthcare provider.
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