Briumvi: Uses, Dosage & Side Effects

What Is Briumvi and What Is It Used For?

Briumvi contains the active substance ublituximab, a chimeric monoclonal antibody produced using recombinant DNA technology. As a monoclonal antibody, ublituximab is a type of highly specialized protein that has been engineered to recognize and bind to one specific molecular target on cells in the body. In the case of Briumvi, that target is CD20, a transmembrane phosphoprotein expressed on the surface of pre-B lymphocytes and mature B lymphocytes. CD20 is not expressed on lymphoid stem cells or plasma cells, which is important because it means that B-cell depletion does not completely eliminate the ability to produce antibodies.

Multiple sclerosis is a chronic, immune-mediated inflammatory disease of the central nervous system (CNS) characterized by demyelination, axonal damage, and progressive neurodegeneration. For decades, T lymphocytes were considered the primary drivers of MS pathology. However, over the past two decades, compelling evidence has emerged demonstrating that B lymphocytes play a critical and multifaceted role in the disease. B cells contribute to MS pathogenesis through several mechanisms: they act as antigen-presenting cells that activate pathogenic T cells, they produce pro-inflammatory cytokines (such as interleukin-6, tumor necrosis factor-alpha, and lymphotoxin-alpha), and they can form ectopic lymphoid follicles in the meninges that sustain chronic inflammation. B cells also produce antibodies, and while the exact role of antibodies in MS remains debated, oligoclonal bands (antibodies found in cerebrospinal fluid but not in serum) remain one of the most consistent diagnostic biomarkers of the disease.

Ublituximab has been glycoengineered to have a low-fucose content in its Fc region, which enhances its binding affinity to the Fc gamma receptor IIIa (FcgammaRIIIa, also known as CD16a) on natural killer cells and other immune effector cells. This glycoengineering results in significantly enhanced antibody-dependent cellular cytotoxicity (ADCC) compared with non-glycoengineered anti-CD20 antibodies. ADCC is the primary mechanism by which ublituximab depletes CD20-positive B cells: natural killer cells recognize the antibody-coated B cells and release cytotoxic granules that destroy them. Ublituximab also induces B-cell depletion through complement-dependent cytotoxicity (CDC) and direct apoptosis, though these are secondary mechanisms.

The unique epitope targeted by ublituximab on CD20 overlaps with but is distinct from the epitopes recognized by other anti-CD20 antibodies such as rituximab and ocrelizumab. This, combined with the enhanced ADCC activity from glycoengineering, allows ublituximab to achieve rapid and deep B-cell depletion. In clinical studies, near-complete depletion of circulating CD20-positive B cells was observed within two weeks of the initial dose in most patients.

Briumvi is indicated for the treatment of relapsing forms of multiple sclerosis in adults. This includes clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis (SPMS). The efficacy and safety of Briumvi were established in two pivotal phase III clinical trials:

• ULTIMATE I: A randomized, double-blind, double-dummy, active-controlled trial comparing ublituximab with teriflunomide (14 mg daily) in 549 patients with relapsing MS. Over 96 weeks, patients treated with ublituximab had an annualized relapse rate (ARR) of 0.076 compared with 0.188 for teriflunomide, representing a 59% reduction (p < 0.005). Ublituximab also showed superior results on MRI endpoints, including a 97% reduction in T1 gadolinium-enhancing lesions and a 92% reduction in new or enlarging T2 lesions.
• ULTIMATE II: A similarly designed trial in 545 patients demonstrated consistent results, with an ARR of 0.091 for ublituximab versus 0.178 for teriflunomide, representing a 49% reduction (p < 0.005). MRI outcomes were similarly favorable, with substantial reductions in both enhancing and new T2 lesions.

In pooled analyses of both trials, ublituximab also showed a trend toward reducing confirmed disability progression, although the individual trials were not powered to demonstrate statistical significance on disability endpoints. The onset of efficacy was rapid, with significant reductions in MRI lesion activity observed as early as the first post-baseline MRI assessment. Briumvi was first approved by the U.S. Food and Drug Administration (FDA) in December 2022 and subsequently by the European Medicines Agency (EMA) in 2023.

What Should You Know Before Taking Briumvi?

Before initiating treatment with Briumvi, your healthcare provider will conduct a thorough medical evaluation to ensure the medication is appropriate for you. This evaluation is essential because Briumvi works by depleting B lymphocytes, which are a critical component of the immune system. While this mechanism is what makes Briumvi effective against MS, it also means that certain pre-existing conditions or situations may increase the risk of complications. Understanding these factors will help you and your doctor make an informed decision about your treatment.

Contraindications

Briumvi should not be used in the following situations:

• Active hepatitis B virus (HBV) infection: Patients with active HBV must not receive Briumvi, as anti-CD20 therapy can cause HBV reactivation, potentially leading to fulminant hepatitis, hepatic failure, and death. All patients must be screened for HBV before starting treatment.
• Known severe hypersensitivity: Patients who have experienced a life-threatening infusion reaction to ublituximab should not receive further infusions. Milder infusion-related reactions can typically be managed with dose modifications and pre-medication.
• Active severe infections: Treatment should be delayed in patients with an active, severe infection until the infection is fully resolved. Starting immunosuppressive therapy during active infection can lead to worsening of the infection.

Warnings and Precautions

Several important safety considerations should be discussed with your healthcare provider before and during treatment with Briumvi:

• Infusion-related reactions (IRRs): IRRs are the most common adverse events with Briumvi, occurring in approximately 40-50% of patients with the first infusion. Symptoms may include headache, nausea, fever, chills, fatigue, dizziness, throat irritation, shortness of breath, and pruritus. Pre-medication with a corticosteroid (e.g., methylprednisolone 100 mg IV), an antihistamine (e.g., diphenhydramine), and an antipyretic (e.g., acetaminophen) is required before each infusion to reduce the risk and severity of IRRs.
• Infections: Briumvi increases the risk of upper respiratory tract infections, urinary tract infections, and potentially other infections. Patients should be monitored for signs and symptoms of infection during and after treatment. Serious infections, including opportunistic infections, have been reported with anti-CD20 therapies.
• Progressive multifocal leukoencephalopathy (PML): PML is a rare but serious brain infection caused by the JC virus that has been reported with anti-CD20 antibodies and other MS therapies. Symptoms may include progressive weakness, clumsiness, vision changes, confusion, and personality changes. Patients should be monitored for any new or worsening neurological symptoms.
• Hepatitis B reactivation: Even in patients with resolved HBV (HBsAg negative, anti-HBc positive), reactivation can occur during anti-CD20 therapy. Monitoring of HBV DNA and liver function is recommended during and after treatment.
• Reduced immunoglobulin levels: Prolonged treatment with anti-CD20 antibodies can lead to decreased immunoglobulin levels, particularly IgM and IgG. Immunoglobulin levels should be monitored before and during treatment. Significantly low levels may increase infection risk and may require treatment modification.
• Vaccinations: All recommended vaccinations should be completed at least 4 weeks before initiating Briumvi for non-live vaccines and at least 6 weeks before for live or live-attenuated vaccines. Live vaccines should not be administered during treatment or until B-cell recovery. The immune response to vaccines may be attenuated during treatment.

Pregnancy and Breastfeeding

Briumvi should generally be avoided during pregnancy unless the potential benefit to the mother justifies the potential risk to the fetus. Ublituximab is an IgG1 antibody and is expected to cross the placental barrier, particularly during the second and third trimesters. Monoclonal antibodies that deplete B cells are known to cause transient B-cell depletion and lymphopenia in neonates born to mothers treated during pregnancy. Infants born to mothers treated with Briumvi should be monitored for B-cell depletion, and vaccination with live or live-attenuated vaccines should be deferred until the infant's B-cell counts have recovered.

Women of childbearing potential should use effective contraception during treatment and for at least 6 months after the last infusion of Briumvi. It is not known whether ublituximab is excreted in human breast milk, but human IgG is known to be present in breast milk. The decision to breastfeed during treatment should be made in consultation with a healthcare provider, weighing the benefits of breastfeeding against the potential risks to the infant.

How Does Briumvi Interact with Other Drugs?

Because ublituximab is a monoclonal antibody, it is eliminated through catabolism (breakdown into amino acids) rather than through hepatic metabolism by cytochrome P450 (CYP) enzymes. This means that traditional pharmacokinetic drug-drug interactions, which commonly affect small-molecule drugs, are not expected with Briumvi. In clinical trials, no formal drug interaction studies were required or conducted based on the established pharmacological characteristics of monoclonal antibodies.

However, pharmacodynamic interactions are an important consideration. Because Briumvi causes prolonged B-cell depletion and modifies immune function, combining it with other immunomodulatory or immunosuppressive agents can result in additive immunosuppression, increasing the risk of infections and other immune-related complications. When switching from other MS disease-modifying therapies to Briumvi, or when using Briumvi in combination with other treatments, the duration and mechanism of action of the prior therapy must be considered.

Switching from Other MS Therapies

When transitioning from another disease-modifying therapy to Briumvi, the mechanism of action and duration of effect of the prior therapy must be carefully considered. For oral therapies such as dimethyl fumarate or teriflunomide, a washout period of approximately 2-4 weeks is generally sufficient. For S1P receptor modulators (fingolimod, siponimod, ozanimod), lymphocyte counts should be monitored and allowed to recover before initiating Briumvi, which typically takes 1-2 months after discontinuation. For natalizumab, a minimum 6-week washout is recommended, with consideration of PML risk. For therapies with prolonged immune effects such as alemtuzumab or cladribine, extended monitoring of immune cell recovery is essential before starting Briumvi.

What Is the Correct Dosage of Briumvi?

Briumvi is administered exclusively by intravenous infusion in a healthcare setting where appropriate medical support is available to manage potential infusion-related reactions. The dosing regimen has been designed to balance rapid B-cell depletion with manageable tolerability, particularly with regard to infusion-related reactions. The split initial dose helps reduce the severity of IRRs that are most common with the first exposure to the medication.

Adults

Children

The safety and efficacy of Briumvi have not been established in pediatric patients under 18 years of age. Currently, Briumvi is not approved for use in children and adolescents. Clinical trials in the pediatric population have not been completed, and no dosing recommendations can be made for this age group. If a child or adolescent has relapsing MS, other approved disease-modifying therapies should be considered in consultation with a pediatric neurologist.

Elderly

Limited clinical data are available for patients aged 65 years and older, as clinical trials included relatively few patients in this age group. No dose adjustment is recommended based on age alone. However, elderly patients may be at higher risk for infections due to age-related changes in immune function, and this should be considered when making treatment decisions. Close monitoring of infection signs and immunoglobulin levels is particularly important in older patients receiving Briumvi.

Missed Dose

If a scheduled Briumvi infusion is missed or needs to be delayed, it should be administered as soon as possible. There is no need to restart the dosing regimen or administer a loading dose. The next infusion should then be scheduled 24 weeks from the date of the administered infusion. If a significant delay occurs (several months), your healthcare provider may check B-cell levels and immunoglobulin levels before proceeding with the next infusion to ensure it remains appropriate.

Overdose

There is limited experience with overdose of Briumvi. In the event of an overdose, the infusion should be immediately interrupted, and the patient should be closely monitored for infusion-related reactions and other adverse effects. Given the mechanism of action, an overdose would be expected to cause more profound and prolonged B-cell depletion. There is no specific antidote for ublituximab. Treatment is supportive and symptomatic, with monitoring of B-cell counts and immunoglobulin levels over the following months.

What Are the Side Effects of Briumvi?

Like all medications, Briumvi can cause side effects, although not everybody will experience them. The safety profile of Briumvi has been characterized in the ULTIMATE I and ULTIMATE II pivotal clinical trials, which collectively enrolled over 1,000 patients with relapsing MS treated with ublituximab. The most frequently reported adverse events were infusion-related reactions, which are a known class effect of anti-CD20 monoclonal antibodies. The overall safety profile of Briumvi is generally consistent with other anti-CD20 therapies used in MS.

Understanding the frequency and nature of side effects can help you recognize them early and communicate effectively with your healthcare team. Side effects are classified by frequency according to the following standard medical convention:

Infusion-related reactions are the hallmark side effect of Briumvi and anti-CD20 therapies in general. In the ULTIMATE trials, approximately 47% of patients experienced an IRR with the first infusion (Day 1), but the incidence dropped to approximately 5% with the Day 15 infusion and continued to decrease with subsequent infusions. The vast majority of IRRs were mild to moderate (Grade 1-2) and were effectively managed by temporarily slowing or pausing the infusion and administering symptomatic treatment. Fewer than 1% of patients discontinued treatment due to IRRs.

The pattern of infections observed with Briumvi is consistent with what is known about B-cell depleting therapies. While the overall rate of infections was similar between the ublituximab and teriflunomide groups in clinical trials, the types of infections may differ. Upper respiratory tract infections were the most common infectious adverse event. Serious infections occurred at a low rate (approximately 3-5% of patients) and were manageable with standard treatment.

Long-term treatment with anti-CD20 antibodies can lead to progressive decreases in immunoglobulin levels, particularly IgM and, to a lesser extent, IgG. In the ULTIMATE trials, decreases in IgM below the lower limit of normal were observed in approximately 15% of patients after 96 weeks. While most patients remained clinically well despite reduced immunoglobulin levels, significantly low IgG levels may increase susceptibility to infections and should prompt discussion about potential treatment modifications.

How Should You Store Briumvi?

Briumvi is supplied as a concentrated solution for intravenous infusion in single-dose vials. Because Briumvi is administered in a healthcare setting, storage is typically managed by the pharmacy or infusion center. However, understanding storage requirements can be helpful for patients and caregivers who may need to transport or temporarily store the medication.

The undiluted Briumvi vials should be stored in a refrigerator at 2–8°C (36–46°F). The vials must be kept in the original carton to protect from light. Briumvi must not be frozen. If a vial has been accidentally frozen, it must be discarded and not used. The vials should also not be shaken vigorously, as this can damage the protein structure of the monoclonal antibody.

Once diluted for infusion, the Briumvi solution should be used promptly. If not used immediately, the diluted solution can be stored at room temperature (20–25°C / 68–77°F) for up to 8 hours, or in a refrigerator (2–8°C) for up to 24 hours. These storage times include the duration of the infusion itself. The diluted solution should be inspected visually for particulate matter and discoloration prior to administration. If particles or discoloration are observed, the solution should not be used.

As with all medications, Briumvi should be kept out of the reach and sight of children. Do not use the medication after the expiry date stated on the vial label and carton. Any unused product or waste material should be disposed of in accordance with local requirements for pharmaceutical waste.

What Does Briumvi Contain?

Understanding the composition of Briumvi is important, particularly if you have known allergies or sensitivities to any pharmaceutical ingredients. The active and inactive ingredients of Briumvi are listed below:

Active ingredient: Ublituximab 150 mg per 6 mL (25 mg/mL). Ublituximab is a chimeric, glycoengineered IgG1 monoclonal antibody directed against the CD20 antigen on B lymphocytes. It is produced using recombinant DNA technology in a mammalian cell expression system (Chinese hamster ovary cells) and is specifically engineered to have a low-fucose glycan profile in its Fc region, which enhances antibody-dependent cellular cytotoxicity.

Inactive ingredients (excipients):

• Sodium chloride: An isotonicity agent that ensures the solution has the appropriate osmolality for intravenous administration.
• Sodium citrate dihydrate: A buffering agent that maintains the pH of the solution within the optimal range for protein stability (approximately pH 6.0).
• Citric acid monohydrate: A co-buffering agent that works with sodium citrate to maintain solution pH.
• Polysorbate 80: A non-ionic surfactant that prevents aggregation and adsorption of the monoclonal antibody to surfaces.
• Water for injection: The vehicle for the solution, meeting pharmaceutical-grade purity requirements.

Briumvi does not contain preservatives. Each vial is for single use only. The solution is clear to slightly opalescent, colorless to slightly yellow. The product does not contain latex in the vial stopper or any components derived from animal sources other than the mammalian cell line used for production. Patients with known hypersensitivity to any of the excipients listed above should inform their healthcare provider before receiving treatment.