Briumvi

Briumvi (ublituximab) is used to treat relapsing forms of multiple sclerosis (MS) in adults. Briumvi (ublituximab-xiiy) is a prescription treatment given by intravenous (IV) infusion every 24 weeks, or about twice a year, by a healthcare provider. After two starting infusions, each maintenance infusion takes about 1 hour.

Briumvi is a chimeric monoclonal IgG1 antibody that targets CD20, a protein on the surface of B cells, a type of white blood cell involved in the immune response that damages the nervous system in MS. The precise way Briumvi works in MS is not known, but it is thought to bind to CD20 on pre-B cells and mature B cells, destroying them through antibody-dependent cellular cytolysis and complement-dependent cytolysis. Reducing B-cell activity is thought to slow the inflammatory process that damages the myelin sheath, the protective covering around nerves, and causes MS relapses and brain lesions. Briumvi is glycoengineered to have a reduced fucose content, which is designed to make B-cell killing more efficient at a lower dose. Briumvi belongs to the drug class called CD20 monoclonal antibodies.

Briumvi (ublituximab-xiiy) gained FDA approval on December 28, 2022. FDA approval of Briumvi was supported by two phase 3, randomized, double-blind, double-dummy, active comparator-controlled trials: ULTIMATE I (NCT03277261) and ULTIMATE II (NCT03277248) in 1,094 adults with relapsing MS. Both trials compared Briumvi to teriflunomide over 96 weeks. Briumvi reduced annualized relapse rates by 59% and 49%, respectively, and reduced T1 gadolinium-enhancing brain lesions by 97% in both studies.

There is no Briumvi (ublituximab) biosimilar.

Briumvi is FDA-approved to treat relapsing forms of multiple sclerosis in adults, including:

• Clinically isolated syndrome (CIS)
• Relapsing-remitting MS (RRMS)
• Active secondary progressive MS (SPMS).

Briumvi was studied in two identical 96-week trials, ULTIMATE I (Study 1) and ULTIMATE II (Study 2), in 1,094 adults with relapsing MS. Both trials compared Briumvi with teriflunomide 14 mg taken by mouth once daily. Everyone taking part had had at least one relapse in the previous year, two relapses in the previous two years, or an active brain lesion on MRI in the previous year.

A relapse rate of 0.076 per year means that, on average, patients had about one relapse every 13 years of treatment. Briumvi did not slow the worsening of disability more than teriflunomide did in these trials.

• Briumvi is given through a needle placed in your vein (intravenous infusion) in your arm.
• Before every Briumvi infusion you will be given a corticosteroid, usually 100 mg of methylprednisolone into a vein or an equivalent corticosteroid, about 30 minutes beforehand, and an antihistamine such as diphenhydramine about 30 to 60 minutes beforehand. These reduce how often infusion reactions happen and how severe they are. A fever and pain reliever such as acetaminophen may also be considered.
• Your first dose of Briumvi will last about 4 hours.
• Your second dose of Briumvi will be given 2 weeks after your first dose. This infusion will last about 1 hour.
• Your next doses of Briumvi will be given as 1 infusion every 24 weeks. These infusions will last about 1 hour.

See the Briumvi Prescribing Information for more detailed information.

Do not receive Briumvi if you:

• have an active hepatitis B virus (HBV) infection
• have had a life-threatening allergic reaction to Briumvi. Tell your healthcare provider if you have had an allergic reaction to Briumvi.

Before receiving Briumvi, tell your healthcare provider about all your medical conditions, including if you:

• have or think you have an infection
• take or plan to take medicines that affect your immune system. These medicines may increase your risk of getting an infection
• have ever had hepatitis B or are a carrier of the hepatitis B virus
• have a history of liver problems
• have had a recent vaccination or are scheduled to receive any vaccinations. You should receive any required ‘live’ or ‘live-attenuated’ vaccines at least 4 weeks before you start treatment with Briumvi. You should not receive ‘live’ or ‘live-attenuated’ vaccines while you are being treated with Briumvi and until your healthcare provider tells you that your immune system is no longer weakened. When possible, you should receive any ‘non-live’ vaccines at least 2 weeks before you start treatment with Briumvi. If you would like to receive any non-live vaccines while you are being treated with Briumvi, talk to your healthcare provider. If you have a baby and you received Briumvi during your pregnancy, it is important to tell your baby’s healthcare provider about receiving Briumvi so they can decide when your baby should be vaccinated.
• are pregnant, think that you might be pregnant, or plan to become pregnant. It is not known if Briumvi will harm your unborn baby. Use effective birth control during treatment with Briumvi and for at least 6 months after your last infusion. Talk with your healthcare provider about the right birth control method for you during this time.

Pregnancy registry. There is a pregnancy registry for women who take Briumvi during pregnancy. If you become pregnant while receiving Briumvi, or within 6 months of your last dose, tell your healthcare provider right away. You or your healthcare provider can enrol in the Briumvi Pregnancy Registry by calling 1-877-411-4546 or visiting www.briumvipregnancyregistry.com. The registry collects information about your health and your baby's health during and after treatment.

• are breastfeeding, or plan to breastfeed. It is not known if Briumvi passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Briumvi.

It is not known if Briumvi is safe or effective in children.

Tests you will have before and during Briumvi treatment

Before your first Briumvi infusion your healthcare provider will:

• screen you for hepatitis B virus infection. Briumvi must not be given if you have an active hepatitis B infection. If you have had hepatitis B in the past or carry the virus, a liver disease specialist should be consulted before and during treatment.
• measure your quantitative serum immunoglobulin levels. If these are low, an immunology specialist should be consulted before you start.
• check your liver with blood tests measuring ALT, AST, alkaline phosphatase, and bilirubin.
• check that your vaccinations are up to date. Live or live-attenuated vaccines must be given at least 4 weeks before you start, and non-live vaccines at least 2 weeks before where possible.

Before every infusion your healthcare provider will check whether you have an active infection. If you do, your infusion will be delayed until it clears.

During treatment your immunoglobulin levels are monitored, and liver blood tests are repeated if your provider thinks they are needed.

Important information and potentially serious side effects

Briumvi can potentially cause serious side effects, including:

• Infusion reactions. These are one of the most common side effects of Briumvi and can be serious, sometimes requiring hospitalization. You will be monitored during your infusion and may be monitored after each infusion for signs and symptoms of an infusion reaction. Tell your healthcare provider if you get any of these symptoms: Fever Itchy skin Wheezing Chills Dizziness Nausea Headache Feeling faint Abdominal pain Flu-like symptoms Swelling of the tongue or throat Throat irritation Fast heartbeat Trouble breathing Redness of the face or skin Hives

Infusion reactions can happen over 24 hours after your infusion. Call your healthcare provider right away if you get any of the signs or symptoms listed above. If you get an infusion reaction, your healthcare provider may need to stop or slow down the rate of your infusion.

• Infections. Infections, including upper respiratory tract infections, are a common side effect of Briumvi. Briumvi increases your risk of getting infections caused by bacteria or viruses that may be life-threatening. Tell your healthcare provider if you have an infection or any of the following signs of infection: fever, chills, a cough that does not go away, or painful urination. Your healthcare provider should delay your treatment with Briumvi until your infection is gone. Hepatitis B virus (HBV) reactivation. Before starting treatment with Briumvi, your healthcare provider will do blood tests to check for hepatitis B viral infection. If you have ever had hepatitis B virus infection, the virus may become active again during or after treatment with Briumvi. Reactivation may cause serious liver problems, including liver failure or death. Your healthcare provider will monitor you if you are at risk for HBV reactivation during treatment and after you stop receiving Briumvi. Weakened immune system. Briumvi taken before or after other medicines that weaken the immune system could increase your risk of getting infections. Progressive multifocal leukoencephalopathy (PML). PML has been reported with Briumvi. PML is a rare, serious brain infection caused by a virus that may worsen over days or weeks and can result in death or severe disability. Tell your healthcare provider right away if you have any new or worsening neurological signs or symptoms, including weakness on one side of your body, loss of coordination, vision problems, or changes in thinking, memory, or personality.
• Low immunoglobulins. Briumvi may cause a decrease in some types of antibodies. Your healthcare provider will do blood tests to check your immunoglobulin levels.
• Liver damage. Briumvi may cause liver damage. Your healthcare provider will do blood tests to check your liver before you start Briumvi and while you are receiving this medicine if needed. Tell your healthcare provider right away if you have any symptoms of liver damage, such as: yellowing of the skin and eyes (jaundice) nausea vomiting unusual darkening of the urine feeling tired or weak.

Common side effects

The most common side effects of Briumvi are infusion reactions, upper and lower respiratory tract infections, herpes infections, extremity pain, insomnia, and fatigue.

Notes

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How common are Briumvi side effects?

The figures below come from the two ULTIMATE trials, in which 545 adults received Briumvi and 548 received teriflunomide. They show side effects reported by at least 5 in every 100 people taking Briumvi and more often than with teriflunomide.

Other findings from the same trials:

• Infusion reactions were most common with the first infusion (43%), falling to 10% with the second infusion and 8% with the third. Three people (0.6%) had a serious infusion reaction. There were no fatal infusion reactions.
• Infections of any kind occurred in 56% of people taking Briumvi and 54% taking teriflunomide. Serious infections occurred in 5% compared with 3%. Urinary tract infection occurred in 10%.
• Three deaths from infection occurred in people treated with Briumvi in controlled trials, caused by post-measles encephalitis, pneumonia, and infection after surgery for an ectopic pregnancy.
• Infection was the most common reason for stopping Briumvi (1.3% of people).
• Immunoglobulin M (IgM) levels fell below the lower limit of normal in 20.9% of people by 96 weeks. IgG fell below normal in 6.5% and IgA in 2.4%.
• Neutrophil counts fell below normal in 15% of people taking Briumvi, compared with 22% taking teriflunomide.

Liver injury and progressive multifocal leukoencephalopathy (PML) have been reported since Briumvi was approved. Because these are reported voluntarily, how often they happen is not known.

Adult dose of Briumvi for multiple sclerosis

• First infusion: 150 mg by intravenous infusion, given over about 4 hours
• Second infusion: 450 mg by intravenous infusion two weeks after the first infusion, given over about 1 hour
• Subsequent infusions: 450 mg by intravenous infusion 24 weeks after the first infusion and every 24 weeks thereafter, each given over about 1 hour

Briumvi must be diluted in 0.9% Sodium Chloride Injection, USP before administration and given through a dedicated line.

You will be monitored during each infusion and for at least one hour after the first two infusions are finished. Monitoring after later infusions is at your healthcare provider's discretion, unless you have had an infusion reaction or hypersensitivity reaction with the current or any earlier infusion.

If you miss a scheduled Briumvi infusion, contact your healthcare provider so it can be given as soon as possible. Do not wait until your next scheduled infusion. Once the missed infusion has been given, your schedule is reset and your next infusion is given 24 weeks later. Briumvi infusions must always be separated by at least 5 months.

Briumvi has an average terminal half-life of 22 days, which means it takes about 22 days for the amount in your body to fall by half. Most of the drug has cleared within a few months of your last infusion.

The effect on your B cells lasts much longer than the drug itself. Briumvi starts reducing B-cell counts within 24 hours of the first infusion. After the last infusion, it took a median of 70.3 weeks, or about 16 months, for B-cell counts to return to normal or to their starting level. Within 18 months of the last infusion, B-cell counts had recovered in 58% of people. This is why vaccination advice and infection precautions continue after you stop treatment.

• Children: Briumvi has not been shown to be safe or effective in children.
• Adults aged 65 and over: the clinical trials did not include enough people aged 65 or older to know whether they respond differently.
• Kidney or liver problems: mild kidney or liver impairment does not meaningfully change how Briumvi behaves in the body. The effect of moderate to severe kidney or liver impairment is not known.
• Antibodies to the drug: in the clinical trials, 81% of people treated with Briumvi developed antibodies to it at some point and 6.4% developed neutralizing antibodies. These antibodies had no observable effect on how well Briumvi worked or on side effects.

Tell your doctor about all your other medicines, especially:

• Drugs that weaken the immune system, such as cancer medications, steroids, and medicines to prevent organ transplant rejection
• Vaccines that you have recently received or are scheduled to receive.

This list is not complete. Other drugs may interact with ublituximab, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Briumvi is stored and prepared by your healthcare provider, not at home. Vials are kept in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect them from light. Vials must not be frozen or shaken.

Once diluted ready for infusion, the solution should be used straight away. If it is not, it can be kept in a refrigerator for up to 24 hours, then for up to a further 8 hours at room temperature up to 25°C (77°F), which includes the time it takes to warm up and the infusion itself.

Active ingredient: ublituximab-xiiyInactive ingredients: hydrochloric acid, polysorbate 80, sodium chloride, sodium citrate, Water for Injection, USP.