Ublituximab

Ublituximab (brand name Briumvi) is used to treat relapsing forms of multiple sclerosis (MS) in adults. It belongs to a class of drugs called CD20 monoclonal antibodies and works by targeting and depleting B cells. These are immune cells that drive the inflammatory process responsible for nerve damage in MS. Ublituximab is given as an intravenous (IV) infusion every 6 months by a healthcare provider, after an initial loading series.

Ublituximab received FDA approval on December 28, 2022, under the brand name Briumvi. The full biological name is ublituximab-xiiy. There is currently no generic version (known as a biosimilar) available.

Ublituximab infusion is used to treat relapsing forms of multiple sclerosis (MS) in adults, including:

• Clinically isolated syndrome: a first episode of neurological symptoms that may indicate MS
• Relapsing-remitting MS: a course of disease where symptoms flare up from time to time, then partially or fully recover
• Active secondary progressive MS: a later stage of MS where relapses continue to occur alongside gradual worsening.

Clinical trials (ULTIMATE I and II) showed that ublituximab significantly outperformed teriflunomide (Aubagio) at reducing relapses and suppressing new brain lesions on MRI:

• 49% to 59% fewer relapses with ublituximab compared to teriflunomide across two studies
• 97% suppression of T1 gadolinium-enhancing (Gd+) brain lesions on MRI over 2 years in both studies
• 86% to 87% of people taking ublituximab had zero relapses during the trials.

The precise mechanism of ublituximab is not completely understood, but it is thought to involve binding to a protein called CD20 on the surface of B lymphocytes. These are white blood cells that play a central role in the immune response. In MS, B cells contribute to the inflammation that damages the myelin sheath, the protective coating that surrounds nerve fibres and allows them to transmit signals efficiently. When this coating is damaged, it disrupts communication between the brain and the rest of the body, causing MS symptoms.

By binding to CD20, ublituximab destroys these B cells through a process called antibody-dependent cellular cytolysis and complement-dependent cytolysis, reducing their levels for several months after each infusion. This helps to slow the inflammatory damage to the myelin sheath and reduce MS relapses and new brain lesions.

Ublituximab belongs to the drug class called CD20 monoclonal antibodies, which also includes ocrelizumab (Ocrevus) and ofatumumab (Kesimpta).

• Ublituximab is given through a needle placed in your vein (intravenous infusion) in your arm.
• Before treatment with ublituximab, you will receive a corticosteroid and an antihistamine medicine to help reduce the risk of infusion reactions by making them less frequent and less severe. You may also receive other medicines to help reduce the risk of an infusion reaction (see Important information above).
• Your first dose of ublituximab will last about 4 hours.
• Your second dose of ublituximab will be given 2 weeks after your first dose. This infusion will last about 1 hour.
• Your next doses of ublituximab will be given as 1 infusion every 24 weeks. These infusions will last about 1 hour.

See the Briumvi (ublituximab) Prescribing Information for more detailed information.

Do not receive ublituximab if you:

• have an active hepatitis B virus (HBV) infection.
• have had a life-threatening allergic reaction to ublituximab, ublituximab, or any of the inactive ingredients in the infusion (see the ingredients list below). Tell your healthcare provider if you have had an allergic reaction to ublituximab.

Before receiving ublituximab, 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 ublituximab. You should not receive ‘live’ or ‘live-attenuated’ vaccines while you are being treated with ublituximab 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 ublituximab. If you would like to receive any non-live vaccines while you are being treated with ublituximab, talk to your healthcare provider. If you have a baby and you received ublituximab during your pregnancy, it is important to tell your baby’s healthcare provider about receiving ublituximab 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 ublituximab will harm your unborn baby. Use effective birth control during treatment with ublituximab 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 ublituximab during pregnancy. If you become pregnant while receiving ublituximab, or within 6 months of your last dose, tell your healthcare provider right away. You or your healthcare provider can enrol in the ublituximab 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 ublituximab passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take ublituximab.

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

Important information and potentially serious side effects

Ublituximab can potentially cause serious side effects, including:

• Infusion reactions. These are one of the most common side effects of ublituximab 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 up to 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 ublituximab. Ublituximab 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 ublituximab until your infection is gone. Hepatitis B virus (HBV) reactivation. Before starting treatment with ublituximab, your healthcare provider will do blood tests to check for hepatitis B viral infection. If you have ever had a hepatitis B virus infection, the virus may become active again during or after treatment with ublituximab. 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 ublituximab. Weakened immune system. Ublituximab 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 ublituximab. 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. Ublituximab may cause a decrease in some types of antibodies. Your healthcare provider will do blood tests to check your immunoglobulin levels.
• Liver damage. Ublituximab may cause liver damage. Your healthcare provider will do blood tests to check your liver before you start ublituximab 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 ublituximab 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.

Adult dose of ublituximab for multiple sclerosis

• First Infusion: 150 mg intravenous infusion
• Second Infusion: 450 mg intravenous infusion two weeks after the first infusion
• Subsequent Infusions: 450 mg intravenous infusion 24 weeks after the first infusion and every 24 weeks thereafter.

Must be diluted in 0.9% Sodium Chloride Injection, USP before administration.

You will be monitored closely during and for at least one hour after the completion of the first two infusions. Post-infusion monitoring of subsequent infusions is at your healthcare provider's discretion unless infusion reactionand/or hypersensitivity have been observed

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.

Avoid receiving a "live" vaccine while you are being treated with ublituximab, and for at least 4 weeks before your treatment. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), and zoster (shingles).

Avoid receiving a "non-live" vaccine for at least 2 weeks before your treatment with ublituximab.

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

TG Therapeutics, Inc., manufactures ublituximab under the brand name Briumvi.