Zilbrysq

Zilbrysq (zilucoplan) is a prescription once-daily injection used to treat generalized myasthenia gravis (gMG) in adults who are AChR antibody positive (AChR-Ab+). Zilbrysq is a complement C5 inhibitor that blocks the C5 protein in the immune system. You can inject it yourself under the skin (subcutaneous injection) using an autoinjector or a prefilled syringe.

As a complement C5 inhibitor, Zilbrysq works by binding to a protein called complement component 5 (C5) to prevent immune-mediated damage at the neuromuscular junction. Reducing this damage is thought to improve signaling between nerves and muscles.

The FDA first approved Zilbrysq in the prefilled syringe on October 17, 2023, based on positive results from the 12-week phase 3 RAISE trial (NCT04115293). The autoinjector was approved on October 16, 2026, and UCB expects it to be available in the US in the first quarter of 2027. Study DV0012 showed that Zilbrysq given with the autoinjector reaches the same levels in the body as Zilbrysq given with the prefilled syringe (bioequivalence). Study DV0013 looked at people with gMG injecting themselves with the autoinjector.

• Used for: generalized myasthenia gravis in adults who are AChR antibody positive
• Drug class: complement inhibitor (C5 inhibitor). It is a small synthetic peptide, not a monoclonal antibody.
• How it is given: subcutaneous (under the skin) injection, by you or a caregiver
• How often: once a day, at about the same time each day
• Dose: based on your body weight (16.6 mg, 23 mg or 32.4 mg)
• Device options: prefilled syringe or prefilled autoinjector
• Boxed warning: serious meningococcal infections. Available only through the Zilbrysq REMS program.
• Who can use it: adults only. It has not been studied in children.

Zilbrysq is used to treat generalized myasthenia gravis (gMG) in adults who have antibodies against the acetylcholine receptor (AChR). This is called AChR antibody-positive, or AChR-Ab+.

It is not approved for use in children or in people with myasthenia gravis who do not have AChR antibodies.

Zilbrysq works by attaching to the complement protein C5 and stopping it from being split into its active parts, C5a and C5b. This blocks the complement system before it can form the membrane attack complex (C5b-9), which damages the neuromuscular junction. With less damage, nerve signals reach the muscles more easily, and myasthenia gravis symptoms improve.

Myasthenia gravis is a long-term (chronic) autoimmune disease that causes muscle weakness. Symptoms can include double vision, drooping eyelids, and trouble talking, swallowing, breathing and walking. The weakness usually gets worse with activity and later in the day, and improves with rest.

In myasthenia gravis, your immune system makes antibodies that attack the receptors where nerves signal muscles to contract (the neuromuscular junction). In people who are AChR antibody positive, these antibodies also switch on the complement system, part of the immune system that damages the neuromuscular junction. Symptoms often start in the eye muscles and may spread over time to a generalized form that affects the arms, legs, and the muscles used for swallowing and breathing.

Zilbrysq can start to improve myasthenia gravis symptoms within the first week. In the long-term RAISE-XT study (NCT04225871), people who switched from placebo to Zilbrysq had rapid improvements in daily function (MG-ADL score) within the first week of starting treatment. Improvements continued over the first 12 weeks and lasted for more than a year (60 weeks) of treatment.

This fast start fits with how quickly Zilbrysq blocks complement. By the end of the first week, it blocked about 97.5% of complement activity.

Read more: How long before Zilbrysq works?

Zilbrysq was approved based on the 12-week phase 3 RAISE study (NCT04115293). This randomized, double-blind, placebo-controlled study enrolled 174 adults with AChR antibody-positive gMG. People received either Zilbrysq (86 people) or placebo (88 people) once a day, in addition to their usual MG treatment.

Improvement in gMG was measured with MG-ADL (Myasthenia Gravis Activities of Daily Living) and QMG (Quantitative Myasthenia Gravis) scores. For both scores, a bigger drop means a bigger improvement:

• MG-ADL: measures how gMG affects 8 daily activities, such as talking, chewing, swallowing and breathing. It is scored from 0 to 24.
• QMG: a muscle strength test done by a clinician. It is scored from 0 to 39.

At week 12, compared with placebo, Zilbrysq improved MG-ADL scores by an extra 2.09 points and QMG scores by an extra 2.94 points (both statistically significant).

Zilbrysq is given once a day as an injection under the skin (subcutaneous injection), using a single-dose prefilled syringe or prefilled autoinjector. Your healthcare provider will show you or your caregiver how to inject Zilbrysq before you use it for the first time. Follow the Instructions for Use for your device (syringe or autoinjector).

• Get your blood tests and vaccines first. Your lipase and amylase levels are checked, and your meningococcal vaccines must be up to date, before your first dose.
• Inject once a day at about the same time each day.
• Let it warm up. If your Zilbrysq is stored in the refrigerator, take out 1 syringe or autoinjector and leave it on a clean, flat surface out of direct sunlight for 30 to 45 minutes to reach room temperature. Do not heat it or put it in the microwave. Put the rest of the carton straight back in the refrigerator.
• Check the medicine. It should be clear to slightly opalescent (pearly) and colorless. Do not use it if it is cloudy or has particles in it.
• Choose an injection site. Inject into the stomach area (abdomen), thighs, or the back of the upper arms, in skin that is not tender, bruised, red or hard. Avoid scars and stretch marks. Only a caregiver should inject into the upper, outer arm.
• Rotate injection sites each time you inject.
• Inject the full dose. Each syringe or autoinjector is single-dose only. Do not reuse it.
• Throw it away safely. Put the used syringe or autoinjector in an FDA-cleared sharps disposal container right after use.

Both Zilbrysq devices contain the same medicine in the same 3 strengths, are used once a day, and can be used by you or a caregiver. Studies showed that the amount of Zilbrysq absorbed into the body was similar with the autoinjector and the prefilled syringe.

Ask your healthcare provider which device is right for you. Neither device is made with natural rubber latex.

Boxed warning: serious meningococcal infections

Zilbrysq affects part of your immune system and increases your risk of serious, life-threatening or fatal meningococcal infections (caused by Neisseria meningitidis bacteria). These infections can cause meningitis or blood infections, and can become life-threatening or fatal quickly if they are not recognized and treated early.

• You must complete or update your meningococcal vaccines (for serogroups A, C, W, Y and B) at least 2 weeks before your first dose of Zilbrysq, unless your healthcare provider decides you need to start treatment right away.
• If you need to start Zilbrysq urgently and are not up to date with your vaccines, you will receive antibiotics, and you should get your vaccines as soon as possible.
• If you had a meningococcal vaccine in the past, you may need more doses. Your healthcare provider will check whether you need to be revaccinated during treatment.
• Vaccines lower the risk but do not prevent all meningococcal infections.

Get emergency medical care right away if you have any of these symptoms of a meningococcal infection:

• fever
• fever with a rash
• fever with a fast heartbeat
• headache with nausea or vomiting
• headache with fever
• headache with a stiff neck or stiff back
• confusion
• muscle aches with flu-like symptoms
• eyes sensitive to light

Your healthcare provider will give you a Patient Safety Card. Carry it with you at all times during treatment and for 2 months after your last dose, because your risk of meningococcal infection can continue after you stop Zilbrysq. Show the card to any healthcare provider who treats you, so they can diagnose and treat you quickly.

Zilbrysq REMS program

Because of the risk of meningococcal infections, Zilbrysq is only available through a restricted program called the Zilbrysq REMS (Risk Evaluation and Mitigation Strategy). Before you can receive Zilbrysq, your healthcare provider must:

• enroll in the Zilbrysq REMS
• counsel you about the risk of meningococcal infection
• give you the Patient Guide, which includes the signs and symptoms of meningococcal infection
• give you a Patient Safety Card
• make sure you are vaccinated against meningococcal infection, and give you a prescription for antibiotics if you must start Zilbrysq before you are up to date with your vaccines

Zilbrysq can only be dispensed by pharmacies that are certified in the REMS. For more information, visit www.ZILBRYSQREMS.com or call 1-877-414-8353.

Other serious infections

Zilbrysq may increase your risk of other serious infections, especially those caused by encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and other Neisseria species, including gonorrhea. Your healthcare provider will tell you whether you need vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b.

Some people may have a higher risk of gonorrhea infection. Talk to your healthcare provider about whether you are at risk, how to prevent gonorrhea, and regular testing.

Call your healthcare provider right away if you have new signs or symptoms of infection.

Pancreatitis and pancreatic cysts

Pancreatitis and pancreatic cysts have been reported with Zilbrysq. In the long-term extension studies, about 3.3% of people had a pancreatic problem (1.9% had pancreatitis and 1.4% had pancreatic cysts). Your healthcare provider will check your pancreas enzymes (lipase and amylase) before you start. Call your healthcare provider right away if you have stomach pain that does not go away, which may spread to your back, with or without vomiting. Your healthcare provider will tell you whether you should stop Zilbrysq.

You should not start Zilbrysq if you have a serious meningococcal (Neisseria meningitidis) infection that has not cleared up.

Tell your healthcare provider about all of your medical conditions, including if you:

• have an infection or a fever
• have had pancreatitis or other pancreas problems
• have not had your meningococcal vaccines, or are not sure if they are up to date
• have severe liver problems. Zilbrysq has not been studied in people with severe liver impairment.
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed

Pregnancy

Based on animal studies, Zilbrysq may harm an unborn baby. In studies in pregnant monkeys, zilucoplan caused an increase in pregnancy loss at doses similar to human doses. There is no information on Zilbrysq use in pregnant women. Tell your healthcare provider if you are pregnant or plan to become pregnant.

Pregnancy registry: there is a registry that collects information on the outcomes of women exposed to Zilbrysq during pregnancy or breastfeeding. You or your healthcare provider can contact UCBCares at 1-844-599-2273 or [email protected].

Breastfeeding

It is not known if Zilbrysq passes into breast milk or affects a breastfed baby. Talk to your healthcare provider about the best way to feed your baby if you use Zilbrysq.

Common Zilbrysq side effects

The most common side effects of Zilbrysq (in 10% or more of people) are injection site reactions, upper respiratory tract infections and diarrhea.

Side effects reported in 5% or more of people taking Zilbrysq, and more often than with placebo, in the RAISE study:

• injection site reactions, such as bruising, pain or redness (29%)
• upper respiratory tract infection (14%)
• diarrhea (11%)
• urinary tract infection (8%)
• nausea or vomiting (8%)
• increased lipase, a pancreas enzyme, on blood tests (7%)
• increased amylase, a pancreas enzyme, on blood tests (5%)

Skin hardening (morphea) with long-term use. Morphea causes patches of hard, thickened or discolored skin. In long-term studies, it was reported in about 5% of people using Zilbrysq. Most cases started more than 1 year after starting treatment and were mild to moderate. Tell your healthcare provider if you notice new patches of firm, thick or discolored skin.

Serious Zilbrysq side effects

Serious meningococcal infections. Zilbrysq has a boxed warning for meningococcal infections, which can become life-threatening quickly. See Warnings for the symptoms to watch for.

Inflammation of the pancreas (pancreatitis) and other pancreatic problems. Pancreatitis and pancreatic cysts have been reported in people using Zilbrysq. Your healthcare provider will check your lipase and amylase levels with a blood test before you start treatment. Call your healthcare provider right away if you have stomach (abdominal) pain that will not go away. The pain may be severe, may spread from your abdomen to your back, and may happen with or without vomiting. Your healthcare provider will tell you whether you should stop Zilbrysq.

Tell your healthcare provider about any side effect that bothers you or does not go away.

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.

Your Zilbrysq dose is based on your actual body weight and is given once a day by subcutaneous injection.

Notes:

• Your healthcare provider may change your dose if your weight changes into a different weight range.
• Zilbrysq is not approved for children.

Zilbrysq is available as a clear to slightly opalescent, colorless solution in single-dose prefilled syringes or single-dose prefilled autoinjectors:

• 16.6 mg/0.416 mL
• 23 mg/0.574 mL
• 32.4 mg/0.81 mL

If you miss a dose of Zilbrysq, inject it as soon as you can. Then inject your next dose at your regular time. Do not inject more than 1 dose in a day. Call your healthcare provider if you are not sure what to do.

In case of overdose, call the poison control helpline at 1-800-222-1222. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services at 911.

Formal drug interaction studies have not been done with Zilbrysq. Lab studies suggest it is unlikely to affect, or be affected by, medicines that are processed by the main liver enzymes (CYP enzymes) or carried by common drug transporters.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal supplements, and the vaccines you receive. Keep a list to show your healthcare provider and pharmacist when you get a new medicine.

Other drugs may interact with this medicine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Healthcare professionals and patients often use the Zilbrysq Prescribing Information for more detail about this medicine, including indications and usage, dosage and administration, clinical pharmacology, clinical studies and more. The Prescribing Information is sometimes called the Zilbrysq package insert or FDA label. It does not take the place of talking to your healthcare provider about your treatment.

Storage is the same for the prefilled syringe and the autoinjector.

In the refrigerator: store at 2°C to 8°C (36°F to 46°F) in the original carton until the expiration date on the carton.

At room temperature: you can store Zilbrysq at up to 30°C (86°F) in the original carton for one single period of up to 3 months, or until the expiration date, whichever comes first.

• Write the date you took it out of the refrigerator in the space on the carton.
• Throw it away if it is not used within 3 months, or once the expiration date has passed.
• Do not put Zilbrysq back in the refrigerator after it has been stored at room temperature.

Also:

• Do not freeze.
• Keep Zilbrysq in the original carton to protect it from light until you are ready to use it.
• Zilbrysq has no preservative. Throw away any unused medicine left in the syringe or autoinjector.
• Keep out of reach of children.

Active ingredient: zilucoplan

Inactive ingredients: dibasic sodium phosphate (anhydrous), monobasic sodium phosphate (monohydrate), sodium chloride, and water for injection

Zilbrysq is manufactured for: UCB, Inc., 1950 Lake Park Drive, Smyrna, GA 30080.