Zilbrysq (zilucoplan) is a newly FDA-approved complement inhibitor used to treat generalized myasthenia gravis (gMG) in patients who are AChR antibody positive (AChR-Ab+). Zilbrysq is a C5 inhibitor (complement component 5 inhibitor) that works by blocking C5, a protein in the immune system that is involved with the symptoms of generalized myasthenia gravis. Zilbrysq is the first once-daily, under-the-skin injection that can be self-administered by MG patients. 

Zilbrysq became an FDA-approved medication on October 17, 2023, based on positive results from the 12-week phase 3 trial RAISE (NCT04115293). Zilbrysq is indicated for adult patients with generalized myasthenia gravis that is antiacetylcholine receptor (AChR) antibody positive. Zilbrysq showed rapid and clinically meaningful improvements in symptoms of MG, compared to a placebo, measured using the MG-ADL score.

What is myasthenia gravis?

Myasthenia gravis is a long-term (chronic) autoimmune disease that causes muscle weakness, leading to symptoms of double vision, drooping eyelids, trouble talking, breathing, and trouble walking. Myasthenia gravis is caused by antibodies from your immune blocking or attacking receptors between nerves and muscles,  which makes it harder for the muscles to contract. Many patients with myasthenia gravis have antibodies that attack the nicotinic acetylcholine receptors (AChR), these patients are called AChR antibody positive (AChR-Ab+).

Usually the first and main symptom in MG is painless weakness of specific muscles that gets worst towards the end of the day and also may becomes worse during physical activity and then improves after rest. MG symptoms often starts with eye weakness; then over a period of time symptom may progress to a severe generalized form, with weakness in arms and legs, or in muscles involved in swallowing and breathing.

The complement system is part of the immune system that becomes activated in MG, damaging the neuromuscular junction and causing symptoms of MG. 

Zilbrysq affects part of your immune system and may lower the ability of your immune system to fight certain infections, therefore increasing your chance of getting serious and life-threatening meningococcal infections.

• Meningococcal infections may become life-threatening or fatal if not recognized and treated early. You must complete or update two types of meningococcal vaccines (for both serogroup B infections and serogroup A, C, W, and Y infections) at least 2 weeks before your first dose of this medicine if you have not already had these vaccines.
• If your healthcare provider decides that urgent treatment with Zilbrysq is needed, you should receive meningococcal vaccination(s) as soon as possible. 
• If you have not completed or updated vaccinations for meningococcal infections at least 2 weeks before your first Zilbrysq dose and therapy must be started right away, you must also receive antibiotics. 
• If you had a meningococcal vaccine in the past, you might need additional vaccination before starting this medicine. Your healthcare provider will decide if you need additional meningococcal vaccination. 
• Meningococcal vaccines do not prevent all meningococcal infections. Call your healthcare provider or get emergency medical care right away if you get any of these signs and symptoms of a meningococcal infection:  headache with nausea or vomiting, confusion,  headache and fever, muscle aches with flu-like symptoms, headache with a stiff neck or stiff back, eyes sensitive to light, fever,  and fever with a rash.

Your healthcare provider will give you a Patient Safety Card about the risk of meningococcal infection. Carry it with you at all times during treatment and for 2 months after your last dose. Your risk of meningococcal infection may continue for several weeks after your last dose of this medicine. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly. 

Zilbrysq is only available through a program called the Zilbrysq REMS. Before you can receive this medicine, your healthcare provider must: 

• enroll in the Zilbrysq REMS. 
• counsel you about the risk of meningococcal infection. 
• give you the Patient Guide, including information about the signs and symptoms of meningococcal infection. 
• give you a Patient Safety Card about your risk of meningococcal infection, as discussed above. 
• make sure you are vaccinated with two types of meningococcal vaccine and, if needed, get revaccinated with the meningococcal vaccines. Ask your healthcare provider if you are unsure if you need to be revaccinated. 

Zilbrysq may also increase the risk of other types of serious infections. This injection may increase your chance of getting Streptococcus pneumoniae and Haemophilus influenzae type b. Your healthcare provider will tell you if you should receive the Streptococcus pneumoniae and Haemophilus influenzae type b vaccinations. 

Certain people may have an increased risk of gonorrhea infection. Talk to your healthcare provider about whether you are at risk for gonorrhea infection, about gonorrhea prevention, and about regular testing. 

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

Your doctor or healthcare provider will give you the detailed Instructions for Use that come with your injection. This has information on how to prepare and use this medicine and how to throw away the used prefilled syringes properly. Use this medicine exactly as prescribed by your healthcare provider after proper training on how to prepare and inject Zilbrysq.

Zilbrysq instructions

• Zilbrysq is given as a daily injection under the skin (subcutaneous) using a prefilled syringe. The daily dose should be administered at approximately the same time each day. 
• Zilbrysq is injected into areas of the abdomen, thighs, or back of the upper arms that are not tender, bruised, red, or hard. You should not inject into skin areas with scars or stretch marks. Only a caregiver can give Zilbrysq in the upper, outer arm.
• Rotate injection sites for each administration.

Your healthcare provider will decide the total daily dose depending on your body weight. 

Each prefilled syringe is for single-use only. Throw away the prefilled syringe after each use. Do not reuse. 

The recommended adult Zilbrysq dose is based on actual body weight.

• Less than 56kg = 16.mg daily
• 56 kg to less than 77 kg = 23 mg daily
• 77 kg and above = 32.4 mg.

What strengths is Zilbrysq available as?

Zilbrysq is available as prefilled syringes as 16.6 mg/0.416 mL, 23 mg/0.574 mL, or 32.4 mg/0.81 mL.

You should not use this medicine if you have a Neisseria meningitidis infection.

Before taking this medicine

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

• have an infection or fever.

Pregnancy

Tell your healthcare provider if you are pregnant or plan to become pregnant , as It is not known if Zilbrysq will harm your unborn baby. 

Breastfeeding

Tell your healthcare provider if you are breastfeeding or plan to breastfeed as it is not known if Zilbrysq  passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you are using this medicine.

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