General Information

Zilbrysq (zilucoplan) is a complement inhibitor.

Zilbrysq is specifically indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Dosing/Administration

Zilbrysq is supplied as an injection for subcutaneous administration.

Vaccination and Prophylaxis for Meningococcal Infection

• Vaccinate patients for meningococcal infection (serogroups A, C, W, and Y [MenACWY] and serogroup B [MenB]) according to current ACIP recommendations at least 2 weeks prior to administering the first dose of Zilbrysq.
• If urgent Zilbrysq therapy is indicated in a patient who is not up to date with vaccines for both MenACWY and MenB according to ACIP recommendations, administer meningococcal vaccine(s) as soon as possible and provide the patient with antibacterial drug prophylaxis. Healthcare providers who prescribe Zilbrysq must enroll in the Zilbrysq REMS.

Recommended Testing Before Initiating Zilbrysq

• Before initiating Zilbrysq, obtain baseline lipase and amylase levels 

Recommended Dosage

• The recommended dosage of Zilbrysq is given once daily as a subcutaneous injection and is dependent on actual body weight:

Mechanism of Action

Zilbrysq (zilucoplan) binds to the complement protein C5 and inhibits its cleavage to C5a and C5b, preventing the generation of the terminal complement complex, C5b-9. The precise mechanism by which zilucoplan exerts its therapeutic effect in generalized myasthenia gravis is unknown but is presumed to involve reduction of C5b-9 deposition at the neuromuscular junction.

Side Effects

Adverse effects associated with the use of Zilbrysq may include, but are not limited to, the following:

• injection site reactions
• upper respiratory tract infection
• diarrhea

The Zilbrysq drug label comes with the following Black Box Warning: 

• Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors; Zilbrysq is a complement inhibitor. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. 
• Complete or update meningococcal vaccination at least 2 weeks prior to administering the first dose of Zilbrysq, unless the risk of delaying therapy outweighs the risk of developing a meningococcal infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccinations in patients receiving a complement inhibitor. 
• Persons receiving Zilbrysq are at increased risk for invasive disease caused by N. meningitidis, even if they develop antibodies following vaccination. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected. 
• Zilbrysq is available only through a restricted program called Zilbrysq REMS.

Clinical Trial Results

The FDA approval of Zilbrysq was based on data from the RAISE study, a multi-center, Phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy, safety profile, and tolerability of Zilbrysq in adult patients with anti-acetylcholine receptor (AChR) antibody-positive gMG. Patients were randomized in a 1:1 ratio to receive daily subcutaneous injections of 0.3 mg/kg Zilbrysq or placebo for 12 weeks. 

The primary endpoint for the RAISE study was change from baseline to Week 12 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score. The MG-ADL is an eight-item patient-reported outcome measure assessing MG symptoms and functional activities related to activities of daily living. These include activities such as breathing, talking, swallowing, and being able to rise from a chair. Each of the items is scored, from 0 (normal) to 3 (most severe), providing a total MG-ADL score ranging from 0 to 24, where higher scores indicate greater severity of symptoms.

The efficacy of Zilbrysq was also measured, as a secondary endpoint, using the Quantitative Myasthenia Gravis (QMG) total score which is a 13-item categorical grading system that assesses muscle weakness. Each item is assessed on a 4-point scale where a score of 0 represents no weakness and a score of 3 represents severe weakness. A total possible score ranges from 0 to 39, where higher scores indicate more severe impairment.

At week 12, treatment with Zilbrysq demonstrated a statistically significant improvement from baseline compared to placebo for MG-ADL total score and QMG total score. Other secondary endpoints included the proportion of patients with improvements of at least 3 and 5 points in the MG-ADL total score and QMG total score, respectively, at Week 12 without rescue therapy.