Zilbrysq Drug Information

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

Recommended Vaccination and Prophylaxis for Meningococcal Infection Vaccinate patients against meningococcal infection (serogroups A, C, W, Y, and B) according to current ACIP recommendations at least 2 weeks prior to initiation of ZILBRYSQ. If urgent ZILBRYSQ therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible. 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 (see Table 1 ). Table 1: Total Daily Dosage by

Preparation Instructions

ZILBRYSQ prefilled syringes can be stored in a refrigerator in the original carton. ZILBRYSQ can also be stored at room temperature in the original carton for up to 3 months or until the expiration date, whichever occurs first. If stored in the refrigerator: Before injecting, take 1 ZILBRYSQ prefilled syringe out of the refrigerator and place it on a clean, flat surface.

Allow ZILBRYSQ to reach room temperature out of direct sunlight (30 to 45 minutes). Do not heat or place in microwave. Immediately return the carton with the other prefilled syringes to the refrigerator.

If stored at room temperature: Remove 1 ZILBRYSQ prefilled syringe from the carton. Do not return ZILBRYSQ to the refrigerator after it has been stored at room temperature. Visually inspect ZILBRYSQ for particulate matter and discoloration prior to administration.

ZILBRYSQ is a clear to slightly opalescent, colorless solution. Do not use if the solution contains visible particles, is cloudy, or if foreign particulate matter is present. ZILBRYSQ does not contain preservatives; unused portions of drug remaining in the syringe should be discarded.

Each prefilled syringe is single-dose only.

Administration Instructions ZILBRYSQ is intended for use under the guidance and supervision of a healthcare professional. Patients may self-inject ZILBRYSQ after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of ZILBRYSQ according to the "Instructions for Use".

Administer ZILBRYSQ subcutaneously into areas of the abdomen, thighs, or back of the upper arms that are not tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks. Rotate injection sites for each administration.

Administration of ZILBRYSQ in the upper, outer arm should be performed by a caregiver. When using ZILBRYSQ prefilled syringes, inject the full contents of the single-dose prefilled syringe. Discard ZILBRYSQ prefilled syringe after use.

Do not reuse. Instruct the patient that the daily dose should be administered at approximately the same time each day. If a dose is missed, administer the dose as soon as possible.

Thereafter, resume dosing at the regular scheduled time. Do not administer more than 1 dose per day.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 212 patients were treated with ZILBRYSQ 0.3 mg/kg in clinical studies in gMG. In a placebo-controlled study (Study 1) in patients with gMG, 86 patients received ZILBRYSQ 0.3 mg/kg.

The mean age at study entry was 52.6 years (range 21 to 75 years). Table 2 summarizes the adverse reactions reported in at least 5% of patients treated with ZILBRYSQ and more frequently than placebo. The most common adverse reactions (reported in at least 10% of patients treated with ZILBRYSQ) were injection site reactions, upper respiratory tract infections, and diarrhea.

Table 2: Adverse Reactions in at least 5% of Patients Treated with ZILBRYSQ and More Frequently than in Patients who Received Placebo in Study 1 5 1 Pancreatic Events In addition to increases in amylase and lipase observed in Study 1, pancreatic events, including pancreatitis and pancreatic cysts have been observed in patients taking ZILBRYSQ. Adverse Laboratory Changes in Clinical Trials Additional laboratory abnormalities included transient elevations of blood eosinophils, which were of uncertain clinical significance.

Postmarketing Experience Adverse Reactions from Observational Studies Morphea In the open-label extension studies, which included 213 patients, morphea was observed in 10 (5%) patients; most cases had a time to onset longer than one year after start of treatment and were mild to moderate in severity. One patient discontinued ZILBRYSQ because of morphea.

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ZILBRYSQ during pregnancy. Patients or healthcare providers may contact UCBCares at 1-844-599-CARE or email [email protected], so that information about the exposure of ZILBRYSQ during pregnancy and/or breastfeeding can be collected. Risk Summary There are no available data on ZILBRYSQ use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Administration of zilucoplan to pregnant monkeys resulted in increases in embryofetal death at maternal exposures similar to those in humans at therapeutic doses (see Animal Data ). All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background rate of major birth defects and miscarriage in the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Data Animal Data Subcutaneous administration of zilucoplan mg/kg/day to pregnant monkeys throughout gestation resulted in an increase in embryofetal death at all doses, in the absence of maternal toxicity. A no effect dose for adverse developmental effects in monkeys was not identified.

The lowest dose tested was associated with maternal exposures (AUC) similar to that in humans at the maximum recommended human dose of 32.4 mg/day. Data from an ex vivo human placental transfer model demonstrated transfer of zilucoplan into the fetal compartment at a rate of 0.5% at a steady state plasma concentration of 10 µg/mL zilucoplan, which corresponds to a therapeutic dose of 0.3 mg/kg. The clinical significance of these data in human pregnancies is unknown.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

ZILBRYSQ is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection.