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

Injection: 16.6 mg/0.416 mL, 23 mg/0.574 mL, or 32.4 mg/0.81 mL of zilucoplan as a clear to slightly opalescent, colorless solution in single-dose prefilled syringes.

ZILBRYSQ is contraindicated for initiation in patients with unresolved serious Neisseria meningitidisinfection [see Warnings and Precautions (5.1)] .

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:

• Serious Meningococcal Infections [see Warnings and Precautions (5.1)]
• Other Infections [see Warnings and Precautions (5.3)]
• Pancreatitis and Other Pancreatic Conditions [see Warnings and Precautions (5.4)]

Zilucoplan, a complement inhibitor, is a 15 amino-acid, synthetic macrocyclic peptide.

The molecular formula of zilucoplan is C 172H 278N 24O 55in free acid form and its molecular weight is 3562.23 Daltons (free acid form).

The chemical name for zilucoplan sodium is: acetyl‐[L-lysyl 1-L-valyl 2-L-glutamyl 3-L-arginyl 4-L phenylalanyl 5-L aspartyl 6]- N-methyl L-aspartyl 7-L tert-leucyl 8-L tyrosyl 9-L-7-azatryptophyl 10-L glutamyl 11-L-tyrosyl 12-L prolyl 13-L cyclohexylglycyl 14-[L-lysyl 15, Nε-palmitoyl-γ-L-glutamyl-(1-amino-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45,48,51,54,57,60,63,66,69,72-tetracosaoxapentaheptacontan-75-oyl)], cyclic (Lactam 1-6), tetra sodium.

The primary structure for zilucoplan sodium is shown below:

ZILBRYSQ injection is a sterile, clear to slightly opalescent, colorless, preservative-free, buffered solution of zilucoplan (as zilucoplan sodium) for subcutaneous injection, in single-dose prefilled syringes. The solution pH is between 6.5 and 7.5. ZILBRYSQ is supplied in three dose strengths containing 16.6 mg /0.416 mL, 23 mg /0.574 mL, and 32.4 mg/0.81 mL of zilucoplan free acid equivalent to 17 mg, 23.6 mg, and 33.2 mg of zilucoplan sodium, respectively. Additionally, each mL of the solution contains dibasic sodium phosphate, anhydrous (4.11 mg); monobasic sodium phosphate, monohydrate (2.9 mg); sodium chloride (4.42 mg); and water for injection.

The efficacy of ZILBRYSQ for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-AChR antibody positive was established in a 12-week, multicenter, randomized, double-blind placebo-controlled study (Study 1; NCT04115293).

Study 1 enrolled patients who met the following criteria at screening:

• Myasthenia Gravis Foundation of America (MGFA) clinical classification class II to IV,
• Positive serology for AChR binding autoantibodies,
• MG-Activities of Daily Living (MG-ADL) total score of ≥6,
• Those on MG therapy prior to screening (including acetylcholinesterase (AChE) inhibitors, steroids, or non-steroidal immunosuppressive therapies (NSISTs), either in combination or alone), needed to maintain a stable dose.

A total of 174 patients were enrolled in Study 1 and were randomized 1:1 to receive either ZILBRYSQ 0.3 mg/kg (n=86) or placebo (n=88) once daily by subcutaneous injection. Baseline characteristics were similar between treatment groups. Patients had a mean age of 53.0 years and a mean time since diagnosis of 9 years. Fifty-seven percent of the patients were female, 74% were White, 12% were Asian, 8% were Black, 1% were American Indian or Alaska Native, and 6% did not have race reported. The mean baseline MG-ADL total score was 10.6 (range 6 to 19).

At baseline, approximately 85% of patients in each group received cholinesterase inhibitors, 63% received steroids, and 51% received NSISTs, at stable doses.

The primary efficacy endpoint was a comparison of the change from baseline between treatment groups in the Myasthenia Gravis-Specific Activities of Daily Living scale (MG-ADL) total score after twelve weeks of treatment. The MG-ADL assesses the impact of gMG on daily functions of 8 signs or symptoms that are typically affected in gMG. Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. A total score ranges from 0 to 24, with the higher scores indicating more impairment.

The efficacy of ZILBRYSQ was also measured 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.

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.

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 (Table 3; Figure 1).

Figure 1: Change from Baseline in MG-ADL Total Score (A) and QMG Total Score (B) through Week 12

*Analysis based on MMRM ANCOVA model

The proportion of MG-ADL responders with at least a 3-point improvement at week 12 was greater for ZILBRYSQ (73.1%) compared to placebo (46.1%) (p<0.001). The proportion of QMG responders with at least a 5-point improvement was also greater for ZILBRYSQ (58%) compared to placebo (33%) (p = 0.0012). The proportion of clinical responders at higher response thresholds was consistently greater for ZILBRYSQ compared to placebo.

Advise the patients and/or caregivers to read FDA-approved patient labeling (Medication Guide and Instructions for Use) .

Manufactured for:
UCB, Inc.
1950 Lake Park Drive
Smyrna, GA 30080

ZILBRYSQ ®is a registered trademark of the UCB Group of Companies.
©2024 UCB, Inc., Smyrna, GA 30080. All rights reserved.

ZILBRYSQ ®(ZIL-brisk)
(zilucoplan)
injection, for subcutaneous use
Single-Dose Prefilled Syringe

This Instructions for Use contains information on how to inject ZILBRYSQ.

Understanding Your ZILBRYSQ Prefilled Syringe

Read this Instructions for Use before using the ZILBRYSQ prefilled syringe. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. See the Medication Guidethat comes with ZILBRYSQ for important information.

Your healthcare provider should show you how to prepare and inject ZILBRYSQ prefilled syringe properly before you use it for the first time. Do not inject yourself or someone else until you have been shown how to inject ZILBRYSQ correctly.

Keep this Instructions for Use and refer to it as needed until you have used all of the ZILBRYSQ prefilled syringes in the packaging.

For general questions or help, please call your healthcare provider or UCBCares at 1-844-599-CARE (2273).

How Should I Store ZILBRYSQ Prefilled Syringes?

• Store ZILBRYSQ prefilled syringes in a refrigerator between 36°F to 46°F (2°C to 8°C) until the expiration date on the carton. Do not freeze ZILBRYSQ.
• ZILBRYSQ prefilled syringes may be stored at room temperature up to 86°F (30°C) in the original carton for a single period of up to 3 months. Write the date you removed the prefilled syringes from the refrigerator in the space provided on the carton. After ZILBRYSQ prefilled syringes have been stored at room temperature, do not place them back in the refrigerator. Throw them away if not used within 3 months or if the expiration date has passed, whichever occurs first.
• Keep the ZILBRYSQ prefilled syringes in the original carton before use.
• Keep ZILBRYSQ prefilled syringes and all medicines out of the reach of children.

Important Information You Need to Know Before You Inject ZILBRYSQ

• Do notuse ZILBRYSQ if the expiration date on the packaging has passed or the carton seals have been broken.
• Do notreuse the ZILBRYSQ prefilled syringe. The prefilled syringe is for 1-time (single use) only. You may get an infection.
• Do notinject ZILBRYSQ more than 1 time per day.
• Do notmiss any doses of ZILBRYSQ. If you miss your ZILBRYSQ dose, inject a dose as soon as possible. Then, inject the next dose at your scheduled time. Do not inject more than 1 dose each day.
• Do notuse the ZILBRYSQ prefilled syringe if it has been dropped.
• Do notremove the needle cap from the ZILBRYSQ prefilled syringe until you are ready to inject.
• Do notinsert the needle into the skin more than 1 time because this may bend or break the needle, causing trauma to the tissue.
• Do notpull back on the ZILBRYSQ prefilled syringe plunger head at any time because this can break the prefilled syringe.
• Do nottouch the needle guard activation clips at any time because this can cause the early activation of the needle guard.

ZILBRYSQ Prefilled Syringe Guide to Parts (Figure A):

Preparing for Injection

Step 1: Take out the ZILBRYSQ prefilled syringe

If the ZILBRYSQ prefilled syringes are stored in the refrigerator:

• Take the ZILBRYSQ prefilled syringes carton out of the refrigerator and remove 1 prefilled syringe from the carton. Grasp the prefilled syringe body.Carefully lift the prefilled syringe straight up out of the tray (Figures B.1 and B.2). Put the rest of the prefilled syringes in the carton back in the refrigerator.
• Before you inject ZILBRYSQ, let the prefilled syringe warm up to room temperature on a clean flat surface for 30 to 45 minutes. This will help to reduce discomfort when injecting.
• Do not warm the ZILBRYSQ prefilled syringe in any other way (for example in a microwave, in hot water, or in direct sunlight).
• Do not remove the needle cap from the prefilled syringe until you are ready to inject.

If the ZILBRYSQ prefilled syringes are stored at room temperature:

• Remove 1 ZILBRYSQ prefilled syringe from the carton. Grasp the prefilled syringe body.Carefully lift the prefilled syringe straight up out of the tray ( Figures B.1 and B.2). Any remaining prefilled syringes in the carton should not be placed in the refrigerator after it has been stored at room temperature.
  

  Figure B.1	Figure B.2

Step 2: Inspect the ZILBRYSQ prefilled syringe

• Check the prefilled syringe for damage (Figure C).
• Do notuse if any part of the prefilled syringe appears to be cracked, leaking, or broken.
• Check thatthe needle cap is not cracked or broken and attached to the prefilled syringe (Figure C).
• Do notuse if the needle cap is missing or not securely attached.
• Check the expiration date and medicine name (ZILBRYSQ) on the prefilled syringe label (Figure C).
• Do notuse if the expiration date printed on the prefilled syringe has passed.
• Do notuse if the word ZILBRYSQ does not appear on the prefilled syringe.
• Check the dose appearing on the label (Figure C)and make sure it matches your prescribed dose.
• Do notuse if the dose does not match your prescribed dose.
• Check the medicine inside the prefilled syringe (Figure C). The medicine should be clear to almost clear and colorless. It is normal to see air bubbles in the prefilled syringe.
• Do notuse if the medicine is cloudy, discolored, or contains floating particles.
  

  Figure C

Step 3: Gather supplies

Wash your hands with soap and water and dry them with a clean towel.

Gather the following supplies on a clean, flat surface (Figure D):

• 1 ZILBRYSQ prefilled syringe
• 1 alcohol wipe (not supplied)
• 1 cotton ball or gauze pad (not supplied)
• 1 adhesive bandage (not supplied)
• 1 sharps disposal or puncture-resistant container (not supplied). See Step 12for instructions on throwing away the syringe.
  

  Figure D

Step 4: Choose your injection site

Choose an injection site from the following areas (Figures E.1 and E.2):

• The stomach (abdomen), except for the 2-inch area around the belly button (navel) (Figure E.1)
• The front of the thighs (Figure E.1)
  

  Figure E.1 – abdomen and thighs

• The back of the upper arms (only if someone else is giving you the injection) (Figure E.2)
  

  Figure E.2 – upper arms

Choose a different site each time you give yourself an injection. If you want to use the same injection site, make sure it is at least 1-inch from a spot you used before.

Do notinject ZILBRYSQ into an area that is red, tender, bruised, swollen, hard or that has scars or stretch marks.

Step 5: Clean your injection site

Clean the injection site using an alcohol wipe (Figure F).

Let the skin dry for 10 seconds before injecting.

Do nottouch the injection site again before giving your injection.

Injecting the Medicine

Step 6: Remove the needle cap

Hold the body of the ZILBRYSQ prefilled syringe with one hand and pull the needle cap straight off with your other hand (Figure G).

Throw away (discard) the needle cap into your household trash or a sharps disposal container.

Do nottouch the needle or let it touch anything.

Do notrecap the needle at any time to avoid injury.

Do nottry to remove any air bubbles from the ZILBRYSQ prefilled syringe. Air bubbles will not affect your dose and will not harm you. This is normal. You can continue to take your injection.

Step 7: Pinch your injection site

Use your other hand to pinch the area of cleaned skin and hold it firmly (Figure H).

Step 8: Insert the needle

Insert the entire needle into the pinched skin at a 45° to 90° angle. When the needle is fully inserted, hold the ZILBRYSQ prefilled syringe in place (Figure I).

Do notpull back on the plunger head at any time because this could break the prefilled syringe.

Do nottouch the needle guard activation clips.

Step 9: Release the pinched skin

When the needle is fully inserted, hold the ZILBRYSQ prefilled syringe in place and release the pinched skin (Figure J).

Do notreinsert the needle into the skin if the needle is pulled out when releasing the skin. If this happens, safely throw away (dispose of) the syringe in a sharps disposal container and get a new ZILBRYSQ prefilled syringe to give the injection.

Step 10: Inject the medicine

Push the plunger head all the way down while holding onto the finger grip to inject all the medicine (Figure K).

Step 11: Release the plunger head

Slowly release the plunger head by lifting your thumb. After a complete injection, the needle guard will cover the needle and you may hear a click (Figure L).

Step 12: Throw away (dispose of) the used ZILBRYSQ prefilled syringe

Throw away (dispose of) the used ZILBRYSQ prefilled syringe into a sharps disposal container (Figure M)right away.

Do notthrow away (dispose of) the ZILBRYSQ prefilled syringe in your household trash.

If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:

• made of a heavy-duty plastic,
• can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
• upright and stable during use,
• leak-resistant, and
• properly labelled to warn of hazardous waste inside the container.

Do notthrow away (dispose of) your used sharps disposal container in your household trash unless your community guidelines permit this.

Do notrecycle your used sharps disposal container.

Always keep the sharps disposal container out of the reach of children.

Step 13: Examine the injection site

Press a cotton ball or gauze pad over the injection site and hold it for 10 seconds (Figure N).

Do notrub the injection site. You may have slight bleeding. This is normal. Apply an adhesive bandage if needed (Figure O).

The injection is complete.

For more information or help, contact your healthcare provider.

If you have any questions, call UCBCares at 1-844-599-CARE (2273) or visit www.AskUCBCares.com.

Manufactured for:
UCB, Inc.
Smyrna, GA 30080

This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Issued: 10/2023

NDC 50474-990-80
Rx only

Do not accept
if seal is missing or broken.

Lift here to open. ⇾

ZILBRYSQ ®
(zilucoplan) Injection
16.6 mg/0.416 mL
For Subcutaneous Use Only

28
Single-Dose Prefilled Syringes
Affixed with an automatic needle
protection system

This carton contains 4 individual cartons.
The entire carton is to be dispensed as one unit.

ONCE DAILY
ATTENTION PHARMACIST: Dispense the enclosed
Medication Guide to each patient.

Each individual carton contains: 7 Single-Dose
Prefilled Syringes.

NDC 50474-991-80
Rx only

Do not accept
if seal is missing or broken.

Lift here to open. ⇾

ZILBRYSQ ®
(zilucoplan) Injection
23 mg/0.574 mL
For Subcutaneous Use Only

28
Single-Dose Prefilled Syringes
Affixed with an automatic needle
protection system

This carton contains 4 individual cartons.
The entire carton is to be dispensed as one unit.

ONCE DAILY
ATTENTION PHARMACIST: Dispense the enclosed
Medication Guide to each patient.

Each individual carton contains: 7 Single-Dose
Prefilled Syringes.

NDC 50474-992-80
Rx only

Do not accept
if seal is missing or broken.

Lift here to open. ⇾

ZILBRYSQ ®
(zilucoplan) Injection
32.4 mg/0.81 mL
For Subcutaneous Use Only

28
Single-Dose Prefilled Syringes
Affixed with an automatic needle
protection system

This carton contains 4 individual cartons.
The entire carton is to be dispensed as one unit.

ONCE DAILY
ATTENTION PHARMACIST: Dispense the enclosed
Medication Guide to each patient.

Each individual carton contains: 7 Single-Dose
Prefilled Syringes.