zilucoplan (Rx)

>10%

Injection site reactions (29%)

Upper respiratory tract infections (14%)

Diarrhea (11%)

1-10%

Urinary tract infection (8%)

Nausea/vomiting (8%)

Lipase increased (7%)

Amylase increased (5%)

Frequency Not Defined

Pancreatitis

Pancreatic cysts

Transient elevated blood eosinophils

Contraindications

Unresolved Neisseria meningitidis infection

Cautions

Serious meningococcal infections

• Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors
• Zilucoplan increases susceptibility to serious and life-threatening meningococcal infections (septicemia and/or meningitis) caused by any serogroup, including non-groupable strains
• Closely monitor for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected
• Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur
• Withhold zilucoplan in patients who are undergoing treatment for meningococcal infection until infection resolved

• Meningococcal vaccination

  • Complete or update meningococcal vaccination (for both serogroups A, C, W, and Y [MenACWY] and serogroup B [MenB]) at least 2 weeks before administering the first dose, according to current ACIP recommendations for meningococcal vaccinations in patients receiving a complement inhibitor
  • Revaccinate in accordance with ACIP recommendations considering the duration of zilucoplan therapy
  • Note: ACIP recommends administration schedule for patients receiving complement inhibitors that differs from prescribing information

• Urgent therapy

  • If urgent therapy is indicated in a patient who is not current with both MenACWY and MenB vaccines, administer meningococcal vaccine(s) as soon as possible and provide antibacterial drug prophylaxis
  • Various durations and regimens of antibacterial drug prophylaxis have been considered, but optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors
  • Assess benefits and risks of treatment and the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, compared with the known risks for meningococcal infection

Zilbrysq REMS

• Available only through a restricted program, because of risk of meningococcal infections

• REMS requirements

  • Prescribers must enroll in the REMS
  • Prescribers must counsel patients about risk of meningococcal infection
  • Prescribers must provide patients with REMS educational materials
  • Prescribers must assess patient vaccination status for both meningococcal vaccines (MenACWY and MenB) and vaccinate if needed according to current ACIP recommendations for meningococcal vaccinations in patients receiving a complement inhibitor 2 weeks before first dose
  • Prescribers must provide a prescription for antibacterial drug prophylaxis if treatment must be started urgently, and patient is not up to date with both MenACWY and MenB vaccines
  • Pharmacies that dispense zilucoplan must be certified in the REMS and must verify prescribers are certified
  • Patients must receive counseling from prescriber about the need to receive both meningococcal vaccines (MenACWY and MenB) per ACIP recommendations, the need to take antibiotics as directed, and the signs and symptoms of meningococcal infection
  • Instruct patients to always carry the Patient Safety Card with them during and for 2 months following treatment discontinuation
  • Further information is available at www.ZILBRYSQREMS.com or 1-877-414-8353

Other infections

• Blocks terminal complement activation; therefore, patients may have increased susceptibility to infections, especially with encapsulated bacteria (eg, N meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, N gonorrhoeae); counsel patients about gonorrhea prevention and advise regular testing if at risk
• Administer vaccinations for prevention of S pneumoniae and H influenzae type b (Hib) infections according to ACIP guidelines
• Persons receiving zilucoplan are at increased risk for infections due to these bacteria, even after vaccination

Pancreatitis and other pancreatic conditions

• Pancreatitis and pancreatic cysts reported
• Obtain lipase and amylase levels at baseline before initiating treatment
• Discontinue with suspected pancreatitis and initiate appropriate management until pancreatitis is ruled out or has resolved
• Inform patients that persistent abdominal pain, sometimes severe or radiating to the back, which may or may not be accompanied by vomiting, is a hallmark symptom of acute pancreatitis; instruct patients to contact healthcare provider if symptoms occur to determine if therapy should be discontinued

Pregnancy

Human data are not available regarding use in pregnant females to evaluate for drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

Animal data

• Administration to pregnant monkeys resulted in increases in embryofetal death at maternal exposures similar to those in humans at therapeutic doses
• A no-effect dose for adverse developmental effects in monkeys was not identified
• 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

Lactation

Data are not available regarding presence of zilucoplan in human milk, effects on breastfed infants, or effects on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Binds to complement protein C5 and inhibits its cleavage to C5a and C5b, preventing the generation of the terminal complement complex, C5b-9

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

Absorption

Peak plasma concentration: 3-6 hr

Steady-state trough concentration reach by 4-12 weeks

Distribution

Protein bound: >99%

Vd: 3.51 L

Metabolism

Zilucoplan is a peptide and expected to be degraded into small peptides and amino acids via catabolic pathways

Elimination

Half-life: ~172 hr (7-8 days)

SC Preparation

Visually inspect for particulate matter and discoloration

Solution should appear clear to slightly opalescent, colorless

Discard if solution contains visible particles, is cloudy, or if foreign particulate matter is present

Does not contain preservatives; discard unused portions of drug remaining in syringe

If stored refrigerated

• Before injecting, remove 1 prefilled syringe from refrigerator and place on clean, flat surface
• Allow syringe to reach room temperature out of direct sunlight (30-45 minutes)
• Do not heat or place in microwave
• Immediately return carton with other syringes to refrigerator

If stored at room temperature

• Remove 1 prefilled syringe from carton
• Do not return syringe to refrigerator after it has been stored at room temperature

SC Administration

Intended for use under the guidance and supervision of a healthcare professional

Patients (or caregivers) may administer after training in SC injection technique

Inject full content of single-dose prefilled syringe at ~same time each day

Administer SC into areas of abdomen, thighs, or back of 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

Missed dose

• Administer as soon as possible
• Thereafter, resume dosing at regular scheduled time
• Do not administer >1 dose/day

Storage

Store in original carton

Pharmacy prior to dispensing

• Refrigerate at 2-8ºC (36-46ºF)
• Do not freeze

After dispensing

• Refrigeration

  • 2-8ºC (36-46ºF)
  • Until expiration date on carton

• Room temperature

  • Up to 30ºC (86ºF)
  • May keep at room temperature up to 3 months after removing from refrigerator or until expiration date on the carton, whichever occurs first
  • Do not return to refrigerator after it has been stored at room temperature