ZILBRYSQ Dosage & Rx Info | Uses, Side Effects

Zilbrysq Generic Name & Formulations

Legal Class

General Description

Zilucoplan (as sodium) 16.6mg/0.416mL, 23mg/0.574mL, 32.4mg/0.81mL; soln for SC inj; preservative-free.

Pharmacological Class

Complement inhibitor.

How Supplied

Single-dose prefilled syringes–28 (4 cartons x 7 syringes each)

Storage

Store Zilbrysq prefilled syringes refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton until dispensing. Do not freeze.

Zilbrysq prefilled syringes may be stored at room refrigerator up to 30°C (86°F) for a single period of up to 3 months or until expiration date on the carton, whichever occurs first.

Manufacturer

UCB Inc.

Generic Availability

Mechanism of Action

The precise mechanism by which zilucoplan exerts its therapeutic effect in generalized myasthenia gravis is unknown but is presumed to inhibit complement protein C5 cleavage to C5a and C5b, reducing the C5b-9 deposition at the neuromuscular junction.

Zilbrysq Indications

Indications

Generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody positive.

Zilbrysq Dosage and Administration

Prior to Treatment Evaluations

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, administer meningococcal vaccine(s) as soon as possible and give antibacterial drug prophylaxis.

Obtain baseline lipase and amylase levels prior to initiation.

Adult

Give by SC inj into the back of the upper arms, thighs, or abdomen; rotate inj sites. <56kg: 16.6mg once daily; 56–<77kg: 23mg once daily; ≥77kg: 32.4mg once daily.

Children

Not established.

Administration

Intended for use under the supervision of a health care professional. May self-inject Zilbrysq after proper training.

Give 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. Injection into the upper, outer arm should be done by a caregiver.

Administer Zilbrysq at approximately the same time each day.

Zilbrysq Contraindications

Contraindications

Unresolved Neisseria meningitidis infection.

Zilbrysq Boxed Warnings

Boxed Warning

Serious meningococcal infections.

Zilbrysq Warnings/Precautions

Warnings/Precautions

Increased risk for serious meningococcal infections (septicemia and/or meningitis). Vaccinate or revaccinate for meningococcal disease according to ACIP guidelines at least 2 weeks prior to treatment. Monitor closely for signs of meningococcal infection; evaluate immediately if infection is suspected. Discontinue zilucoplan if undergoing treatment for meningococcal infection. Risk for other infections (eg, due to N. species [including disseminated gonococcal infections], S. pneumoniae, H. influenza); give prophylactic vaccinations accordingly. Pancreatitis and other pancreatic conditions. Obtain baseline lipase and amylase levels prior to initiation. Discontinue if pancreatitis is suspected; manage appropriately until ruled out or resolved. Pregnancy. Nursing mothers.

Pregnancy Considerations

Risk Summary

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 embryo-fetal death at maternal exposures similar to those in humans.

Nursing Mother Considerations

Risk Summary

No data on the presence of zilucoplan in human milk, the effects on the breastfed infant, or the effects on milk production.
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Zilbrysq and any potential adverse effects on the breastfed infant from Zilbrysq or from the underlying maternal condition.

Pediatric Considerations

Safety and efficacy have not been established.

REMS

YES

Zilbrysq Pharmacokinetics

Absorption

Peak plasma concentration: 3–6 hours (post-dose).

Distribution

Mean volume of distribution at steady state: 3.51 L. Plasma protein bound: >99%.

Metabolism

Catabolic pathways.

Elimination

Renal, fecal: negligible (<1% of the dose). Half-life: ~172 hours (7–8 days).

Zilbrysq Interactions

Not Applicable

Zilbrysq Adverse Reactions

Adverse Reactions

Inj site reactions, upper respiratory tract infection, diarrhea; meningococcal infection (may be fatal), pancreatic events.

Zilbrysq Clinical Trials

Clinical Trials

The approval was based on data from the double-blind, placebo-controlled phase 3 RAISE study (ClinicalTrials.gov Identifier: NCT04115293), which included 174 adults with mild to severe anti-AChR-antibody positive gMG. Study participants (mean age, 53 years) were randomly assigned 1:1 to receive zilucoplan (n=86) or placebo (n=88) subcutaneously once daily for 12 weeks.

The primary endpoint was the change from baseline to week 12 in the MG-Activities of Daily Living (MG-ADL) total score, which assesses the impact of gMG on daily functions of 8 signs/symptoms typically affected in gMG. At baseline, the mean MG-ADL total score was 10.6 (range: 6-19). Efficacy was also measured using the Quantitative Myasthenia Gravis (QMG) total score, which assesses muscle weakness. For both measures, higher scores indicate more impairment.

Treatment with zilucoplan was associated with statistically significant improvements in both MG-ADL total score (difference from placebo, -2.09 [95% CI, -3.24, -0.95]) and QMG total score (difference from placebo, -2.94 [95% CI, -4.39, -1.49]) (both P <.001). Additionally, the proportion of patients with improvements of at least 3 and 5 points in the MG-ADL total score and QMG total score, respectively, was greater for zilucoplan (73.1% and 58%) compared with placebo (46.1% and 33%).

Zilbrysq Note