Zilbrysq Drug Information
Generic name: ZILUCOPLAN
Complement Inhibitor [EPC]
Uses of Zilbrysq
is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. ZILBRYSQ is a complement inhibitor indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.
Dosage & Administration of Zilbrysq
| Less than 56 kg | 16.6 mg |
|---|---|
| 56 kg to less than 77 kg | 23 mg |
| 77 kg and above | 32.4 mg |
Side Effects of Zilbrysq
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. Of these, 137 patients were exposed for at least 6 months, and 87 were exposed for at least 1 year. In a placebo-controlled study (Study 1) in patients with gMG, 86 patients received ZILBRYSQ 0.3 mg/kg . Of these 86 patients, approximately 61% were female, 77% were White, 8% were Asian, and 8% were of Hispanic or Latino ethnicity.
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 Adverse Reaction ZILBRYSQ 0.3 mg/kg (n=86) % Placebo (n=88) % Injection site reactions 29 16 Upper respiratory tract infections 14 7 Diarrhea 11 2 Urinary tract infection 8 5 Nausea or vomiting 8 7 Lipase increased 7 0 Amylase increased 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.
Warnings & Cautions for Zilbrysq
Serious Meningococcal Infections
ZILBRYSQ, a complement inhibitor, increases a patient's susceptibility to serious, life-threatening, or fatal infections caused by meningococcal bacteria (septicemia and/or meningitis) in any serogroup, including non-groupable strains. Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of ZILBRYSQ treatment is contraindicated in patients with unresolved serious Neisseria meningitidis infection.
Complete or update meningococcal vaccination (for serogroups A, C, W, Y and B) at least 2 weeks prior to administration of the first dose of ZILBRYSQ, according to current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of ZILBRYSQ therapy. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information.
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 meningococcal vaccines as soon as possible. Various durations and regimens of antibacterial drug prophylaxis have been considered, but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors, including ZILBRYSQ. The benefits and risks of treatment with ZILBRYSQ, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by Neisseria meningitidis. Vaccination does not eliminate the risk of meningococcal infections, despite development of antibodies following vaccination.
Closely monitor patients 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. Promptly treat known infections.
Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of ZILBRYSQ in patients who are undergoing treatment for serious meningococcal infection, depending on the risks of interrupting treatment in the disease being treated . ZILBRYSQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) .
ZILBRYSQ
REMS ZILBRYSQ is available only through a restricted program under a REMS called ZILBRYSQ REMS, because of the risk of serious meningococcal infections . Notable requirements of the ZILBRYSQ REMS include the following: Prescribers must enroll in the REMS. Prescribers must counsel patients about the risk of serious meningococcal infection. Prescribers must provide the patients with the REMS educational materials. Prescribers must assess patient vaccination status for meningococcal vaccines (against serogroups A, C, W, Y, and B) and vaccinate if needed according to current ACIP recommendations two weeks prior to the first dose of ZILBRYSQ. Prescribers must provide a prescription for antibacterial drug prophylaxis if treatment must be started urgently and the patient is not up to date with meningococcal vaccines according to current ACIP recommendations at least two weeks prior to the first dose of ZILBRYSQ. Pharmacies that dispense ZILBRYSQ must be certified in the REMS and must verify prescribers are certified.
Patients must receive counseling from the prescriber about the need to receive meningococcal vaccines per ACIP recommendations, the need to take antibiotics as directed by the prescriber, and the signs and symptoms of meningococcal infection. Patients must be instructed to carry the Patient Safety Card with them at all times during and for 2 months following treatment discontinuation with ZILBRYSQ. Further information is available at www.ZILBRYSQREMS.com or 1-877-414-8353.
Other Infections Serious infections with Neisseria species (other than Neisseria meningitidis )
including disseminated gonococcal infections, have been reported in patients treated with complement inhibitors. ZILBRYSQ blocks terminal complement activation; therefore, patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Administer vaccinations for the prevention of Streptococcus pneumoniae infection according to ACIP recommendations.
Patients receiving ZILBRYSQ are at increased risk for infections due to these organisms, even if they develop antibodies following vaccination.
Pancreatitis and Other Pancreatic Conditions Pancreatitis and pancreatic cysts have been reported
in patients treated with ZILBRYSQ. During the open-label extension studies, seven (3.3%) patients experienced pancreatic events, including 4 (1.9%) patients with pancreatitis and 3 (1.4%) with pancreatic cysts. In the 3-month, double-blind Study 1, adverse reactions of increased lipase were reported in six (6.9%) patients treated with ZILBRYSQ compared to no patients on placebo, and adverse reactions of increased amylase were reported in four (4.7%) patients treated with ZILBRYSQ compared to one (1.1%) patient on placebo. Lipase levels exceeded three times the upper limit of normal in six (7%) patients after being started on ZILBRYSQ compared to no patients on placebo.
Patients should be informed of this risk before starting ZILBRYSQ. Obtain lipase and amylase levels at baseline before starting treatment with ZILBRYSQ. Discontinue ZILBRYSQ in patients with suspected pancreatitis and initiate appropriate management until pancreatitis is ruled out or has resolved.
Pregnancy Safety for Zilbrysq
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 2% to 4% and 15% to 20%, respectively.
Data Animal Data Subcutaneous administration of zilucoplan (0, 1, 2, or 4 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 of Zilbrysq
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Contraindications for Zilbrysq
is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection . ZILBRYSQ is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection.
Clinical Studies of Zilbrysq
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). Table 3: Change from Baseline in MG-ADL and QMG Total Scores at Week 12 in Adult Patients with gMG who are Anti-AChR Antibody Positive (Study 1) Efficacy Endpoints: LS Mean (95% CI) ZILBRYSQ (n = 86) Placebo (n = 88) ZILBRYSQ change LS mean difference vs. placebo (95% CI) p-value* Abbreviations: CI = confidence interval; MG-ADL, myasthenia gravis activities of daily living scale; QMG, quantitative myasthenia gravis; LS = least square MG-ADL Total Score -4.39 (-5.28, -3.50) -2.30 (-3.17, -1.43) -2.09 (-3.24, -0.95) < 0.001 QMG Total Score -6.19 (-7.29, -5.08) -3.25 (-4.32, -2.17) -2.94 (-4.39, -1.49) < 0.001 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. Figure 1
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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