When babies are born with
Menkes disease, they need your help.
ZYCUBO® delivers
The first and only FDA-approved, bioavailable copper replacement therapy for Menkes disease, a copper deficiency caused by mutations in ATP7A.
Look for signs and symptoms of Menkes disease
What is Menkes disease?1–3
Menkes disease is a rare disorder characterized by defective copper transport and metabolism
Common signs and symptoms:
- Kinky/steely hair
- Seizures
- Hypotonia
- Feeding difficulties
- Not meeting developmental milestones
- Cephalohematomas
- Saggy facial features or loose skin on the body
- Recurrent urinary tract infections (which may be caused by bladder diverticula)
Menkes disease is an X-linked recessive disorder caused by mutations in the transport ATPase encoded by ATP7A.
Menkes disease is a rare disease, with recent estimates suggesting a prevalence of 1 in 34,810 to as high as 1 in 8664 live male births.
Patients with Menkes disease are born with the inability to absorb dietary copper and subsequently have impaired copper transport across the blood-brain barrier.
In the clinical trials, the primary efficacy analysis compared overall survival in ZYCUBO-early treatment (ET) patients with external control-early treatment (EC-ET) patients.a,b Patients treated with ZYCUBO had a statistically significant improvement in overall survival compared to the EC-ET group, with a 78% reduction in the risk of death.4
Download the ZYCUBO Lab Testing GridaZYCUBO-ET patients started within 4 weeks of birth or 4 weeks of birth corrected for prematurity (i.e., <40 weeks’ gestation) (n=31).
bEC-ET patients had no prior ZYCUBO or copper therapy, were asymptomatic for significant neurological signs and symptoms approximately 4 weeks after birth, and survived at least 4 weeks after diagnosis (n=18).
What is ZYCUBO?4
ZYCUBO is indicated for the treatment of Menkes disease and is a copper histidinate formulation to deliver elemental copper to the body via subcutaneous injection
Administering ZYCUBO
ZYCUBO is administered as a subcutaneous injection (inject directly under the skin). Your healthcare provider should show you the right way to mix and administer your child’s prescribed dose of ZYCUBO before you do this for the first time. Always follow the specific instructions given by your healthcare provider. If you have questions about preparing or giving ZYCUBO, call SentynlCares | ZYCUBO Patient Support Services at 1-888-251-2800.
How ZYCUBO is supplied
ZYCUBO comes as a powder or cake in a vial. Each vial of ZYCUBO must be mixed with sterile 0.9% sodium chloride to mix (dissolve) the powder or cake before use. Do not mix ZYCUBO with anything other than sterile 0.9% sodium chloride. Vials of ZYCUBO are for single use only. Throw the vial away after use, even if there is medicine left in the vial. Carefully remove the needle from the vial. Throw away the used needle and syringe in your sharps disposal container right away.
Storing ZYCUBO
- Store ZYCUBO in a refrigerator between 36°F to 46°F (2°C to 8°C)
- Keep ZYCUBO vials in the original carton until you are ready to use them
- Do not use ZYCUBO if the carton has been outside of the refrigerator for more than 24 hours
Efficacy of ZYCUBO4
In two open-label, single-arm clinical trials, patients treated early with ZYCUBO demonstrated statistically significant improvement in overall survival compared to the External Control Early Treatment (EC-ET)a group.
risk of death*
Primary efficacy results: Overall survival in ZYCUBO early treatment and external control early treatment cohorts with Menkes disease
| ZYCUBO-Early Treatment (n=31) | External Control-Early Treatment (n=17) | |
|---|---|---|
| Number (%) of patients alive | 16 (52%) | 2 (12%) |
| Median survival time (months) (95% CI) | 177.1 (33, NE) | 17.6 (11.5, 28.6) |
| Hazard ratio (95% CI) | 0.22 (0.10, 0.49) | |
CI=confidence interval; NE=not estimable.
Note: If death dates were unknown, patients were censored at the last known date alive.
In both the ZYCUBO Early Treatment (ZYCUBO-ET)b and ZYCUBO Late Treatment (ZYCUBO-LT)c groups, treatment was associated with an increase in survival time regardless of prematurity or ATP7A variant.†
- Primary endpoint: Overall survival compared in ZYCUBO-ET (n=31) patients vs EC-ET patients (n=17)
- Secondary endpoint: Overall survival in ZYCUBO-LT (n=35) patients vs External Control Late Treatment (EC-LT)d patients (n=16)
aEC-ET for patients with no prior ZYCUBO or copper therapy, asymptomatic for significant neurological signs and symptoms approximately 4 weeks after birth, and survived at least 4 weeks after diagnosis (n=17).
bZYCUBO-ET for patients started within 4 weeks of birth or 4 weeks of birth corrected for prematurity (i.e., <40 weeks’ gestation) (n=31).
cZYCUBO-LT for patients started after 4 weeks of birth or 4 weeks of birth corrected for prematurity (i.e., <40 weeks’ gestation) (n=35).
dEC-LT is a subset of the EC-ET cohort who were asymptomatic for significant neurological signs and symptoms approximately 4 weeks after birth, were diagnosed with Menkes disease after 4 weeks of birth, and survived at least 2 weeks after diagnosis (n=16).
*Pediatric patients from Trial 1 and Trial 2 were included in the pooled efficacy analysis if the patients carried a severe pathogenic variant of the ATP7A gene (duplication/deletion, nonsense, or a canonical splice junction variant) and were born after 1999. There are 83 pediatric patients (66 ZYCUBO; 17 EC) in this population: 21 patients (21 ZYCUBO) are from Trial 1, and 62 (45 ZYCUBO; 17 EC) are from Trial 2.
†Duplication/deletion, nonsense, or a canonical splice junction mutation.
‡CuHis-ET and CuHis-LT correspond to ZYCUBO-ET and ZYCUBO-LT patient cohorts in the clinical study.
Dosing and administration for ZYCUBO4
ZYCUBO is a copper replacement product indicated for the treatment of Menkes disease in pediatric patients
Recommended dosage and administration
| Patients Less Than 1 Year of Age | Patients 1 Year of Age to Less Than 17 Years of Age |
|---|---|
Recommended Dosage: | Recommended Dosage: |
Administration and Injection Site Recommendations:
ZYCUBO must be reconstituted prior to use. After reconstitution of ZYCUBO, the resulting concentration is 2.9 mg/mL. Inject 0.5 mL of reconstituted product to administer 1.45 mg ZYCUBO (equivalent to 0.25 mg elemental copper). Discard unused portion.
Administer ZYCUBO by subcutaneous injection at separate sites in the abdominal area (2 inches from the navel), buttocks, and the outer lateral aspect of the upper arm or thigh. Rotate injection sites with each injection to reduce the risk of lipodystrophy. Do not give injections into areas where the skin is scarred, tender, bruised, red, or hard.
Recommendations for Missed Dose:
If a ZYCUBO dose is missed, administer the missed dose as soon as possible. Administer the next scheduled dose at least 6 hours after the administration of the missed dose.
Recommended injection sites
ZYCUBO is administered subcutaneously into four main areas of the body
Download the full ZYCUBO Prescribing Information
Safety profile of ZYCUBO in clinical trials4
Adverse Reactions Occurring in ≥7% Patients With Menkes Disease (Trial 1 and Trial 2)
| Adverse Reactions | Menkes Disease (N=129) N (%) |
|---|---|
| Pneumonia | 38 (30) |
| Viral infection | 35 (27) |
| Respiratory failure1 | 30 (23) |
| Cardiopulmonary failure | 11 (9) |
| Seizure | 29 (23) |
| Bacterial infection | 26 (20) |
| Renal and urinary tract infection2 | 12 (9) |
| Hemorrhage | 23 (18) |
| Hypotension | 20 (16) |
| Vomiting | 19 (15) |
| Tachycardia | 16 (12) |
| Pyrexia | 16 (12) |
| Volume depletion | 16 (12) |
| Fracture | 16 (12) |
| Dyspnea | 16 (12) |
| Transaminases elevation | 13 (10) |
| Diarrhea | 13 (10) |
| Fungal infection | 12 (9) |
| Anemia | 11 (9) |
| Local administration reaction | 9 (7) |
Sentynl Cares is your source for helping patients access ZYCUBO
Sentynl Cares | ZYCUBO provides your patients support through the benefits verification and prescription fulfillment process
Sentynl Cares is here to help patients and caregivers receive personalized access and support. Sentynl Cares provides customized care and support for patients treated with ZYCUBO and their caregivers. A specialized ZYCUBO support team can help patients by:
Investigating insurance coverage
Assisting with financial support options
Assisting with eligibility criteria and enrollment in financial assistance programs
Connecting to a specialty pharmacy that supplies ZYCUBO
Contact Sentynl Cares | ZYCUBO
Monday through Friday, 8 AM ET–8 PM ET
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ZYCUBO resources for your patients
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Frequently Asked Questions
Dosing is based on the patient's age. Pediatric patients younger than 1 year should receive 1.45 mg subcutaneously twice daily (8–12 hours apart), while patients 1 year to less than 17 years of age should receive 1.45 mg subcutaneously once daily. ZYCUBO must be reconstituted prior to administration and is given as a subcutaneous injection. Watch ZYCUBO Dosing and Administration Video.
Before initiating therapy, obtain baseline serum copper and ceruloplasmin levels, serum electrolytes, kidney and liver function tests, and a complete blood count (CBC). During treatment, ongoing monitoring of these parameters is recommended to assess copper status and help identify potential toxicity, including renal, hepatic, or hematologic abnormalities. Download the ZYCUBO lab testing grid to see a sample testing schedule.
Patients receiving ZYCUBO should be monitored for signs of copper toxicity, including renal, hepatic, and hematologic abnormalities. Injection-site reactions may also occur. Regular laboratory monitoring is recommended throughout treatment to assess copper status and help identify potential adverse effects that may require dose modification or other clinical intervention. See Safety profile of ZYCUBO in clinical trials.
INDICATION AND USAGE
ZYCUBO is indicated for the treatment of Menkes disease in pediatric patients.
Limitations of Use
ZYCUBO is not indicated for the treatment of Occipital Horn Syndrome.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Copper Accumulation and Risk of Toxicity
Impaired copper transport in patients with Menkes disease can lead to copper accumulation and organ impairment in the kidneys, liver, and hematopoietic system. Treatment with ZYCUBO may lead to further copper accumulation and related toxicity, especially in the first two years of life given renal (kidney) and hepatic (liver) immaturity.
INDICATION AND IMPORTANT SAFETY INFORMATION
INDICATION AND USAGE
ZYCUBO is indicated for the treatment of Menkes disease in pediatric patients.
Limitations of Use
ZYCUBO is not indicated for the treatment of Occipital Horn Syndrome.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Copper Accumulation and Risk of Toxicity
Impaired copper transport in patients with Menkes disease can lead to copper accumulation and organ impairment in the kidneys, liver, and hematopoietic system. Treatment with ZYCUBO may lead to further copper accumulation and related toxicity, especially in the first two years of life given renal and hepatic immaturity.
Obtain baseline serum copper and ceruloplasmin levels, serum electrolytes, kidney and liver function, and complete blood count (CBC). After initiating ZYCUBO, monitor laboratory values every 6 weeks for the first 6 months, then every 3 months for 18 months, and then every 6 months thereafter during ZYCUBO treatment. If laboratory abnormalities are detected, consider reducing the frequency of ZYCUBO administration or temporarily withholding or permanently discontinuing ZYCUBO. Return to increased frequency of laboratory monitoring when resuming a dosage as clinically indicated.
Drug Induced Kidney Injury
Copper accumulation with ZYCUBO use has the potential to result in renal tubular toxicity in patients with Menkes disease. Routinely monitor patients starting or re-starting ZYCUBO for signs and symptoms of renal tubular toxicity. New-onset or worsening non-anion gap metabolic acidosis may be a sign of drug-related renal tubular acidosis. Increased urinary beta-2 microglobulin and/or new-onset hypophosphatemia, hyponatremia, or hypokalemia may be signs of drug-related proximal renal tubular toxicity. Provide supportive care with electrolyte repletion and supplementation as clinically indicated.
Copper accumulation with ZYCUBO use has the potential to result in glomerular injury, leading to decreased kidney function or new-onset proteinuria.
Liver Dysfunction
Copper accumulation can result in liver dysfunction. Elevations of liver transaminases have been reported in patients taking ZYCUBO for Menkes disease. Single cell necrosis, inflammation, and fibrosis, along with increased liver transaminases and bilirubin were observed in studies conducted over 13 weeks in normal juvenile rats with normal baseline copper levels.
Hematological Abnormalities
Copper accumulation with ZYCUBO can result in spleen and bone marrow dysfunction as well as interference with iron metabolism. Anemia has been reported in patients taking ZYCUBO for Menkes disease. Increased cellularity and pigmented macrophages in the spleen and increased hematological values were observed in studies conducted over 13 weeks in normal juvenile rats.
ADVERSE REACTIONS
The most common adverse reactions (≥7%) were pneumonia (30%), viral infection (27%), respiratory failure1 (23%) (including cardiopulmonary failure (9%)), seizure (23%), bacterial infection2 (20%) (including renal and urinary tract infection (9%)), hemorrhage (18%), hypotension (16%), vomiting (15%), tachycardia (12%), pyrexia (12%), volume depletion (12%), fracture (12%), dyspnea (12%), transaminases elevation (10%), diarrhea (10%), fungal infection (9%), anemia (9%), and local administration reaction (7%).
Serious adverse reactions reported in ≥5% of ZYCUBO-treated pediatric patients with Menkes disease were pneumonia, dehydration, seizure, respiratory distress, respiratory syncytial virus infection, cardiopulmonary failure, upper respiratory tract infection, respiratory failure, and vomiting.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
There are no available data on ZYCUBO use during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with ZYCUBO.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.
Lactation
Risk Summary
There are no data on the presence of ZYCUBO in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZYCUBO and any potential adverse effects on the breastfed infant from ZYCUBO or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of ZYCUBO for the treatment of Menkes disease have been established in pediatric patients and are supported by evidence from two clinical trials. Data from patients in these two trials were compared to data from an untreated contemporaneous external control cohort.
Geriatric Use
Menkes disease is a disease of pediatric patients. Clinical trials of ZYCUBO did not include patients 65 years of age and older.
You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Please see full Prescribing Information for ZYCUBO.
1Respiratory failure consists of multiple similar terms including cardiopulmonary failure.
2Bacterial infection consists of multiple similar terms including renal and urinary tract infection.
References: 1. Ojha R, Prasad AN. Menkes disease: what a multidisciplinary approach can do. J Multidiscip Healthc. 2016;9:371-385. 2. Kaler SG. ATP7A-related copper transport diseases—emerging concepts and future trends. Nat Rev Neurol. 2011;7(1):15-29. 3. Kaler SG, Ferreira CR, Yam LS. Estimated birth prevalence of Menkes disease and ATP7A-related disorders based on the Genome Aggregation Database (gnomAD). Mol Genet Metab Rep. 2020;24:100602. 4. ZYCUBO. Prescribing information. Sentynl Therapeutics; 2026.
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