Drug Trials Snapshots: ZYCUBO
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the ZYCUBO Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
ZYCUBO (copper histidinate)
(Zye kyoo’ boe)
Sentynl Therapeutics Inc.
Approval date: January 12, 2026
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ZYCUBO is a copper replacement therapy that is used for the treatment of Menkes disease in pediatric patients. ZYCUBO is not to be used for the treatment of Occipital Horn Syndrome.
How is this drug used?
ZYCUBO is given by subcutaneous injection two times a day for patients younger than 1 year of age and once a day for patients 1 year of age to younger than 17 years of age.
Who participated in the clinical trials?
The FDA approved ZYCUBO based on evidence from two clinical trials (Trial 1 and Trial 2), in which efficacy and safety were evaluated in 66 and 129 ZYCUBO-treated pediatric patients with Menkes disease, respectively. The trials were conducted at a single site in the United States.
How were the trials designed?
ZYCUBO was evaluated in 129 pediatric patients with Menkes disease receiving three years of ZYCUBO treatment in two open-label, single-arm clinical trials (Trial 1, NCT00001262 and Trial 2, NCT00811785). Survival data from ZYCUBO-treated patients in these two trials were compared to survival data from an untreated contemporaneous external control cohort as collected under a protocol amendment of Trial 2. In both trials, patients younger than 1 year of age received 1.45 mg of ZYCUBO given subcutaneously twice a day until 1 year of age; patients 1 year of age and older received 1.45 mg of ZYCUBO subcutaneously once daily for up to three years.
Overall survival was evaluated in a subset of the pooled population from Trial 1 and Trial 2, referred to as the pooled primary efficacy population. This efficacy population included only patients with Menkes disease who carried a severe pathogenic variant of the ATP7A gene and were born after 1999. There were 83 pediatric patients (66 ZYCUBO; 17 external control) in this pooled primary efficacy population: 21 patients (21 ZYCUBO) from Trial 1 and 62 patients (45 ZYCUBO; 17 external control) from Trial 2.
Safety data were evaluated in 129 patients receiving ZYCUBO in Trial 1 and Trial 2. There were insufficient safety data in the control group for evaluation.
DEMOGRAPHICS SNAPSHOT
Figure 1 and Figure 2 summarize how many males and females were enrolled in the combined clinical trials used to evaluate the efficacy of ZYCUBO.
Figure 1. Baseline Demographics by Sex, Primary Efficacy Population, ZYCUBO Early Treatment Group
Source: Adapted from FDA Review
Note: ZYCUBO Early Treatment Group includes patients who started ZYCUBO treatment within four weeks of birth
Figure 2. Baseline Demographics by Sex, Primary Efficacy Population, ZYCUBO Late Treatment Group
Source: Adapted from FDA Review
Note: ZYCUBO Late Treatment Group includes patients who started ZYCUBO treatment after four weeks of birth
Figure 3 summarizes how many patients by sex were in the combined clinical trials used to evaluate the side effects of ZYCUBO.
Figure 3. Baseline Demographics by Sex, Safety Population
Source: Adapted from FDA Review
Figure 4 and Figure 5 summarize the percentage of patients by race/ethnicity enrolled in the combined clinical trials used to evaluate the efficacy of ZYCUBO.
Figure 4. Baseline Demographics by Race/Ethnicity, Primary Efficacy Population, ZYCUBO Early Treatment Group
Source: Adapted from FDA Review
Note: ZYCUBO Early Treatment Group includes patients who started ZYCUBO treatment within four weeks of birth
Figure 5. Baseline Demographics by Race/Ethnicity, Primary Efficacy Population, ZYCUBO Late Treatment Group
Source: Adapted from FDA Review
Note: ZYCUBO Late Treatment Group includes patients who started ZYCUBO treatment after four weeks of birth
Figure 6 summarizes how many patients by race/ethnicity were in the combined trials used to evaluate the side effects of ZYCUBO.
Figure 6. Baseline Demographics by Race/Ethnicity, Safety Population
Source: Adapted from FDA Review
Figure 7 and Figure 8 summarize the percentage of patients by age at treatment start in the combined clinical trials used to evaluate the efficacy of ZYCUBO.
Figure 7. Baseline Demographics by Age at Treatment Start, Primary Efficacy Population, ZYCUBO Early Treatment Group
Source: Adapted from FDA Review
Note: ZYCUBO Early Treatment Group includes patients who started ZYCUBO treatment within four weeks of birth
Figure 8. Baseline Demographics by Age at Treatment Start, Primary Efficacy Population, ZYCUBO Late Treatment Group
Source: Adapted from FDA Review
Note: ZYCUBO Late Treatment Group includes patients who started ZYCUBO treatment after four weeks of birth
Figure 9 summarizes how many patients by age were in the combined trials used to evaluate the side effects of ZYCUBO.
Figure 9. Baseline Demographics by Age at Treatment Start, Safety Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1 summarizes patient demographic by age, sex, and race/ethnicity in the Primacy Efficacy Population and the Safety Population.
Table 1. Baseline Demographics, Primary Efficacy and Safety Populations
| Demographic | Primary Efficacy Population | Safety Population N=129 | |||
|---|---|---|---|---|---|
| ZYCUBO-ET N=31 | HC-ET N=17 | ZYCUBO-LT N=35 | HC-LT N=16 | ||
| Age1, months | |||||
| Mean (SD) | 0.7 (0.6) | NA | 8.0 (6.5) | NA | 6.1 (7.9) |
| Median (range) | 0.4 (0.1, 1.9) | NA | 7.1 (1.3, 31.4) | NA | 3.8 (0, 48.3) |
| Sex, n (%) | |||||
| Female | 0 (0.0) | 0 (0.0) | 2 (5.7) | 0 (0.0) | 2 (1.6) |
| Male | 31 (100.0) | 17 (100.0) | 33 (94.3) | 16 (100.0) | 127 (98.4) |
| Race/ethnicity, n (%) | |||||
| Asian/Pacific Islander | 0 (0.0) | 0 (0.0) | 2 (5.7) | 0 (0.0) | 6 (4.7) |
| Black | 5 (16.1) | 1 (5.9) | 2 (5.7) | 1 (6.2) | 15 (11.6) |
| Hispanic | 6 (19.4) | 1 (5.9) | 4 (11.4) | 1 (6.2) | 15 (11.6) |
| Other | 0 (0.0) | 1 (5.9) | 3 (8.6) | 1 (6.2) | 9 (7.0) |
| Unknown | 2 (6.5) | 0 (0.0) | 4 (11.4) | 0 (0.0) | 14 (10.9) |
| White | 18 (58.1) | 14 (82.4) | 20 (57.1) | 13 (81.2) | 70 (54.3) |
Source: Adapted from FDA Review
1 Age at treatment start for Primary Efficacy Population
ET = ZYCUBO treatment started within four weeks of birth
LT = ZYCUBO treatment started after four weeks of birth
Abbreviations: ET, early treatment; HC, historical control; LT, late treatment; SD, standard deviation
What are the benefits of this drug?
Compared with patients who did not receive ZYCUBO treatment (control), ZYCUBO improved the overall survival in patients who started and received ZYCUBO treatment within four weeks of birth for a total of three years (ZYCUBO Early Treatment; Table 2 and Figure 10). Fifteen (48%) patients survived >6 years, including 7 (23%) patients who survived >12 years. No control patients survived >6 years.
ZYCUBO also improved the overall survival in patients who started and received ZYCUBO treatment after four weeks of birth for a total of three years (ZYCUBO Late Treatment; Table 3 and Figure 11). Eleven (31.4%) patients survived >6 years, including 1 patient (2.9%) who survived >12 years. No control patients survived >6 years.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Primary Efficacy Results: Overall Survival in ZYCUBO Early Treatment and External Control Early Treatment Cohorts With Menkes Disease
| Parameter | 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) | |
Source: ZYCUBO Prescribing Information
Note: If death dates were unknown, patients were censored at the last known date alive.
Abbreviations: CI, confidence interval; NE, not estimable
Figure 10. Kaplan-Meier Overall Survival Curve for the ZYCUBO Early Treatment and External Control Early Treatment Cohorts With Menkes Disease
Source: ZYCUBO Prescribing Information
Table 3. Secondary Efficacy Results: Overall Survival in ZYCUBO Late Treatment and External Control Late Treatment Cohorts with Menkes Disease
| Parameter | ZYCUBO Late Treatment N=35 | External Control Late Treatment N=16 |
|---|---|---|
| Number (%) of patients alive | 12 (34) | 2 (12) |
| Median survival time, months (95% CI) | 62.4 (29.6, 80.7) | 20.7 (12.6, 28.6) |
| Hazard ratio (95% CI) | 0.27 (0.12, 0.57) | |
Source: ZYCUBO Prescribing Information
Note: If death dates were unknown, patients were censored at the last known date alive.
Abbreviations: CI, confidence interval
Figure 11. Kaplan-Meier Overall Survival Curve for ZYCUBO Late Treatment and External Control Late Treatment Cohorts With Menkes Disease
Source: ZYCUBO Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: The number of female patients was small; therefore, differences in how ZYCUBO worked between males and females could not be determined.
- Race: The number of patients of races other than White was small; therefore, differences in how ZYCUBO worked among races could not be determined.
- Age: The age range of patients was narrow (0 to 31 months); therefore, differences in how ZYCUBO worked among age groups could not be determined.
What are the possible side effects?
Treatment with ZYCUBO may lead to excessive copper in the body and has the potential to result in injury to the kidney, liver, and blood-producing system. The most common side effects of ZYCUBO occurring in ≥15% patients include bacterial and viral infections, seizure, excessive bleeding, low blood pressure, vomiting, and a condition where the respiratory system fails in its gas exchange function.
What are the possible side effects (results of trials used to assess safety)?
Table 4 summarizes the adverse reaction occurring in ≥7% patients with Menkes disease in Trial 1 and Trial 2.
Table 4. Adverse Reactions Occurring in ≥7% Patients With Menkes Disease, Safety Population, Trial 1 and Trial 2
| Adverse Reaction | 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) |
Source: ZYCUBO Prescribing Information
1 Respiratory failure consists of multiple similar terms including cardiopulmonary failure.
2 Bacterial infection consists of multiple similar terms including renal and urinary tract infection.
Were there any differences in side effects among sex, race and age?
- Sex: The number of female patients was small; therefore, differences in the occurrence of side effects between males and females could not be determined
- Race: The number of patients treated was small; therefore, differences in the occurrence of side effects among races could not be determined reliably.
- Age: The age range of patients was narrow; therefore, differences in occurrence of side effects among age groups could not be determined.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.