FDA approves Zycubo for treatment of Menkes disease in children

The FDA has approved the Zycubo (copper histidinate; Sentynl Therapeutics Inc) injection to manage Menkes disease in children on January 12, 2025.¹

This approval follows 2 open-label, single-arm clinical trials evaluating overall survival in patients receiving Zycubo. These individuals were compared to an untreated population, with 66 individuals in the treated group and 17 in the untreated group. The odds of death were reduced by 78% in the former group vs the latter.¹

“This approval marks an unprecedented advance for children with Menkes disease,” said Tracy Beth Hoeg, MD, PhD, acting director of the Center for Drug Evaluation and Research (CDER). “The company demonstrated a large improvement in overall survival compared with untreated patients, using an innovative trial design that addressed the challenges of studying an ultra-rare disease.”¹

Long-term survival benefits

Additional outcomes observed in the trial include survival beyond 6 years in nearly half of treated patients. In comparison, the rate of 6-year survival in the untreated group was 0%. Survival was significantly improved in patients starting treatment both before and after the 4-week threshold after birth.¹

Patients receiving Zycubo had a median overall survival of 177.1 months vs 17.6 months among untreated controls.² Alongside the FDA approval, this treatment has been granted Orphan Designation by the European Medicines Agency.

Side effects in patients receiving Zycubo included seizures, respiratory problems, infections, fever, anemia, vomiting, and injection site reactions.¹ Experts also warned that patients receiving Zycubo should be closely monitored, since copper can accumulate in the body.

The copper replacement therapy is administered through a subcutaneous injection. This allows copper to be delivered while bypassing the genetic defect in intestinal absorption. Through this method, the body may better use the mineral.¹

Overview of Menkes disease and epidemiology

Approximately 1 in every 100,000 to 250,000 live births worldwide are impacted by Menkes disease, defined as a neurodegenerative disorder caused by a genetic defect adversely impacting a child’s ability to absorb copper. Symptoms include developmental delay, seizures, failure to gain weight, and intellectual disability.¹

Increased rates of Menkes disease have also been observed in male patients vs female patients, with a rate up to 1 in 8664 live births.² Gene mutations of the copper transporter ATP7A have been linked to the condition, with milder mutations of ATP7A linked to other conditions such as Occipital Horn Syndrome and ATP7A-related Distal Motor Neuropathy.

Patients with Menkes disease may experience abnormalities in the nervous system, vascular system, bowel, bladder, muscles, and bones.¹ Symptoms often develop in infancy, and survival is not common past 3 years. According to Christine Nguyen, MD, deputy director in the CDER, the approval of Zycubo provides children with an option that may allow them to live longer.

"Increased awareness of Menkes disease and rapid testing upon suspicion are critical, as beginning copper histidinate therapy in affected neonates has been shown to reduce symptoms and prolong life,” said Stephen Kaler, MD, a clinical genetics and genomics specialist at the Columbia University Medical Center.²

References

1. FDA approves first treatment for children with Menkes disease. US Food and Drug Administration. January 12, 2026. Accessed January 13, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-children-menkes-disease
2. Sentynl Therapeutics Inc. announces FDA approval of ZYCUBO® (copper histidinate). Sentynl Therapeutics. January 13, 2026. Accessed January 13, 2026. https://www.prnewswire.com/news-releases/sentynl-therapeutics-inc-announces-fda-approval-of-zycubo-copper-histidinate-302659637.html