The FDA has approved Zycubo (copper histidinate) as the first treatment for Menkes disease in pediatric patients, showing significant survival benefits when initiated early, with an established safety profile.
Written By: Pharmacally Medical News Desk
The U.S. Food and Drug Administration has approved Zycubo (copper histidinate) injection as the first FDA-approved treatment for Menkes disease in pediatric patients. The therapy is approved for children with this rare, life-threatening genetic disorder that typically presents in early infancy. Zycubo is marketed in the United States by Sentynl Therapeutics, a rare-disease focused biopharmaceutical company and a wholly owned subsidiary of Zydus Lifesciences.
About Zycubo and Its Mechanism of Action
Zycubo is an injectable formulation of copper histidinate designed to address the underlying copper deficiency that defines Menkes disease. The disorder is caused by mutations in the ATP7A gene. By delivering bioavailable copper through injection, Zycubo bypasses the defective intestinal transport pathway. This supports copper-dependent enzymatic activity essential for neurodevelopment, connective tissue formation, and cellular energy metabolism. Because neurological damage begins very early in life, treatment is intended to start as soon as possible after diagnosis, ideally within the first weeks after birth.
Clinical Trial Evidence
The FDA evaluated Zycubo (Investigational name CUTX-101) based on data from two open-label, single-arm clinical trials in pediatric patients with Menkes disease, including Study NCT04074512. Patients were treated for up to three years, with overall survival compared against contemporaneous external untreated control groups.
The analysis included 66 treated patients and 17 untreated patients, most of whom were from the United States. The results showed a clear and clinically meaningful survival benefit:
- Children who began treatment within four weeks of birth had a 78% reduction in the risk of death compared with untreated patients.
- Nearly half of early-treated patients survived beyond six years, with some living more than 12 years.
- No patients in the untreated control group survived beyond six years.
- Children who initiated treatment later than four weeks after birth also experienced a substantial survival advantage over untreated patients.
These findings underscore the critical importance of early diagnosis and prompt initiation of therapy.
Safety Profile
The safety profile of Zycubo was consistent with both the underlying disease and known effects of copper administration. The most common side effects reported included infections, respiratory problems, seizures, vomiting, fever, anemia, and injection-site reactions.
Because copper can accumulate in the body, patients receiving Zycubo should be closely monitored for signs of potential copper toxicity, with regular clinical and laboratory assessments during treatment.
Regulatory Designations Supporting Development
The Zycubo application received multiple FDA regulatory designations reflecting its potential to address a serious condition with high unmet medical need. These included Priority Review, Fast Track Designation, Breakthrough Therapy Designation, and Orphan Drug Designation.
In announcing the approval, the FDA highlighted the significant survival benefit observed in treated patients, particularly those who started therapy early in life. The agency emphasized that the decision reflects its commitment to advancing treatments for rare pediatric diseases.
FDA approval establishes standardized manufacturing and dosing requirements and enables broader access to copper histidinate beyond investigational and compassionate-use programs.
About Menkes Disease
Menkes disease is a rare inherited disorder of copper metabolism caused by mutations in the ATP7A gene which impair copper transport from the intestine into systemic circulation and critical organs, including the brain. It typically presents in early infancy and is characterized by progressive neurodegeneration, hypotonia, seizures, connective tissue abnormalities, and failure to thrive. Without treatment, the disease is usually fatal in early childhood.
References
FDA Approves First Treatment for Children with Menkes Disease, 12 January 2026, https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-children-menkes-disease
Copper Histidinate Treatment for Menkes Disease, ClinicalTrials.gov ID NCT04074512, https://www.clinicaltrials.gov/study/NCT04074512