FDA Approves Zycubo for Menkes Disease After Manufacturing Issue Resolution

The U.S. Food and Drug Administration approved Zycubo (copper histidinate) on January 13, 2026, for the treatment of Menkes disease in pediatric patients. This is the first and only treatment approved for Menkes disease, a rare and fatal genetic condition, in the United States. Zycubo is not indicated for the treatment of Occipital Horn Syndrome.

Sentynl Therapeutics Inc., a U.S.-based biopharmaceutical company wholly-owned by Zydus Lifesciences Limited, announced the approval. The company had resubmitted its New Drug Application on November 14, 2025, after receiving a complete response letter from the FDA on September 30, 2025, which cited observations regarding the manufacturing site's cGMP compliance. The CRL did not cite any other approvability concerns, nor did it identify any deficiencies in CUTX-101's efficacy and safety data.

The FDA accepted the resubmission on December 15, 2025, as a Class I response and assigned January 14, 2026 as the new PDUFA date.

The approval is supported by positive topline clinical efficacy results for Zycubo, demonstrating statistically significant improvement in overall survival for Menkes disease subjects who received early treatment with Zycubo, compared to an untreated contemporaneous external control cohort, with a nearly 80% reduction in the risk of death. Median overall survival was 177.1 months for Zycubo early treatment cohort compared to 17.6 months for the untreated contemporaneous external control cohort.

Zycubo is a subcutaneous injectable formulation of copper histidinate that restores copper homeostasis and maintains copper levels in patients with Menkes disease. The most common adverse reactions (incidence ≥7%) were pneumonia, viral infection, respiratory failure, seizure, bacterial infection, hemorrhage, hypotension, vomiting, tachycardia, pyrexia, volume depletion, fracture, dyspnea, transaminases elevation, diarrhea, fungal infection, anemia, and local administration reaction.

Menkes disease is a rare X-linked recessive pediatric disease caused by mutations of the copper transporter ATP7A encoded by the ATP7A gene. Patients with Menkes disease are born with the inability to absorb dietary copper and subsequently have impaired copper transport across the blood-brain barrier. The minimum birth prevalence for Menkes disease is believed to be 1 in 34,810 live male births, and potentially as high as 1 in 8,664 live male births, based on recent genome-based ascertainment.

The condition is characterized by distinctive clinical features, including sparse and depigmented hair ("kinky hair"), connective tissue problems, and severe neurological symptoms such as seizures, hypotonia, failure to thrive, and neurodevelopmental delays. Mortality is high in untreated Menkes disease, with many patients dying between 2-3 years of age. Most untreated patients do not survive beyond three years of age.

Acquired from Cyprium Therapeutics in 2023, Sentynl has advanced Zycubo through the final stages of development with the FDA based on positive results from pivotal studies, receiving Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and the FDA Orphan Drug Designations. Copper histidinate has also been granted Orphan Designation by the European Medicines Agency. Milder versions of ATP7A mutations are associated with conditions other than Menkes Disease, such as Occipital Horn Syndrome and ATP7A-related Distal Motor Neuropathy.