ZYCUBO

The geometric mean (CV%) maximum serum concentration (C max ) of copper histidinate was 67 (36%) ng/mL, the geometric mean (CV%) area under the concentration-time curve from time 0 to 24 hours (AUC 0-24hr ) was 186 (21%) ng

• hr/mL, and the geometric mean (CV%) area under the concentration-time curve from time 0 to infinity (AUC 0-inf ) was 296 (15%) ng
• hr/mL following a single subcutaneous dose of 3 mg copper histidinate (approximately twice the approved recommended dose for Menkes disease patien...

The efficacy of ZYCUBO was evaluated in pediatric patients with Menkes disease (age at treatment initiation ranges 0.1 to 31.4 months) receiving 3 years of copper histidinate treatment in two open-label, single-arm clinical trials (

Trial 1NCT00001262 and

Trial 2NCT00811785). Data from ZYCUBO-treated patients in these two trials were compared to data from an untreated contemporaneous external control cohort as collected under a protocol amendment of Trial 2. In both trials, pediatric patients: Less than 1 year of age received 1.45 mg of ZYCUBO administered subcutaneously twice daily until 1...

The following clinically significant adverse reactions are described elsewhere in the labeling: Copper Accumulation and Risk of Toxicity: Drug-Induced Kidney Injury, Liver Dysfunction, Hematological Abnormalities [see Warnings and Precautions ( 5.1 )] 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,...

None. None ( 4 )

Copper Accumulation and Risk of Toxicity : Exogenous administration of copper with ZYCUBO may lead to further copper accumulation and has the potential to result in drug-induced kidney injury, liver dysfunction, and hematological abnormalities. Monitor patients during ZYCUBO treatment. Adjust dosage if necessary. ( 2.2 , 5.1 , 6.1 ) 5.1 Copper Accumulation and Risk of Toxicity Impaired copper transport in patients with Menkes disease can lead to copper accumulation and organ impairment in the ki...