FDA Approves First Treatment for Children with Menkes Disease

The U.S. Food and Drug Administration has announced the approval of Zycubo (copper histidinate) injection, marking the first treatment specifically for pediatric patients diagnosed with Menkes disease. This regulatory milestone offers a new therapeutic option for children suffering from this severe and degenerative genetic disorder.

Menkes disease is characterized by a genetic defect that prevents a child’s body from properly absorbing copper. This deficiency can lead to a range of serious health issues, including seizures, failure to thrive, developmental delays, and intellectual disabilities. The disease also affects multiple organ systems, causing abnormalities in the vascular, bladder, bowel, bone, muscle, and nervous systems. In its most common form, classical Menkes disease, symptoms typically manifest in infancy, and affected children often have a life expectancy of no more than three years. Globally, the condition affects approximately one in every 100,000 to 250,000 live births, with a higher prevalence observed in boys.

Zycubo functions as a copper replacement therapy administered via subcutaneous injection. It is designed to deliver copper in a way that circumvents the intestinal absorption defect caused by the genetic mutation, thereby enabling the body to utilize the essential mineral more effectively.

The FDA’s approval of Zycubo was based on findings from two clinical trials. These studies, which were open-label and single-arm, involved pediatric patients who received treatment for up to three years. The trials assessed overall survival by comparing the outcomes of treated patients with those of untreated patients from external control groups. The analysis encompassed 66 patients who received Zycubo and 17 who did not, with a majority of participants being from the United States.

The data from these trials indicated a significant survival benefit for early intervention. Children who began Zycubo treatment within the first four weeks of life experienced a 78% reduction in the risk of death when compared to untreated children. For this early-treated group, nearly half survived beyond six years, with some living for more than 12 years. In contrast, none of the patients in the untreated control group survived past six years. Even for children who started treatment later than four weeks after birth, a substantial improvement in survival was observed.

Common side effects associated with Zycubo included infections, respiratory issues, seizures, vomiting, fever, anemia, and reactions at the injection site. Due to the potential for copper accumulation in the body, patients receiving Zycubo require close monitoring to detect and manage any signs of toxicity.

The development and approval process for Zycubo also included designations for Priority Review, Fast Track, Breakthrough Therapy, and Orphan Drug. Sentynl Therapeutics is the company responsible for Zycubo’s development and received the FDA’s approval.

Article by Mel Anara, based upon information from the U.S. Food and Drug Administration.

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