FDA Approves First Treatment for Children With Menkes Disease
The U.S. Food and Drug Administration has approved the Zycubo (copper histidinate) injection as the first treatment for Menkes disease in pediatric patients.
“With today’s action, children with this devastating, degenerative disease will have an FDA-approved treatment option and the potential to live longer,” said Christine Nguyen, M.D., Deputy Director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine in the FDA’s Center for Drug Evaluation and Research. “The FDA will continue to work with the rare disease community to advance drug development for patients with Menkes disease and other rare conditions.”
Menkes disease is a neurodegenerative disorder caused by a genetic defect that impairs a child’s ability to absorb copper. The disease is characterized by seizures, failure to gain weight and grow, developmental delays, and intellectual disability. It leads to abnormalities of the vascular system, bladder, bowel, bones, muscles, and nervous system. Children with classical Menkes (90% of those with the disease) begin to develop symptoms in infancy and typically do not live past three years. It affects approximately one in every 100,000-250,000 live births worldwide and is more common in boys.
Zycubo is a copper replacement therapy given by subcutaneous injection. It delivers copper in a form that bypasses the genetic defect in intestinal absorption, allowing the body to better use the mineral.
The FDA evaluated Zycubo in two open-label, single-arm clinical trials in pediatric patients treated for up to three years. Overall survival was assessed by comparing treated patients to untreated patients from contemporaneous external control groups. The analysis included 66 treated patients and 17 untreated patients, most of whom were from the United States.
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, and some survived more than 12 years. No patients in the untreated control group survived beyond six years. Children who started treatment later than four weeks after birth also experienced a substantial survival benefit.
The most common side effects reported with Zycubo 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 potential toxicity.
“This approval marks an unprecedented advance for children with Menkes disease,” said Tracy Beth Hoeg, M.D., Ph.D., Acting Director of 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.”
This application received Priority Review, Fast Track Designation, Breakthrough Therapy Designation, and Orphan Drug Designation. The FDA approved Zycubo for Sentynl Therapeutics.
