The FDA has approved copper histidinate (Zycubo, Sentynl Therapeutics) injection as the first and only treatment to date, for Menkes disease in pediatric patients, the agency announced. The treatment was previously known as CUTX-101.

Menkes is a rare neurodegenerative disorder associated with the inability to absorb copper and, when untreated, has a high mortality rate — especially before the age of 3 years.

“Children with this devastating, degenerative disease will have an FDA-approved treatment option and the potential to live longer,” Christine Nguyen, MD, deputy director of the Office of Rare Diseases, Pediatrics, Urologic, and Reproductive Medicine in the FDA’s Center for Drug Evaluation and Research (CDER), said in a release.

The approval was based on the pooled analysis of two open-label trials that assessed survival between patients treated with vs without copper histidinate. The group that started treatment within 4 weeks of birth and continued treatment for up to 3 years had a 78% reduced risk for death compared with the untreated control group; nearly half survived beyond 6 years vs none of the untreated participants, and some survived beyond 12 years.

A substantial survival benefit was also found for participants who began receiving the treatment more than 4 weeks after birth. 

The most commonly reported adverse events for the treatment included respiratory problems, infections, seizures, vomiting, fever, anemia, and injection site reactions. The FDA added in its release that “because copper can accumulate in the body, patients receiving Zycubo should be closely monitored for potential toxicity.”

‘Unprecedented Advance’

Menkes disease is caused by mutations in ATP7A and most commonly affects boys. It is associated with severe neurological symptoms, such as seizures, poor muscle tone (hypotonia), and neurodevelopmental delays.

The disease is estimated to affect about 1 in 100,000-250,000 live births, the FDA noted, with untreated patients often dying between the ages of 2 and 3 years.

The new treatment is a bioavailable copper replacement therapy in the form of a subcutaneous injectable to be given daily. 

After initially granting priority review, the FDA set the original Prescription Drug User Fee Act (PDUFA) date for last year. However, the agency sent the manufacturer a complete response letter in October due to a manufacturing issue and the company submitted a revised New Drug Application in November. Although a new PDUFA date was set for January 14, the FDA gave its approval 2 days earlier than expected. 

“This approval marks an unprecedented advance for children with Menkes disease,” Tracy Beth Hoeg, MD, PhD, acting director of CDER, said in the FDA’s release. 

Occipital Horn Syndrome is a milder phenotype associated with ATP7A mutations; however the new drug is not indicated for its treatment.