Zydus-Owned Sentynl Gets USFDA Nod for First-Ever Menkes Disease Treatment ZYCUBO

This marks the first and only FDA-approved treatment for Menkes disease, a rare and often fatal genetic disorder, in the United States. ZYCUBO® is not indicated for the treatment of Occipital Horn Syndrome.

“Approval is a pivotal step towards achieving our goal of making a meaningful impact on patients, caregivers, and the rare disease community,” said Dr Sharvil P. Patel, Managing Director, Zydus Lifesciences Limited.

“This milestone marks a transformative moment for the Zydus Group and for families affected by Menkes disease. For the first time, patients have access to an approved therapy, offering hope where no options existed,” he added.

Menkes disease is a rare X-linked recessive pediatric disorder caused by mutations in the ATP7A gene, which encodes a copper transport protein. Affected patients are unable to properly absorb dietary copper, resulting in impaired copper transport across the blood-brain barrier. Until now, there had been no FDA-approved therapy available in the US.

ZYCUBO® is a subcutaneous injectable formulation of copper histidinate designed to restore copper homeostasis and maintain adequate copper levels in patients with Menkes disease.

“Menkes disease presents significant challenges for patients and their families. With no known cure, most untreated patients do not survive beyond three years of age,” said Matt Heck, CEO of Sentynl. “FDA approval affirms that a safe and effective therapy is now available for patients living with this devastating disease.”

The approval is supported by positive topline clinical efficacy data, which demonstrated a statistically significant improvement in overall survival among patients who received early treatment with ZYCUBO, compared to an untreated contemporaneous external control cohort. The data showed a nearly 80% reduction in the risk of death, with median overall survival of 177.1 months in the early-treatment cohort versus 17.6 months in untreated patients, according to US Prescribing Information.

The most commonly reported adverse reactions (≥7%) included pneumonia, viral infection, respiratory failure, seizures, bacterial infection, hemorrhage, hypotension, vomiting, tachycardia, pyrexia, volume depletion, fractures, dyspnea, elevated transaminases, diarrhea, fungal infection, anemia, and local administration reactions.

“This milestone represents the culmination of decades of research into understanding and treating Menkes disease,” said Dr Stephen Kaler, clinical genetics and genomics specialist at Columbia University Medical Center. “Early diagnosis and prompt initiation of copper histidinate therapy in affected neonates have been shown to reduce symptoms and prolong survival.”

Sentynl acquired ZYCUBO from Cyprium Therapeutics in 2023 and advanced the therapy through the final stages of regulatory review based on results from pivotal studies. The drug has received Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug Designations from the FDA. Copper histidinate has also been granted Orphan Designation by the European Medicines Agency.

Menkes disease is estimated to affect between 1 in 34,810 and 1 in 8,664 live male births, based on recent genome-based analyses. The disorder is characterized by distinctive features such as sparse, depigmented “kinky” hair, connective tissue abnormalities, and severe neurological symptoms including seizures, hypotonia, failure to thrive, and neurodevelopmental delays. Mortality remains high in untreated cases, with many patients dying between two and three years of age.

ZYCUBO® is the first FDA-approved bioavailable copper replacement therapy for Menkes disease and is administered daily via subcutaneous injection to deliver elemental copper.