The U.S. Food and Drug Administration has approved Zycubo, a drug developed by Fortress Biotech and Zydus Lifesciences, for the treatment of pediatric patients with Menkes disease, a rare inherited disorder that affects copper absorption. Fortress Biotech announced the approval on Tuesday, stating that it represents the first drug authorized to treat the disease in the United States.
Following the announcement, shares of Fortress Biotech rose more than 13% in premarket trading. Zycubo, also known chemically as CUTX-101, is a subcutaneous injectable formulation of copper histidinate. The drug delivers copper directly into the body to avoid absorption through the gastrointestinal tract and is intended to increase copper levels in the blood to improve body and brain function.
Menkes disease is caused by mutations in the ATP7A gene, which is responsible for copper transport throughout the body. Patients are born unable to absorb dietary copper and subsequently experience impaired copper transport across the blood-brain barrier. The disease is X-linked recessive and primarily affects male infants. According to the companies, recent estimates suggest a prevalence ranging from 1 in 34,810 to as high as 1 in 8,664 live male births.
Symptoms of Menkes disease include sparse and depigmented hair, seizures, and developmental delays. If untreated, many patients die between the ages of two and three. Until this approval, there had been no FDA-approved treatment available in the United States. Current treatments include daily copper injections.
The FDA approval was supported by clinical data showing improved survival outcomes among patients who received early treatment with Zycubo. According to the results, patients treated early experienced a nearly 80% reduction in the risk of death compared with untreated individuals. Median overall survival was reported at 177.1 months for the early-treatment cohort, compared with 17.6 months for an untreated contemporaneous external control cohort.
Fortress Biotech and its majority-owned subsidiary, Cyprium Therapeutics, are eligible to receive tiered royalties on net sales of Zycubo and up to $129 million in aggregate development and sales milestone payments from Sentynl Therapeutics. In December 2023, Sentynl, a U.S.-based biopharmaceutical company wholly owned by Zydus Lifesciences, assumed full responsibility for the development and commercialization of CUTX-101 from Cyprium.
Lindsay A. Rosenwald, M.D., chairman, president, and chief executive officer of Fortress Biotech and chairman of Cyprium, said, “The approval of ZYCUBO is a pivotal milestone for our company and patients suffering from Menkes Disease, as it is the first and only FDA-approved treatment for this rare, often fatal, pediatric disease.”
The most common adverse reactions reported, with an incidence of at least 7%, included pneumonia, viral infection, respiratory failure, seizures, bacterial infection, hemorrhage, hypotension, vomiting, tachycardia, fever, volume depletion, fractures, dyspnea, elevated transaminases, diarrhea, fungal infection, anemia, and local administration reactions.
Zycubo has received Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations from the FDA. Copper histidinate has also been granted Orphan Drug designation by the European Medicines Agency.
Clinical Evidence Supporting Zycubo
The FDA based its approval of Zycubo on data from two open-label clinical trials involving pediatric patients treated for up to three years. The results were striking:
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Infants who began Zycubo treatment within the first four weeks of life showed a 78% reduction in the risk of death compared to untreated patients.
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Nearly half of these early-treated children survived beyond age six, and some well past age twelve—a substantial improvement over historical outcomes.
These results demonstrate that Zycubo can significantly extend survival and improve long-term outcomes when therapy is initiated early.
Zycubo’s approval represents a major advancement for the rare disease community. For families coping with Menkes disease, this therapy provides:
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The only FDA-approved treatment option in the United States.
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A scientifically validated approach to restoring essential copper levels.
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Increased hope for meaningful improvements in survival and quality of life for affected children.
