FDA Approves ZYCUBO as First Treatment for Rare Menkes Disease

Fortress Biotech, Inc. and its majority-owned subsidiary Cyprium Therapeutics have received a major regulatory milestone with the U.S. Food and Drug Administration’s approval of ZYCUBO® (copper histidinate) for the treatment of pediatric patients with Menkes disease. The approval marks the first FDA-authorized therapy for this rare and often fatal genetic disorder, providing a long-awaited treatment option for affected children and their families.

ZYCUBO, previously known as CUTX-101, is a subcutaneous injectable formulation of copper histidinate designed to restore and maintain copper homeostasis in patients with Menkes disease. The condition is a rare X-linked recessive disorder caused by mutations in the ATP7A gene, which impair the body’s ability to absorb and transport dietary copper, particularly to the brain. Without treatment, patients experience severe neurodegeneration and early mortality, and until now, no approved therapy had been available in the United States.

As part of the FDA approval, a Rare Pediatric Disease Priority Review Voucher (PRV) was issued. Under a previously announced agreement, Sentynl Therapeutics— a U.S.-based biopharmaceutical company wholly owned by Zydus Lifesciences Limited—assumed full responsibility for the development and commercialization of ZYCUBO in December 2023. The PRV will be transferred to Cyprium pursuant to the transaction terms. In addition, Cyprium is eligible to receive tiered royalties on net sales of ZYCUBO, along with up to $129 million in potential development and sales milestone payments from Sentynl.

Clinical data supporting the approval demonstrated a significant survival benefit in patients treated early with ZYCUBO. In a comparative analysis, early-treated patients showed a nearly 80% reduction in the risk of death compared with an untreated external control cohort. Median overall survival reached 177.1 months in the ZYCUBO-treated group, versus 17.6 months in untreated patients, underscoring the therapy’s potential to dramatically alter the disease course.

Company leadership described the approval as a transformative moment. Fortress Chairman, President and CEO Dr. Lindsay A. Rosenwald highlighted that ZYCUBO represents the company’s third FDA approval in the past 15 months, reflecting continued execution across its diversified portfolio. Cyprium President and CEO Dr. Lung S. Yam emphasized the decades-long effort behind the program and expressed gratitude to patients and families who participated in clinical studies.

ZYCUBO has received multiple FDA designations, including Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug status, while copper histidinate has also been granted Orphan Designation by the European Medicines Agency, reinforcing its importance in addressing a significant unmet medical need.