Zydus Lifesciences Limited has achieved a major global healthcare milestone after its wholly owned US subsidiary Sentynl Therapeutics Inc. announced that the U.S. Food and Drug Administration has approved ZYCUBO® (copper histidinate) for the treatment of Menkes disease in pediatric patients. This approval marks a historic first, as ZYCUBO becomes the only FDA-approved therapy available for this rare and often fatal genetic disorder in the United States.
The approval represents a breakthrough moment for families affected by Menkes disease, a rare X-linked recessive condition caused by mutations in the ATP7A gene. Children born with this disorder are unable to absorb and transport copper properly, particularly across the blood-brain barrier, leading to severe neurological deterioration. Until now, there had been no approved treatment option available in the US, and most untreated patients did not survive beyond three years of age.
ZYCUBO is a subcutaneous injectable formulation of copper histidinate designed to restore copper homeostasis and maintain healthy copper levels in affected patients. By addressing the underlying copper deficiency at an early stage, the therapy offers a meaningful chance to alter the disease’s otherwise devastating course. Importantly, ZYCUBO is not indicated for the treatment of Occipital Horn Syndrome.
Commenting on the development, Dr. Sharvil P. Patel, Managing Director of Zydus Lifesciences, described the FDA approval as a transformative moment for the group and the rare disease community. He highlighted that, for the first time, patients and caregivers now have access to an approved therapy, bringing hope where no viable options previously existed and reinforcing Zydus’ commitment to advancing patient-centric innovation.
The FDA’s decision was supported by strong topline clinical efficacy data. Patients who received early treatment with ZYCUBO demonstrated a statistically significant improvement in overall survival compared with an untreated contemporaneous external control cohort. The results showed nearly an 80% reduction in the risk of death. Median overall survival for patients in the early-treatment group reached 177.1 months, compared with just 17.6 months in untreated patients, underscoring the therapy’s potential to dramatically change long-term outcomes.
Matt Heck, CEO of Sentynl Therapeutics, noted that Menkes disease poses immense challenges for patients and families due to the lack of a cure and historically poor survival rates. He stated that the FDA’s approval confirms that a safe and effective therapy is now available for children living with this devastating condition.
From a safety perspective, the most commonly reported adverse reactions, observed in at least 7% of patients, included pneumonia, viral and bacterial infections, respiratory failure, seizures, hemorrhage, hypotension, vomiting, tachycardia, fever, diarrhea, anemia, elevated transaminases, dyspnea, fractures, volume depletion, and local administration site reactions. These findings were consistent with expectations in a severely ill pediatric population.
ZYCUBO was acquired by Sentynl from Cyprium Therapeutics in 2023 and subsequently advanced through the final stages of regulatory development. The therapy received multiple FDA designations, including Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug status, reflecting its importance in addressing a critical unmet medical need. Copper histidinate has also been granted Orphan Drug Designation by the European Medicines Agency, opening the door for potential future approvals beyond the United States.