The U.S. Food and Drug Administration has issued a Complete Response Letter (CRL) for CUTX-101 (copper histidinate), a potential treatment for Menkes disease in pediatric patients, citing manufacturing deficiencies at the production facility. Fortress Biotech and its majority-owned subsidiary Cyprium Therapeutics announced the regulatory setback on October 1, 2025.
Manufacturing Issues Delay Approval
The CRL specifically noted current Good Manufacturing Practice (cGMP) deficiencies observed at the facility where CUTX-101 is manufactured. Importantly, the FDA did not cite any other approvability concerns and identified no deficiencies in CUTX-101's efficacy and safety data. The facility recently provided responses to the FDA's September 2025 re-inspection, and Sentynl Therapeutics expects to request a meeting with the FDA to discuss the CRL and resubmission strategy.
Sentynl Therapeutics, a U.S.-based biopharmaceutical company wholly-owned by Zydus Lifesciences, assumed full responsibility for CUTX-101's development and commercialization from Cyprium in December 2023. Cyprium expects its partner will work expeditiously to address the FDA's concerns and pursue resubmission promptly.
Clinical Evidence Supports Efficacy
The CUTX-101 New Drug Application was initially granted Priority Review by the FDA and is supported by positive topline clinical efficacy results demonstrating significant improvement in overall survival for Menkes disease subjects who received early treatment with CUTX-101. This clinical evidence underscores the therapeutic potential of the copper histidinate injection for addressing a critical unmet medical need.
Addressing a Rare Pediatric Disease
Menkes disease is a rare X-linked recessive pediatric disease caused by gene mutations of the copper transporter ATP7A. The minimum birth prevalence for Menkes disease is believed to be 1 in 34,810 live male births, and potentially as high as 1 in 8,664 live male births, based on recent genome-based ascertainment studies.
The condition is characterized by distinctive clinical features, including sparse and depigmented hair ("kinky hair"), connective tissue problems, and severe neurological symptoms such as seizures, hypotonia, failure to thrive, and neurodevelopmental delays. Mortality is high in untreated Menkes disease, with many patients dying between 2-3 years of age. Currently, there is no FDA-approved treatment for Menkes disease and its variants.
Financial Implications and Future Development
Under the transaction agreement with Sentynl, if CUTX-101 receives approval, Sentynl will transfer a Rare Pediatric Disease Priority Review Voucher to Cyprium. Additionally, Cyprium will be eligible to receive royalties on net sales of CUTX-101 and up to $129 million in aggregate development and sales milestones from Sentynl.
Cyprium and the National Institute of Child Health and Human Development also maintain an ongoing worldwide, exclusive license agreement to develop and commercialize adeno-associated virus (AAV)-based gene therapy, called AAV-ATP7A. This gene therapy is designed to deliver working copies of the copper transporter that is defective in patients with Menkes disease and is intended for use in combination with CUTX-101. AAV-ATP7A gene therapy is currently in pre-clinical development and has received FDA Orphan Drug Designation.
