The FDA has issued a manufacturing-related complete response letter for Cyprium Therapeutics’ copper histidinate drug candidate CUTX-101, raising a roadblock on the path to commercializing the first treatment for children with rare and often fatal Menkes disease.
Zydus Lifesciences' subsidiary, Sentynl Therapeutics—which has full development and commercialization responsibilities for the drug—will request a meeting with the FDA to discuss a resubmission, according to an Oct.1 press release.
According to the companies, the agency’s concerns center on deficiencies noted at an inspection of the plant that makes CUTX-101. The FDA reinspected the facility in September, and Sentynl is waiting for the agency’s official inspection report.
Sentynl remains “dedicated to working with the agency to clarify next steps,” CEO Matt Heck said.
“We believe in the promise of our therapy and are prepared to address the feedback and pursue resubmission promptly,” the Sentynl leader CEO added. The complete response letter did not cite other approvability concerns or issues with the drug’s safety and efficacy data.
CUTX-101 is a subcutaneous injectable formulation of copper histidine designed to restore copper homeostasis and maintain copper levels in patients with Menkes disease.
Children born with Menkes suffer from severe neurological symptoms and typically pass away between the ages of 2 and 3 years old. The disease is a rare pediatric disease hallmarked by genetic mutations in the ATP7A gene, a copper transporter that impacts the body’s copper cells.
ATP7A mutations can prevent dietary copper from properly metabolizing and transporting across the blood-brain barrier. Menkes disease is extremely rare, with a prevalence ranging between 1 in every 34,810 live male births to 1 in 8,664 live male births, according to Fortress Biotech's subsidiary Cyprium.
In a clinical trial, CUTX-101 achieved a nearly 80% reduction in the risk of death for Menkes disease patients who received early treatment, compared with an untreated historical control cohort, according to Cyprium. The drug helped patients live a median of 177.1 months (14.76 years) over the 16.1 months recorded in the historical control group.
Sentynl and Cyrium, a copper metabolic disease-focused company within Fortress, have been working together on the drug since a $20 million asset purchase agreement in 2021. At the time, Cyprium hoped that the deal would “potentially expedite” its development and commercialization. The agreement was expanded in 2023 to give Sentynl full responsibility for the development and commercialization of its products.
If approved, Cyprium will receive royalties on the drug’s net sales and up to $129 million in milestone payments. Sentynl will also transfer over a rare disease pediatric disease priority review voucher if granted by the FDA.