The U.S. Food and Drug Administration (FDA) has accepted for priority review the New Drug Application (NDA) for CUTX-101 (copper histidinate), a product candidate developed by Sentynl Therapeutics for the treatment of Menkes disease. This rare, X-linked recessive pediatric condition, caused by mutations in the ATP7A gene, affects copper transport and leads to severe neurological symptoms and early mortality. The FDA's decision, announced January 6, 2025, marks a significant step toward potentially providing the first FDA-approved treatment for this devastating condition.
Clinical Efficacy and Priority Review
The NDA submission for CUTX-101 is supported by compelling clinical efficacy results. Data from clinical trials demonstrated a statistically significant improvement in overall survival for Menkes disease patients who received early treatment with CUTX-101. Specifically, early treatment was associated with a nearly 80% reduction in the risk of death compared to an untreated historical control cohort. The median overall survival was 177.1 months for the CUTX-101 early treatment group, compared to only 16.1 months for the untreated control group.
The FDA's priority review designation accelerates the review process, setting a PDUFA (Prescription Drug User Fee Act) target action date of June 30, 2025. This expedited review is reserved for therapies that, if approved, would represent a significant improvement in safety or effectiveness in the treatment of a serious condition.
Unmet Need in Menkes Disease
Menkes disease affects an estimated 1 in 34,810 to 1 in 8,664 live male births. The ATP7A gene mutations disrupt copper transport, leading to a range of debilitating symptoms, including sparse and depigmented hair, connective tissue problems, seizures, hypotonia, and neurodevelopmental delays. Without treatment, mortality is high, with most patients dying between 2 and 3 years of age. Currently, there are no FDA-approved therapies specifically for Menkes disease, underscoring the urgent need for effective treatments.
Matt Heck, President & Chief Executive Officer of Sentynl, emphasized the critical need for new therapies, stating, “Menkes disease presents a difficult journey for patients and their caregivers... With no known cure or current FDA-approved treatments, death typically occurs between 2 to 3 years of age. We are eager for the FDA to review our application for CUTX-101, which has the potential to be the first FDA-approved therapy for this devastating condition.”
CUTX-101: Development and Regulatory Designations
CUTX-101 is a subcutaneous injectable formulation of copper histidinate, designed to improve tolerability due to its physiological pH. It has been granted several key designations by the FDA, including Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug Designations. The European Medicines Agency (EMA) has also granted Orphan Drug Designation for CUTX-101.
In December 2023, Sentynl Therapeutics assumed full responsibility for the development and commercialization of CUTX-101 from Cyprium Therapeutics, a subsidiary of Fortress Biotech. Cyprium is eligible to receive royalties and up to $129 million in aggregate development and sales milestones from Sentynl. Cyprium also retains ownership of any Priority Review Voucher (PRV) that may be issued upon NDA approval, which can be redeemed for a subsequent marketing application or sold to a third party.
Lindsay A. Rosenwald, M.D., Chairman, President and Chief Executive Officer of Fortress and Chairman of Cyprium, commented, “We congratulate Sentynl on the NDA acceptance for filing and review of CUTX-101, a program that Cyprium advanced and proudly supports... The drug has a demonstrated safety and efficacy profile for the treatment of Menkes disease and, if approved, CUTX-101 will fill a significant unmet need for children suffering from this rare, fatal pediatric disease.”
With the FDA's priority review underway, the potential approval of CUTX-101 offers a beacon of hope for patients and families affected by Menkes disease, potentially transforming the treatment landscape for this devastating condition.
