FDA Grants Priority Review to CUTX-101 NDA for Menkes Disease

On January 6, 2025, Fortress Biotech, Inc. and its subsidiary Cyprium Therapeutics announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for CUTX-101, aimed at treating Menkes disease. This rare pediatric disorder is caused by mutations in the ATP7A gene, which affect copper transport within the body. The FDA has given CUTX-101 Priority Review status, setting a target action date of June 30, 2025.

In a strategic shift made in December 2023, Sentynl Therapeutics, a biopharmaceutical firm under the Zydus Group, took over full responsibility for developing and commercializing CUTX-101 from Cyprium. Sentynl completed the NDA submission and will manage its commercialization upon approval. Under the terms of their agreement, Cyprium stands to earn royalties and maintains ownership of any Priority Review Voucher issued upon NDA approval.

The NDA for CUTX-101 is backed by promising clinical trial results demonstrating significant efficacy. Early recipients of CUTX-101 showed a nearly 80% reduction in mortality risk compared to historical controls. In numerical terms, patients receiving early treatment had a median survival rate of 177.1 months, versus just 16.1 months for those untreated. The FDA had previously granted CUTX-101 several designations, including Breakthrough Therapy and Orphan Drug, while the European Medicines Agency has also recognized it with Orphan Drug Designation.

"This NDA submission marks a crucial moment for both our company and the affected families," stated Lindsay A. Rosenwald, Chairman and CEO of Fortress and Cyprium. "We are hopeful that CUTX-101 could become the first FDA-approved treatment for Menkes disease, providing a new ray of hope for this severe condition."

Menkes disease is a debilitating disorder due to ATP7A mutations, impairing copper transport to essential organs like the brain and heart. Left untreated, the disease often leads to death by the age of three. "Given the severe impact of Menkes disease, we're eager for the FDA's review of our application for CUTX-101, as it could be the first approved treatment for this challenging condition," said Matt Heck, President & CEO of Sentynl.

If approved, CUTX-101 may qualify for a Rare Pediatric Disease Priority Review Voucher, which Cyprium retains the right to either use or sell. The company could also receive up to $129 million in development and sales milestones.

CUTX-101 is a subcutaneous injectable formulation of copper histidinate, designed to enhance tolerability through its physiological pH. Early trials, led by Stephen G. Kaler at the NIH, showed improvements in neurodevelopmental outcomes and survival for Menkes patients. Cyprium continues collaborative efforts with the NIH to advance CUTX-101 and related gene therapies. Additionally, an expanded access protocol is ongoing in the U.S., allowing broader patient participation.

While Menkes disease has a variable birth prevalence, it is a serious condition marked by neurological impairments and high mortality. Despite minimal options, Cyprium remains committed to exploring therapies that address copper metabolism disorders. Their collaborative work with the NIH includes developing a gene therapy, AAV-ATP7A, to correct the underlying genetic defect in Menkes disease.

Sentynl Therapeutics, committed to rare disease treatments, was acquired by the Zydus Group in 2017. The company aims to commercialize promising therapies like CUTX-101, focusing on innovative, patient-centric solutions in challenging medical fields.