FDA Rejects Cyprium-Sentynl's Menkes Disease Treatment Due to Manufacturing Issues

The U.S. Food and Drug Administration (FDA) has issued a complete response letter for CUTX-101, a copper histidinate drug candidate developed by Cyprium Therapeutics and Sentynl Therapeutics for the treatment of Menkes disease. The decision, centered on manufacturing deficiencies, halts progress towards what could have been the first approved treatment for this rare and often fatal pediatric condition.

Manufacturing Concerns Prompt FDA Action

According to a press release from October 1, 2025, the FDA's concerns stem from deficiencies noted during an inspection of the manufacturing facility for CUTX-101. The regulatory body had conducted a reinspection of the plant in September, with Sentynl Therapeutics now awaiting the official inspection report.

Matt Heck, CEO of Sentynl Therapeutics, expressed the company's commitment to addressing the FDA's feedback, stating, "We believe in the promise of our therapy and are prepared to address the feedback and pursue resubmission promptly." Importantly, the complete response letter did not raise issues regarding the drug's safety or efficacy data.

CUTX-101: A Potential Breakthrough for Menkes Disease

CUTX-101 is a subcutaneous injectable formulation of copper histidine designed to restore copper homeostasis in patients with Menkes disease. This rare genetic disorder, caused by mutations in the ATP7A gene, affects copper metabolism and transport across the blood-brain barrier. The condition is extremely rare, with an estimated prevalence between 1 in 34,810 and 1 in 8,664 live male births.

Clinical trial results for CUTX-101 have been promising. The drug demonstrated a nearly 80% reduction in the risk of death for patients who received early treatment compared to an untreated historical control cohort. Treated patients lived a median of 177.1 months (14.76 years), significantly longer than the 16.1 months recorded in the historical control group.

Collaborative Efforts and Future Prospects

The development of CUTX-101 has been a collaborative effort between Cyprium Therapeutics, a subsidiary of Fortress Biotech focused on copper metabolic diseases, and Sentynl Therapeutics, a subsidiary of Zydus Lifesciences. Their partnership began with a $20 million asset purchase agreement in 2021, which was expanded in 2023 to give Sentynl full responsibility for the drug's development and commercialization.

If CUTX-101 ultimately gains approval, Cyprium stands to receive royalties on net sales and up to $129 million in milestone payments. Additionally, Sentynl would transfer a rare pediatric disease priority review voucher to Cyprium if granted by the FDA.

As Sentynl prepares to request a meeting with the FDA to discuss resubmission, the future of this potentially life-saving treatment for children with Menkes disease hangs in the balance, dependent on resolving the manufacturing issues identified by the regulatory agency.