FDA Rejects Fortress and Sentynl's Treatment for Rare Pediatric Disease

The U.S. Food and Drug Administration (FDA) has issued a complete response letter rejecting the investigational treatment CUTX-101 for Menkes disease, a rare genetic disorder, developed by Fortress Biotech and Sentynl Therapeutics. The decision, announced on Wednesday, cited manufacturing facility issues as the primary reason for the rejection.

Manufacturing Concerns Halt Progress

The FDA's complete response letter highlighted problems at the manufacturing facility where CUTX-101 is produced. Fortress Biotech stated that the plant in question has already responded to these observations. Notably, the regulator did not identify any deficiencies with the drug's efficacy or safety data, nor were there any other issues with the application itself.

This rejection follows a trend of manufacturing-related setbacks in the pharmaceutical industry. Recent FDA decisions for Biogen's high-dose formulation of Spinraza and Scholar Rock's apitegromab were similarly based on manufacturing site issues rather than concerns about the therapies themselves.

CUTX-101: A Promising Treatment for Menkes Disease

Menkes disease, affecting approximately 1 in 100,000 infants, is characterized by sparse and depigmented hair, seizures, intellectual disability, and developmental delays. The genetic disorder is caused by mutations in the ATP7A gene, which disrupts normal copper distribution in the body.

CUTX-101, a subcutaneous formulation of copper histidinate, showed promising results in clinical trials. A midstage trial reported in October 2021 demonstrated that the treatment reduced the risk of death by 80% compared to untreated historical controls. Early intervention with CUTX-101 resulted in a median overall survival of 177.1 months, significantly higher than the 16.1 months observed in controls.

Financial Implications and Future Steps

Sentynl Therapeutics acquired CUTX-101 in February 2021 for $20 million. If approved, Fortress Biotech stands to receive up to $129 million in aggregate development and sales milestones, plus royalties on net sales. The FDA granted CUTX-101 a rare pediatric disease designation in January 2020, potentially qualifying it for a priority review voucher upon approval.

Fortress Biotech and Sentynl Therapeutics plan to seek a meeting with the FDA to discuss resubmission of their application. The companies remain optimistic about the potential of CUTX-101, given the absence of safety or efficacy concerns in the FDA's response.