FDA Rejects Fortress and Sentynl's Treatment for Rare Pediatric Disease, Citing Manufacturing Issues

The U.S. Food and Drug Administration (FDA) has rejected the investigational treatment for Menkes disease developed by Fortress Biotech and Sentynl Therapeutics. The decision, announced on Wednesday, marks another setback in the rare disease space, where manufacturing issues continue to challenge drug approvals.

Manufacturing Concerns Stall Approval

In its complete response letter, the FDA cited issues at the manufacturing facility where the drug, CUTX-101, is produced. Fortress Biotech stated that the plant in question has already responded to these observations. Notably, the FDA did not identify any deficiencies with the drug's efficacy or safety data, focusing solely on manufacturing concerns.

This rejection follows a pattern of recent FDA decisions where manufacturing issues have impeded regulatory bids. Similar challenges recently affected Biogen's high-dose formulation of Spinraza and Scholar Rock's apitegromab, both of which were rejected due to manufacturing site issues rather than concerns about the therapies themselves.

CUTX-101: A Potential Breakthrough for Menkes Disease

CUTX-101, a subcutaneous formulation of copper histidinate, showed promising results in clinical trials for the treatment of Menkes disease. This rare genetic disorder, affecting approximately 1 in 100,000 infants, is characterized by sparse and depigmented hair, seizures, intellectual disability, and developmental delays. It typically leads to death by three years of age.

In a midstage trial, CUTX-101 demonstrated significant efficacy, reducing the risk of death by 80% in treated patients compared to untreated historical controls. Early intervention with the drug resulted in a median overall survival of 177.1 months, versus 16.1 months in controls.

Next Steps and Industry Implications

Sentynl Therapeutics, which acquired CUTX-101 from Fortress Biotech in February 2021 for $20 million, plans to seek a meeting with the FDA to discuss resubmission. If approved, Fortress stands to receive up to $129 million in aggregate development and sales milestones, plus royalties on net sales.

The rejection of CUTX-101 highlights the ongoing challenges in the rare disease drug development landscape. While FDA Commissioner Marty Makary has publicly expressed openness to expedited approvals for rare disease treatments, recent months have seen a mix of rejections and approvals in this space.

Despite this setback, the rare disease sector has seen notable successes, including recent FDA approvals for four industry firsts: Jazz Pharmaceuticals' Modeyso for Glioma, Insmed's Brinsupri for non-cystic fibrosis bronchiectasis, Precigen's Papzimeos for recurrent respiratory papillomatosis, and Ionis' Dawnzera for hereditary angioedema.

As the pharmaceutical industry continues to navigate the complex regulatory landscape for rare disease treatments, manufacturing capabilities remain a critical factor in securing FDA approvals.