FDA Announces Priority Review for CUTX-101 to Treat Menkes Disease

According to a news release from Fortress Biotech and Cyprium Therapeutics, the FDA has accepted the review of the new drug application (NDA) for CUTX-101, a subcutaneous injectable formulation of copper histidinate, for the treatment of patients with Menkes disease. Additionally, the FDA has granted the NDA priority review, assigning CUTX-101 a Prescription Drug User Fee Act (PDFUA) target action date of June 30, 2025.¹

Menkes disease is a rare but potentially debilitating pediatric condition. | Image Credit: © Magnimage | stock.adobe.com

Previously, the FDA granted breakthrough therapy, fast track, rare pediatric disease, and orphan drug designations to CUTX-101. A positive efficacy and safety analysis of 2 completed pivotal studies in patients with Menkes disease treated with CUTX-101 provide the backing for the NDA’s acceptance and was released in October 2021 as a virtual poster at the 2021 American Academy of Pediatrics National Conference and Exhibition.²

The analysis, led by Stephen G. Kaler, MD, MPH, met the primary efficacy end point of overall survival (OS). Patients with Menkes disease treated early with CUTX-101 had an almost 80% reduction in the risk of death, compared with an untreated historical control cohort. Further, a secondary OS end point was met as patients treated with CUTX-101 had a median OS of 177.1, compared with 16.1 months for untreated patients. Importantly, a sensitivity analysis revealed that CUTX-101 was effective at increasing OS regardless of severe ATP7A mutation time or prematurity.³

“Menkes disease presents a difficult journey for patients and their caregivers, as ATP7A mutations impact the transport of copper to a range of organs and systems, such as the lungs, brain and heart,” Matt Heck, president and chief executive officer (CEO) of Sentynl, explained in the news release. “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.”¹

Menkes disease, a rare, X-linked recessive pediatric disease, is caused by mutations of the copper transporter ATP7A. It is characterized by a distinctive clinical appearance, featuring sparse and depigmented hair, connective tissue difficulties, and serious neurological complications including seizures, hypotonia, and neurodevelopmental delays. It is believed that the minimum birth prevalence for Menkes disease is 1 in 34,810 live male births, and potentially as high as 1 in 8664 live male births based on recent genome-based ascertainment analysis. Unfortunately, mortality is high in patients who go untreated, with many dying between 2 to 3 years of age.¹

In the landmark analysis, investigators found that treatment emergent adverse events (TEAEs) were reported in 61 subjects (92.4%), though none were considered related to treatment with CUTX-101. Furthermore, serious TEAEs were reported in 50 subjects (75.8%), with TEAEs that led to death and discontinuation of the study treatment being reported in 19 subjects (28.8%). Still, none of these serious complications were considered associated with CUTX-101 treatment.³

“We are thrilled that the NDA for CUTX-101 for the treatment of Menkes disease was accepted for review by the FDA and look forward to working with…the FDA during its review period,” Lindsay A Rosenwald, MD, chairman, president, and CEO of Fortress and chairman of Cyprium, said in the news release. “CUTX-101 could be the first FDA-approved treatment for Menkes disease, making this submission an important milestone…for the patients suffering from this rare, often fatal, pediatric disease.”¹

Pharmacists should stay aware of developments surrounding CUTX-101 throughout its approval process.

REFERENCES

1. Fortress Biotech. Fortress Biotech and Cyprium Therapeutics announce U.S. FDA acceptance and priority review of NDA for CUTX-101 for treatment of Menkes disease. News Release. Released January 6, 2025. Accessed January 7, 2025. https://finance.yahoo.com/news/fortress-biotech-cyprium-therapeutics-announce-130000782.html?guccounter=1&guce_referrer=aHR0cHM6Ly9zdGF0aWNzLnRlYW1zLmNkbi5vZmZpY2UubmV0Lw&guce_referrer_sig=AQAAAA0VYf4HDzKRybAEfunSJnhfn8pW-ONXCI2n9C_2pqJTMFFNd-LdsstIbz8KtX-zD_vLWrB_iGdXvlVcETFHtwssNM01UGjfzTs48z0OfpcViU8nTZSA4cl8c5-mv7n6lid2elc6jdK23SOa-DzxZf0OilBPZnBjexReh9GHDz0w

2. Cyprium Therapeutics. Fortress Biotech and Cyprium Therapeutics announce positive clinical data for CUTX-101, copper histidinate, presented at 2021 American Academy of Pediatrics National Conference & Exhibition. News Release. Released October 8, 2021. Accessed January 7, 2025. https://www.biospace.com/fortress-biotech-and-cyprium-therapeutics-announce-positive-clinical-data-for-cutx-101-copper-histidinate-presented-at-2021-american-academy-of-pediatrics-national-conference-and-exhibition

3. Kaler SG, Munim S, Chen M, et al. Copper histidinate treatment for Menkes disease (kinky hair syndrome). Presented at the American Academy of Pediatrics National Conference & Exhibition, October 8-12, 2021. Accessed online January 7, 2025. https://www.cypriumtx.com/wp-content/uploads/2021/10/Kaler-et-al-AAP-Poster_final-draft_24SEP2021.pdf