Fortress Biotech, Inc., an innovative revenue-generating company focused on acquiring, developing and commercializing or monetizing promising biopharmaceutical products and product candidates cost-effectively, announced that the U.S. Food and Drug Administration (“FDA”) has granted Breakthrough Therapy Designation to Cyprium Therapeutics for CUTX-101, a potential treatment for Menkes disease. Often lethal if untreated, Menkes disease is an X-linked recessive disorder of copper metabolism caused by mutations in ATP7A, an evolutionarily conserved copper-transporting ATPase. The FDA previously granted Orphan Drug, Fast Track, and Rare Pediatric Disease Designations to CUTX-101 for the treatment of Menkes disease. Additionally, the European Medicines Agency previously granted Orphan Drug Designation to CUTX-101.

“We are very pleased that the FDA has granted Breakthrough Therapy Designation to CUTX-101, a devastating pediatric disease with no FDA-approved treatment options currently available. The positive topline clinical efficacy data reported earlier this year highlight the potential of CUTX-101 to be a safe and effective therapy and fulfill a significant unmet medical need for patients with Menkes disease. We look forward to beginning our rolling submission of a New Drug Application (“NDA”) to the FDA for CUTX-101 in the first quarter of next year. Our goal is to bring this treatment to patients as soon as possible,” said Lung S. Yam, M.D., Ph.D., President and Chief Executive Officer of Cyprium.

Breakthrough Therapy Designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for Breakthrough Therapy Designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. A Breakthrough Therapy Designation conveys all of the fast-track program features, more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior managers and eligibility for rolling review and priority review.

Menkes disease is a rare X-linked recessive pediatric disease caused by gene mutations of copper transporter ATP7A. The minimum birth prevalence for Menkes disease is believed to be 1 in 34,810 males, and potentially as high as 1 in 8,664 live male births, based on recent genome-based ascertainment (Kaler SG, Ferreira CR, Yam LS. Estimated birth prevalence of Menkes disease and ATP7A-related disorders based on the Genome Aggregation Database (gnomAD). Mol Genet Metab Rep. 2020 Jun 5;24:100602). Biochemically, patients with Menkes disease have low levels of copper in their blood and brain, as well as abnormal levels of certain neurochemicals. Definitive diagnosis is made by sequencing the ATP7A gene. The condition is characterized by distinctive clinical features, including sparse and depigmented hair (“kinky hair”), connective tissue problems, and severe neurological symptoms such as seizures, hypotonia, failure to thrive, and neurodevelopmental delays. Mortality is high in untreated Menkes disease, with many patients dying before the age of three years. Milder versions of ATP7A mutations are associated with other conditions, including Occipital Horn Syndrome and ATP7A-related Distal Motor Neuropathy. Currently, there is no FDA-approved treatment for Menkes disease and its variants.

CUTX-101 is in clinical development to treat patients with Menkes disease by replenishing Copper Histidinate, restoring copper homeostasis and maintaining serum copper levels in the normal age appropriate range. CUTX-101 is a subcutaneous injectable formulation of Copper Histidinate manufactured under current good manufacturing practice (“cGMP”) and physiological pH that bypasses the defect in absorption of orally administered copper in patients with Menkes disease. In a Phase 1/2 clinical trial conducted by Stephen G. Kaler, M.D., M.P.H., at the National Institutes of Health (“NIH”), early treatment of patients with Menkes disease with CUTX-101 led to an improvement in neurodevelopmental outcomes and survival. A Phase 3 trial of CUTX-101 in patients with Menkes disease also led by Dr Kaler has completed enrollment. In August 2020, Cyprium reported positive topline clinical efficacy results for CUTX-101, demonstrating statistically significant improvement in overall survival for Menkes disease subjects who received early treatment (ET) with CUTX-101, compared to an untreated historical control (HC) cohort, with a nearly 80% reduction in the risk of death.