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The FDA opened 2026 with a rare-disease approval anchored in metabolic correction. On January 12, the agency approved Zycubo (copper histidinate) from Sentynl Therapeutics for the treatment of Menkes disease, a lethal X-linked disorder of copper transport that presents in infancy and rapidly progresses without intervention.
Zycubo
Zycubo is a parenteral copper replacement therapy designed to bypass defective intestinal absorption caused by pathogenic variants in ATP7A.
By delivering bioavailable copper histidinate via subcutaneous injection, the drug restores copper homeostasis and supports copper-dependent enzymatic activity critical to neurologic development, connective tissue integrity, and vascular function. The mechanism is straightforward, but the clinical stakes are high: untreated Menkes disease is typically fatal, with many patients not surviving past three years of age.
Approval was supported by two open-label, single-arm clinical studies with external contemporaneous controls. In infants treated within four weeks of birth, Zycubo demonstrated a 78% reduction in the risk of death compared to untreated patients.
Nearly half of these early-treated patients were alive at a six-year follow-up, with some surviving more than 12 years, whereas no patients in the untreated control group survived beyond six years. Later initiation also provided a substantial survival benefit, though outcomes were less pronounced, reinforcing the importance of early diagnosis.
Safety labeling emphasizes monitoring for copper accumulation and potential organ toxicity, specifically drug-induced kidney injury and liver dysfunction, alongside risks common to a medically fragile population such as seizures and infections.
The Strategic Brief
Zycubo is a structurally important approval, formalizing copper replacement in Menkes disease and replacing off-label, compounded care with the first and only FDA-approved, standardized therapy for the condition. While population-limited, the decision reinforces FDA openness to well-characterized metabolic replacement strategies in ultra-rare pediatric disorders where randomized trials are not feasible.
Sources
U.S. FDA press announcement – Zycubo (copper histidinate) approval – 01/12/2026
FDA prescribing information – Zycubo
Sentynl Therapeutics press release – Zycubo - 01/13/2026
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