Breakthrough: FDA Approves Zycubo for Pediatric Menkes Disease

The U.S. Food and Drug Administration has approved Zycubo (copper histidinate) from Sentynl Therapeutics for pediatric patients with Menkes disease — the first authorized therapy for this genetic copper‑transport disorder, filling a long‑standing therapeutic gap.

Until now, management relied largely on supportive care and experimental or off‑label copper replacement with variable formulations and access. An approved, standardized copper histidinate product establishes a labeled treatment pathway with more consistent dosing and supply expectations, while not guaranteeing immediate availability in all settings. Copper histidinate supplies bioavailable copper for systemic redistribution and helps restore activity of copper‑dependent enzymes that are impaired in Menkes disease.

Across two open‑label, single‑arm studies in neonates and infants where survival was the primary endpoint, the clinical trial data demonstrated a 78% relative reduction in the risk of death for patients who began therapy within four weeks of birth versus untreated comparators. The survival benefit was greatest when treatment started in the first month of life and was smaller or less certain for later starts in infancy. These outcomes emphasize the importance of early identification and rapid treatment initiation and support expedited diagnostic pathways for newborns at risk of Menkes disease.

The principal safety concern is potential copper accumulation with repeated dosing. Recommended monitoring includes baseline and periodic serum copper and ceruloplasmin, liver function tests, focused neurologic assessment, and vigilance for signs of copper toxicity such as unexplained gastrointestinal symptoms or worsening neurologic status. Zycubo is administered by subcutaneous injection; administration logistics and pediatric dosing protocols will determine whether initiation and early doses occur in outpatient clinics, specialized centers, or hospital settings. Routine laboratory and clinical monitoring can mitigate accumulation risk and permit safe outpatient management once patients are stabilized.