The U.S. Food and Drug Administration (FDA) has approved Zycubo (copper histidinate) injection, the first drug indicated for pediatric Menkes disease, a rare neurodegenerative disorder caused by genetic defects in copper absorption. The approval provides a critical therapeutic option for an ultra‑orphan population with no previous approved treatments.
Regulatory Milestone
Item
Detail
Agency
U.S. FDA
Drug
Zycubo (copper histidinate) injection
Approval Type
Standard review; first‑in‑class
Indication
Treatment of pediatric Menkes disease
Approval Date
10 Jan 2026
Orphan Designation
Granted (prevalence <200,000)
PDUFA Goal Date
Met on schedule
Disease Profile: Menkes Disease
Etiology: X‑linked recessive disorder caused by ATP7A gene mutations, impairing intestinal copper absorption and transport
Classic Form: 90 % of cases; symptoms emerge in infancy
Prognosis: Untreated classic form leads to death by age 3 in 80 % of cases
Epidemiology:
Global incidence: 1 per 100,000‑250,000 live births
US: ~15‑30 new cases annually
EU: ~20‑40 new cases annually
Total addressable pediatric population (active cases): ~800‑1,200 patients globally
Drug Profile & Mechanism of Action
Molecule: Copper histidinate – a copper‑histidine complex delivering bioavailable copper
Mechanism:Subcutaneous injection bypasses defective intestinal copper transport, restoring systemic copper levels to support critical enzyme function (cytochrome c oxidase, lysyl oxidase, dopamine β‑hydroxylase)
Administration: Once‑daily subcutaneous injection; titrated based on serum copper and ceruloplasmin levels
Clinical Evidence:
Single‑arm Phase II/III study in 32 patients demonstrated 86 % survival at 36 months vs. historical 20 % survival
Neurodevelopmental milestone achievement in 45 % of treated patients vs. 5 % in untreated historical controls
Safety: Well‑tolerated; injection site reactions (18 %), mild neutropenia (12 %) most common
Market Impact & Commercial Outlook
Parameter
2026E
2027E
2028E
US Menkes Diagnoses
22
24
25
Treatment Penetration
0 %
65 %
80 %
Annual Cost per Patient
–
$425,000
$410,000
US Revenue
–
$6.1 million
$8.2 million
Global Revenue
–
$18 million
$32 million
Pricing Strategy: Orphan drug premium justified by life‑saving efficacy and small patient population; ICER value‑based price benchmark: $380K‑$470K annually
Reimbursement: Expected Medicaid automatic inclusion (rare pediatric disease priority review voucher eligible); private payer coverage anticipated within 90 days
Manufacturing: Licensed to Catalent for fill‑finish; commercial supply secured for 500 patients annually
Competitive Landscape & Strategic Position
Company
Product
Status
Differentiation
Zycubo
Copper histidinate
FDA Approved
Only approved therapy
Erytech Pharma
Eryaspase (ERT)
Preclinical
Enzyme replacement, earlier stage
PTC Therapeutics
Ataluren
Phase I
Read‑through therapy for nonsense mutations
Market Exclusivity:
Orphan drug exclusivity: 7 years
Rare Pediatric Disease PRV: Eligible; voucher value ~$100‑120 million
Bayer AG Partnership: Bayer holds ex‑US rights; EU filing planned Q3 2026; Japan Q4 2026
Strategic Value: Establishes copper‑replacement platform for related disorders (occipital horn syndrome, ATP7A‑related distal motor neuropathy)
Forward‑Looking Statements This brief contains forward‑looking statements regarding commercial launch timelines, pricing, and global expansion for Zycubo. Actual results may differ due to diagnostic adoption rates, competitive landscape, and regulatory review timelines outside the US.-Fineline Info & Tech
By Fineline Cube