For Immediate Release: September 3, 2026
The U.S. Food and Drug Administration has approved Zanvastro (zilganersen) injection for the treatment of Alexander disease in pediatric and adult patients. It is the first FDA-approved treatment for this rare neurological disorder and the first therapy to directly target the protein buildup that drives the disease.
Alexander disease is a rare, progressive neurological condition caused by mutations in the gene producing glial fibrillary acidic protein (GFAP). Abnormal GFAP accumulates in the brain's supportive cells, damaging the nervous system over time. Affecting fewer than 1 in a million people, the disease can cause seizures, loss of developmental milestones, difficulty walking, muscle weakness, and increased intracranial pressure.
"For patients with Alexander disease and their families, there have been no approved treatment options — only supportive care while the disease progresses," said Dr. Emily Freilich, Director of the Division of Neurology I at the FDA. "Today's approval is a landmark moment, offering the first therapy that addresses the underlying cause of this rare and serious disease."
Mechanism of Action
Zanvastro is an antisense oligonucleotide that reduces production of abnormal GFAP protein before it can accumulate. It is administered via injection into the spinal canal once every three months by a trained healthcare professional.
Clinical Evidence
Efficacy and safety were evaluated in a multicenter, randomized, controlled study (NCT04849741) enrolling 49 patients aged 2 years and older, plus an open-label substudy of 4 patients under 2 years.
In patients aged 5 years and older with measurable walking difficulties at baseline, those treated with Zanvastro showed significantly better walking speed at 61 weeks compared to untreated controls. In children aged 2 to 4 years, where walking speed is unreliable as a measure, a broader motor skills assessment (standing, walking, running, jumping) was used. Treated children improved while controls declined.
For patients under 2 years, pharmacokinetic modeling confirmed expected drug levels comparable to older children at the same dose, supported by safety data from the four youngest patients.
Safety Profile
Most common side effects include vomiting, back pain, cough, headache, and post-lumbar puncture syndrome. Aseptic meningitis has been reported; patients should inform their healthcare provider if meningitis symptoms develop.
Regulatory Designations
Zanvastro received Orphan Drug, Fast Track, Breakthrough Therapy, and Rare Pediatric Disease Priority Review Voucher designations.
The approval was granted to Ionis Pharmaceuticals, Inc.
