Zilganersen Approved by FDA as First Treatment for People with Alexander Disease

The Food and Drug Administration (FDA) has approved Zanvastro (zilganersen; Ionis Pharmaceuticals, Carlsbad, CA) injection for the treatment of pediatric and adult patients with Alexander disease, making it the first approved therapy for the rare neurologic disorder.

Alexander disease is a progressive disorder caused by mutations affecting glial fibrillary acidic protein (GFAP), leading to abnormal protein accumulation in the central nervous system. The condition affects fewer than 1 in 1 million people and may be associated with seizures, developmental regression, gait impairment, weakness, and increased intracranial pressure.

Zanvastro is an antisense oligonucleotide administered intrathecally once every 3 months by a trained health care professional. The therapy is intended to reduce production of abnormal GFAP before it accumulates and contributes to neurologic injury.

Regulatory and Clinical Details

• The FDA approval covers pediatric and adult patients with Alexander disease.
• The efficacy and safety of Zanvastro were evaluated in a multicenter, randomized, controlled clinical study (NCT04849741) of 49 participants aged 2 years and older, as well as an open label substudy that included 4 participants younger than 2 years.
• In participants aged 5 years and older with measurable walking impairment at baseline, Zanvastro treatment was associated with significantly better walking speed at week 61 compared with no treatment.
• In children aged 2 to 4 years, investigators used a broader motor assessment that included standing, walking, running, and jumping; children treated with Zanvastro improved in this measure, whereas those in the control group declined.
• For participants younger than 2 years, the FDA relied on limited clinical data, pharmacokinetic modeling suggesting comparable drug exposure to older pediatric patients, and safety data from treated infants and older children.
• The most common adverse effects were vomiting, back pain, cough, headache, and post-lumbar puncture syndrome.
• Aseptic meningitis has been reported in patients treated with Zanvastro, and clinicians should review the full prescribing information when considering treatment.

Potential Implications for Clinical Practice

The approval introduces the first disease-targeted therapy for individuals with Alexander disease, a condition that previously had no FDA-approved treatment options.

The broad age range of the indication is notable given the rarity and heterogeneity of Alexander disease. However, the evidence base varies by age group, with more direct controlled efficacy data available in patients aged 2 years and older and more limited data in infants. Treatment decisions will require careful consideration of disease stage, motor function, procedural requirements, adverse effects, and family goals of care.

Zanvastro previously received Orphan Drug, Fast Track, Breakthrough Therapy, Rare Pediatric Disease, and Priority Review Voucher designations.

Source

US Food and Drug Administration. FDA Approves First Drug to Treat Alexander Disease. Published September 3, 2026. Accessed September 8, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-alexander-disease