FDA approves zilganersen as first treatment for Alexander disease

The FDA has approved Zanvastro (zilganersen), the first approved treatment for Alexander disease, for pediatric and adult patients. The rare, progressive neurological disorder results from mutations affecting glial fibrillary acidic protein (GFAP), which accumulates in brain support cells. Zilganersen is an antisense oligonucleotide that reduces GFAP production and is administered into the spinal canal every three months. Approval was granted to Ionis Pharmaceuticals, Inc.

Efficacy and safety were evaluated in a multicenter, randomized controlled study (NCT04849741) involving 49 patients aged 2 years and older, plus an open-label substudy of four children younger than 2 years. Among patients aged 5 years and older with measurable walking difficulties at baseline, treated patients had significantly better walking speed at 61 weeks than those receiving no treatment. Treated children aged 2–4 years improved on a broader motor-skills assessment, while controls declined. The announcement did not provide effect sizes or numerical statistical results.

Evidence in children younger than 2 years was limited and lacked a concurrent control group. Extension of the indication to infancy relied on pharmacokinetic modeling and safety observations in younger and older children. Common adverse effects include vomiting, back pain, cough, headache, and post-lumbar puncture syndrome. Aseptic meningitis has been reported; patients and caregivers should report compatible symptoms. Clinicians should consult the full prescribing information for treatment decisions.