FDA approves Zanvastro, first treatment for Alexander disease

FDA has approved Zanvastro (zilganersen) for the treatment of Alexander disease in pediatric and adult patients. The new drug is the first approved treatment for the progressive neurological disorder and the first to target the abnormal protein production that drives it.

Until now, care has focused on managing symptoms as neurologic function declines. The approval provides a treatment directed at the disease process across the age spectrum, from infancy through adulthood.

Alexander disease affects fewer than one in one million people. It is caused by variants in the GFAP gene that lead to excessive production and accumulation of glial fibrillary acidic protein in astrocytes—the cells that support and protect neurons. Over time, astrocyte dysfunction damages the nervous system.

Symptoms may begin in infancy, childhood, or adulthood and vary with age at onset. Manifestations can include seizures, developmental regression, difficulty walking, muscle weakness, cognitive and autonomic dysfunction, and impaired swallowing or airway protection.

Zanvastro is an antisense oligonucleotide, a type of RNA-targeted drug that reduces production of glial fibrillary acidic protein before it can accumulate and cause further neurologic injury. A trained healthcare professional administers the drug as a 50 mg intrathecal injection every 12 weeks.

The approval was supported by a multicenter, randomized, double-blind, controlled phase 1-3 study. FDA evaluated results from 49 patients aged 2 years and older, along with an open-label substudy involving four children younger than 2 years.

Among patients aged 5 years and older who had measurable walking impairment at baseline, those treated with Zanvastro had better walking speed at 61 weeks than those who received no treatment.

Because walking speed is not a reliable measure of progress in younger children, investigators assessed patients aged 2 to 4 years using the Gross Motor Function Measure-88, which evaluates abilities such as standing, walking, running, and jumping. Gross motor function improved among children treated with Zanvastro but declined in the control group.

Direct clinical evidence was limited in children younger than 2 years because of the rarity of Alexander disease and the lack of a concurrent control group. Pharmacokinetic modeling indicated that the approved dose would produce drug exposure similar to that seen in older children. Safety findings from the four patients in the open-label substudy, together with data from older pediatric patients, supported extending the indication to this age group.

The most common adverse reactions, occurring in at least 25% of Zanvastro-treated patients and more frequently than in controls, were vomiting, back pain, cough, headache, and post–lumbar puncture syndrome. Aseptic meningitis has also been reported. If symptoms suggestive of meningitis develop, clinicians should initiate diagnostic evaluation and treatment according to standard care.

The manufacturer expects Zanvastro to become available in the United States in the coming weeks.

Emily Petty, president of End Alexander Disease and the mother of a young boy with the condition, said families have long faced the uncertainty of an Alexander disease diagnosis without any available treatment. “Today’s approval represents a fundamental shift, changing the conversation from ‘How do we manage this disease?’ to ‘How can we treat it?’”

Source: Ionis Pharmaceuticals, Inc. (2026 Sep 3). Zanvastro (zilganersen) approved by the FDA as the first and only disease modifying treatment for Alexander disease (AxD) in pediatric and adult patients; US Food and Drug Administration. (2026 Sep 3). FDA Approves First Drug to Treat Alexander Disease