FDA Approves Zilganersen, First Treatment for Alexander Disease

According to a new announcement, the FDA has approved zilganersen injection, marketed as Zanvastro (Ionis), for the treatment of Alexander disease in pediatric and adult patients.¹ With the decision, Zanvastro becomes the first FDA-approved treatment for Alexander disease and the first therapy to directly target the protein buildup driving the disease.¹

"For patients with Alexander disease and their families, there have been no approved treatment options, only supportive care while the disease progresses," Emily Freilich, MD, director of the Division of Neurology I in the FDA's Center for Drug Evaluation and Research, said in a statement.¹ Freilich said the approval is a landmark moment for this community, offering the first therapy that addresses the underlying cause of this rare and serious disease.

Alexander disease is a rare, progressive neurological disorder caused by mutations in the gene that produces glial fibrillary acidic protein (GFAP). When this protein is abnormal, it accumulates in the brain's supportive cells, damaging the nervous system over time, and the disease affects fewer than 1 in a million people, causing seizures, loss of developmental milestones, difficulty walking, muscle weakness, and increased intracranial pressure.

Mechanistically, Zanvastro is an antisense oligonucleotide that works by reducing production of the abnormal GFAP protein before it can accumulate and cause further damage, administered as an injection into the spinal canal every 3 months by a trained health care professional.

Trial evaluated patients across a wide age range

The efficacy and safety of zilganersen were evaluated in a multicenter, randomized, controlled clinical study (NCT04849741) enrolling 49 pediatric and adult patients with Alexander disease 2 years of age and older, along with an open-label substudy of 4 patients younger than 2 years.² Because Alexander disease is rare and can affect patients across a wide range of ages, the FDA evaluated the available evidence to support an indication covering patients from infancy through adulthood.¹

In patients 5 years and older with measurable difficulties walking at baseline, those treated with zilganersen showed significantly better walking speed at 61 weeks compared with those who received no treatment. In children aged 2 to 4 years, where walking speed is not a reliable measure of progress, a broader motor skills assessment, including standing, walking, running, and jumping, was used instead, and treated children showed improvement on this measure while the control group declined.¹

Evidence in infants relied on pharmacokinetic modeling

For patients younger than 2 years, direct clinical trial data were limited by the rarity of the disease and the lack of a concurrent control group. Pharmacokinetic modeling showed drug levels in this age group are expected to be similar to those seen in older children at the same dose, an observation supported by safety data from the 4 patients younger than 2 years treated in the study, along with safety data from older pediatric patients. This approach supported extending the indication to the youngest patients while maintaining the evidentiary standards required for approval.

The most common side effects of this newly FDA-approved therapy are vomiting, back pain, cough, headache, and post-lumbar puncture syndrome. Aseptic meningitis has been reported in patients treated with Zanvastro, and patients and caregivers should inform their health care provider if symptoms consistent with meningitis develop. Previously, zilganersen had received orphan drug, fast track, breakthrough therapy, and rare pediatric disease and priority review voucher designations.¹

REFERENCES
1. US Food and Drug Administration. FDA Approves First Drug to Treat Alexander Disease. News release. Published September 3, 2026. Accessed September 3, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-alexander-disease
2. ClinicalTrials.gov. A Study of Zilganersen in Pediatric and Adult Participants With Alexander Disease. NCT04849741. Accessed September 3, 2026. https://clinicaltrials.gov/study/NCT04849741