FDA Approves Zanvastro, First Therapy for Alexander Disease

The Food and Drug Administration on Thursday approved Zanvastro, or zilganersen, the first treatment ever cleared for Alexander disease, a rare genetic neurological disorder that until now had no approved therapies. The approval covers pediatric and adult patients, from infancy through adulthood, and was granted to Ionis Pharmaceuticals Inc.

The decision marks a milestone for patients with a disease that is both progressive and ultra-rare. Alexander disease is a leukodystrophy, a disorder that damages the brain’s white matter, and is caused by harmful variants in the GFAP gene. The condition leads to a toxic buildup of glial fibrillary acidic protein, or GFAP, in brain cells called astrocytes, driving worsening neurological problems over time. The FDA says Alexander disease affects fewer than 1 in 1 million people. Before Zanvastro, treatment was limited to supportive care aimed at managing symptoms.

Zilganersen is designed to target the disease’s underlying biology rather than just its complications. It is an antisense oligonucleotide, a type of genetic medicine built to reduce production of abnormal GFAP. The drug is given by injection into the spinal canal and is administered every three months, according to the FDA.

The approval was backed by a multicenter randomized controlled Phase 1-3 study that enrolled 49 pediatric and adult patients age 2 and older, along with an open-label substudy of four patients younger than 2. In the main older-child and adult group, the FDA said patients who received zilganersen had significantly better walking speed at 61 weeks than controls, based on the 10-Meter Walk Test. In practical terms, the agency said the findings showed improved or stabilized walking speed in the studied group, an important measure in a disease that can steadily impair movement and function.

Evidence was more limited for children younger than 2. For that group, the FDA said approval relied on pharmacokinetic modeling — an approach that estimates how a drug behaves in the body — together with safety data from the four patients younger than 2 who were included in the study. That allowed the agency to extend the indication across the full age range, while acknowledging that direct trial data in the youngest patients were limited.

The FDA said the most common adverse reactions seen with Zanvastro were vomiting, back pain, cough, headache and post-lumbar puncture syndrome, a complication that can occur after a spinal tap or similar procedure. The agency also said aseptic meningitis, an inflammation of the membranes around the brain and spinal cord not caused by bacteria, has been reported. Patients and caregivers should alert health care providers if symptoms consistent with meningitis develop, the FDA said.

Zilganersen also received several expedited regulatory designations during development, including Orphan Drug, Fast Track, Breakthrough Therapy and Rare Pediatric Disease status, reflecting both the severity of the condition and the lack of available options.

“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 in the FDA’s Center for Drug Evaluation and Research. “Today’s approval is a landmark moment for this community, offering the first therapy that addresses the underlying cause of this rare and serious disease.”