The U.S. Food and Drug Administration has approved Zanvastro (zilganersen) injection for treating pediatric and adult patients with Alexander disease. The approval makes Zanvastro the first FDA-approved treatment for Alexander disease and the first therapy designed to directly target the protein buildup responsible for driving the disease.
“For patients with Alexander disease and their families, there have been no approved treatment options — only supportive care while the disease progresses,” said Emily Freilich, M.D., 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,” she added.
Alexander disease is a rare and progressive neurological disorder linked to mutations in the gene responsible for producing glial fibrillary acidic protein (GFAP). When the protein is abnormal, it builds up in the brain’s supportive cells and progressively damages the nervous system. The disease affects less than 1 in a million people and can result in serious, potentially life-threatening complications, including seizures, loss of developmental milestones, difficulty walking, muscle weakness, and increased pressure in the brain.
Zanvastro Targets Abnormal GFAP Protein
Zanvastro belongs to a class of medicines known as antisense oligonucleotides. The treatment works by reducing the production of abnormal GFAP protein before it has the opportunity to accumulate and cause additional damage. The medicine is administered through an injection into the spinal canal once every three months, with the procedure performed by a trained healthcare professional.
The safety and efficacy of Zanvastro were assessed through a multicenter, randomized, controlled clinical study (NCT04849741), which enrolled 49 pediatric and adult patients with Alexander disease who were 2 years of age and older. The evaluation also included an open-label substudy involving 4 patients less than 2 years of age. Given the rarity of Alexander disease and the broad age range across which it can occur, the FDA considered the available evidence to support an indication extending from infancy through adulthood.
Clinical Study Shows Improvement in Motor Function
Among patients aged 5 years and older who had measurable walking difficulties at baseline, those receiving Zanvastro demonstrated significantly better walking speed at 61 weeks than patients who received no treatment. For children aged 2 to 4 years, walking speed was not considered a reliable way to measure progress. Instead, researchers used a broader assessment of motor skills covering standing, walking, running, and jumping. Children receiving Zanvastro improved on this assessment, while children in the control group declined.
For patients under 2 years of age, direct clinical trial evidence was limited because of the rarity of the disease and the absence of a concurrent control group. Pharmacokinetic modeling indicated that drug levels among patients in this age group were expected to be similar to those observed in older children receiving the same dose. The finding was further supported by safety information from four patients under 2 years of age who were treated in the study, along with safety data from older pediatric patients. This evidence supported extending the indication to the youngest patients while maintaining the evidentiary standards required for approval.
Safety Profile and FDA Designations
The most common side effects associated with Zanvastro include vomiting, back pain, cough, headache, and post-lumbar puncture syndrome. Patients and caregivers have been advised to notify their healthcare provider if symptoms consistent with meningitis occur, as aseptic meningitis has been reported among patients treated with Zanvastro. Patients and healthcare providers should carefully review the full prescribing information when considering treatment decisions.
Zanvastro received Orphan Drug, Fast Track, Breakthrough Therapy, and Rare Pediatric Disease and Priority Review Voucher designations. These designations reflect the serious and rare nature of Alexander disease and FDA’s commitment to rare disease drug development. The approval of Zanvastro for the treatment of Alexander disease was granted to Ionis Pharmaceuticals, Inc.
