The U.S. Food and Drug Administration has approved Zanvastro (zilganersen) injection for the treatment of Alexander disease in pediatric and adult patients. This approval marks the first time the agency has cleared a therapy for this condition, making Zanvastro the first drug to directly target the underlying cause of the disease.
Alexander disease is a rare, progressive neurological disorder caused by mutations in the gene that produces glial fibrillary acidic protein (GFAP). The abnormal accumulation of this protein in the brain's supportive cells leads to nervous system damage. The disease affects less than 1 in a million people and can cause seizures, loss of developmental milestones, difficulty walking, muscle weakness, and increased brain pressure.
Zanvastro is an antisense oligonucleotide designed to reduce the production of abnormal GFAP protein before it accumulates. It is administered as an injection into the spinal canal every three months by a trained healthcare professional. The approval was granted to Ionis Pharmaceuticals, Inc.
The efficacy of the drug was evaluated in a multicenter, randomized, controlled clinical study (NCT04849741) enrolling 49 pediatric and adult patients aged 2 years and older, along with an open-label substudy of 4 patients under 2 years of age. In patients aged 5 and older who had walking difficulties at baseline, those treated with Zanvastro showed significantly better walking speed at 61 weeks compared to the control group. In children aged 2 to 4 years, treated patients showed improvement in motor skills assessments, while those in the control group declined.
Common side effects of Zanvastro include vomiting, back pain, cough, headache, and post-lumbar puncture syndrome. Patients are advised to inform their healthcare provider if they develop symptoms consistent with meningitis, as aseptic meningitis has been reported.
The drug received Orphan Drug, Fast Track, Breakthrough Therapy, Rare Pediatric Disease, and Priority Review Voucher designations from the FDA.
