The US Food and Drug Administration (FDA) has approved zilganersen (Zanvastro), a glial fibrillary acidic protein (GFAP)-directed antisense oligonucleotide indicated for the treatment of Alexander disease in pediatric and adult patients. Mechanism of Action Zilganersen causes degradation of GFAP pre-mRNA by binding to GFAP pre-mRNA, resulting in reduced GFAP protein synthesis. Clinical Evidence Supporting Approval The efficacy of zilganersen was evaluated in a multicenter study involving pediatric and adult patients with Alexander disease.

The main study enrolled 49 patients aged 2 to 65 years, with an additional open-label substudy enrolling 4 patients younger than 2 years. Key findings at Week 61 included: Gait speed: −2.1% with zilganersen 50 mg vs −35.4% with control Adjusted least-squares mean difference: 33.3% In patients aged 2–4 years, zilganersen showed an observed improvement…