Zilganersen Receives FDA Priority Review Designation for Alexander Disease
Key Takeaways
- The FDA granted Priority Review designation to zilganersen for the treatment of Alexander disease.
- The investigational antisense oligonucleotide therapy demonstrated improvement in gait speed compared with controls at 60 weeks.
- Zilganersen would be the first disease-modifying therapy for Alexander disease if approved.
The Food and Drug Administration (FDA) has granted Priority Review designation to the New Drug Application (NDA) for zilganersen (ION373; Ionis Pharmaceuticals, Carlsbad, CA), an investigational antisense oligonucleotide for the treatment of children and adults with Alexander disease (AxD). The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of September 22, 2026. If approved, zilganersen would be the first disease-modifying therapy for AxD.
AxD is a rare, genetic, and often fatal astrocytopathy characterized by an accumulation of glial fibrillary acidic protein (GFAP) that leads to progressive neurological deterioration including the loss of functional mobility and independence and an inability to control muscles for large movements, swallowing, and airway protection. Zilganersen is designed to inhibit the production of excess GFAP.
The NDA and Priority Review designation were based on results from a phase 1-3 trial (NCT04849741). The global, multicenter, randomized, double-blind study enrolled 54 participants (aged 1.5 to 53 years) across 13 sites in 8 countries. Participants were randomized 2:1 to zilganersen or control for 60 weeks, and the trial evaluated 25-mg and 50-mg cohorts, with 50 mg every 12 weeks designated as the pivotal dose cohort. The primary end point was percent change from baseline in gait speed on the 10-Meter Walk Test (10MWT), and secondary measures included Most Bothersome Symptom (MBS), Patient Global Impression of Severity (PGIS), Patient Global Impression of Change (PGIC), and Clinician Global Impression of Change (CGIC) scores.
Zilganersen 50 mg showed statistically significant improvement in the primary end point, with a least squares mean difference of 33.3% in gait speed versus control at week 61 (P=.0412). Safety and tolerability were also favorable, and key secondary and exploratory outcomes, including adaptive function, communication, gastrointestinal symptoms, sleep, and seizures, consistently favored zilganersen.
Source
Ionis. Ionis announces zilganersen New Drug Application for Alexander disease (AxD) accepted by FDA for Priority Review. Press release. March 23, 2026. Accessed March 30, 2026. https://ir.ionis.com/news-releases/news-release-details/ionis-announces-zilganersen-new-drug-application-alexander