Ionis Pharmaceuticals’ antisense oligonucleotide zilganersen (for Alexander disease) is now awaiting an FDA decision after a pivotal phase 1–3 study met its primary endpoint but missed key secondary goals. At AAN 2026, the company presented data from its Phase I-III trial (NCT04849741), reporting statistically significant gait speed stabilization in individuals 5 years and older. However, the therapy failed to achieve a statistically significant reduction in the “most bothersome symptom” (MBS) endpoint. Ionis described the clinical picture as mixed—while gait stabilization was achieved and many patients reported improvements or no change in severity, the missed secondary outcome remained central to regulators’ and clinicians’ assessment. Given the lack of approved disease-modifying options for Alexander disease, Ionis’ interpretation suggests the setback may not derail approval. The FDA decision timing will be watched closely, especially for how the agency weighs primary functional measures against secondary symptom impacts in an ultra-rare setting.