Ionis announces additional results from zilganersen study in AxD

Ionis Pharmaceuticals (IONS) announced additional results from the pivotal study of zilganersen in children and adults living with Alexander disease, a rare, progressive and often fatal neurological condition with no approved disease-modifying treatments. These findings, which will be presented today at the 2026 American Academy of Neurology annual meeting, build on previously reported positive topline data and provide a more comprehensive view of treatment effect across multiple clinically meaningful domains. The study met its primary endpoint in individuals greater than or equal to5 years of age, with zilganersen 50 mg demonstrating statistically significant and clinically meaningful stabilization of gait speed as assessed by the 10-Meter Walk Test, compared to control at Week 61. The 10MWT is a commonly used measure of gross motor function in neurologic disease. New data from the Gross Motor Function Measure-88, a well-established motor endpoint, supports the primary outcome of the study by demonstrating that treatment with zilganersen may improve gross motor function in younger children, compared to control. Key secondary endpoint results from patient/caregiver- and clinician-reported outcome assessments consistently favored zilganersen. Zilganersen demonstrated favorable safety and tolerability. The pivotal Phase 1-3 study of zilganersen included 53 people with AxD aged 2 to 53 years. Results presented today are from the 60-week double-blind, randomized controlled treatment period of the ongoing trial. Zilganersen met the primary endpoint in patients greater than or equal to5 years, resulting in statistically significant and clinically meaningful stabilization of gait speed on the 10MWT at Week 61 compared to control. Additionally, results from the GMFM-88 in children 2-4 years of age support that zilganersen may improve gross motor function at Week 61 compared to control. Key secondary endpoints favored zilganersen over control: Key secondary endpoints evaluated the disease’s heterogeneous presentation through assessments focused on the individual’s most bothersome AxD symptom and their overall health. Across these measures, outcomes favored zilganersen-treated individuals, with more reporting improvement or no change and fewer reporting worsening compared to control. Most Bothersome Symptom: In the zilganersen group, 32% of patients rated their most bothersome symptom as “much better” compared to 0% on control. Only 5% of patients receiving zilganersen rated their most bothersome symptom as “much worse” compared to 31% on control. Patient Global Impression of Severity: In the zilganersen group, 83% of patients reported improvement or no change in overall disease severity compared to 76% on control. Only 17% of patients receiving zilganersen reported worsening compared to 24% on control. Patient Global Impression of Change: In the zilganersen group, 21% of patients reported feeling “much better” overall compared to 0% on control. Only 4% of patients receiving zilganersen reported feeling “much worse” compared to 18% on control. Clinical Global Impression of Change: Clinicians rated 75% of patients receiving zilganersen as improved or “no change” compared to 47% on control. Clinicians rated 25% of patients receiving zilganersen as “a little worse” and 0% as “much worse” compared to 41% as “a little worse” and 12% as “much worse” on control. Results from additional secondary and exploratory endpoints assessing communication, swallowing, gastrointestinal and autonomic symptoms, consistently support that zilganersen may have a positive impact across AxD symptoms. In an exploratory analysis, zilganersen reduced plasma GFAP levels by 33.6% at Week 61 compared to control, consistent with its mechanism of targeting GFAP RNA in the central nervous system. Zilganersen demonstrated a favorable safety and tolerability profile, with most adverse events mild or moderate in severity. Serious treatment-emergent adverse events occurred less frequently in the zilganersen group compared to control. Zilganersen is currently under Priority Review by the U.S. Food and Drug Administration with a Prescription Drug User Fee Act action date of September 22, 2026.