Pivotal Zilganersen Study Meets Primary Endpoint; FDA Decision Expected September 22, 2026

At the 2026 American Academy of Neurology Annual Meeting, Ionis Pharmaceuticals presented new data from the pivotal Phase 1–3 study of zilganersen — the investigational RNA-targeted medicine designed to treat Alexander Disease by reducing the overproduction of GFAP, the underlying cause of AxD.

The study met its primary endpoint.

Participants ages 5 and older who received zilganersen showed statistically significant and clinically meaningful stabilization of gait speed at Week 61 compared to control, as measured by the 10-Meter Walk Test (p=0.041). In children ages 2–4, results from the Gross Motor Function Measure (GMFM-88) support that zilganersen may improve gross motor function. Patient-, caregiver-, and clinician-reported outcomes consistently favored zilganersen across measures of most bothersome symptom, overall disease severity, and clinician-rated change. Plasma GFAP levels were reduced by 33.6% at Week 61, consistent with zilganersen's mechanism of action. Safety and tolerability were favorable, with serious adverse events occurring less frequently in the zilganersen group than in control.

The pivotal study enrolled participants ages 2 to 53 years across 13 sites in eight countries. Dr. Amy Waldman, pediatric neurologist and lead investigator at Children's Hospital of Philadelphia, noted that the consistent pattern across multiple clinically meaningful measures demonstrates zilganersen's potential to change the trajectory of Alexander Disease.

Zilganersen is currently under Priority Review by the U.S. Food and Drug Administration. The PDUFA action date — the date by which the FDA is expected to make a decision — is September 22, 2026.

For a community that has lived without any approved disease-modifying treatment, these data mark a meaningful step forward. There is still a road ahead: regulatory review in the U.S., continued work on global access pathways, and sustained advocacy for every family watching and waiting. But the evidence is now in front of us, and the path is clearer than it has ever been.

To every patient, every family, every investigator, and every advocate who made this research possible — thank you. You are the reason this day happened.

We will continue to share updates as we receive them.

Read the full announcement from Ionis here.