Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) has just released positive topline results from a pivotal study of Zilganersen, an investigational medicine for treating Alexander disease (AXD), a rare and often fatal neurological condition with no approved disease-modifying treatments. Zilganersen 50 mg demonstrated statistically significant and clinically meaningful stabilization on the primary endpoint of gait speed as assessed by the 10-meter walk test (10MWT) compared to control at week 61, with a mean difference of 33.3% and a p-value of 0.0412.
The study enrolled 54 participants with AXD between the ages of 1.5 and 53 years across 13 sites in eight countries. Most participants in the study were children, reflecting the early onset and severe progression of AXD in pediatric populations. Participants were randomized in a 2:1 ratio to receive Zilganersen or control for a 60-week double-blind treatment period. The study included two dose cohorts, 25 mg and 50 mg, with the 50 mg dose cohort analyzed as the pivotal dose cohort, with dosing every 12 weeks.
In addition to achieving the primary endpoint, Zilganersen demonstrated consistent favorable trends across key secondary endpoints, including a change from baseline in patients' self-identified most bothersome symptom (MBS) score, patient global impression of severity (PGIS) score, patient global impression of change (PGIC), and clinician global impression of change (CGIC) score.
Zilganersen also demonstrated a favorable safety and tolerability profile, with most adverse events (AE) being mild or moderate in severity. The incidence of serious adverse events (SAEs) was numerically lower in the Zilganersen arm as compared to the control arm.
Ionis plans to submit a new drug application (NDA) to the U.S. Food and Drug Administration in Q1 2026 and is evaluating the potential to initiate an expanded access program (EAP) in the U.S.
Zilganersen is designed to stop the production of excess glial fibrillary acidic protein (GFAP) that accumulates because of disease-causing variants in the GFAP gene. In 2020, the U.S. Food and Drug Administration (FDA) granted Zilganersen orphan drug designation and rare pediatric designation.
These positive results mark the first time an investigational medicine has shown a positive disease-modifying impact in AXD, offering hope for people living with this devastating condition. Ionis aims to bring this potential treatment forward for individuals and families in urgent need and further underscored the strength of its proven platform to address severe neurological diseases. Following these announcements, the company's shares moved 0.46%, and are now trading at a price of $61.29. Check out the company's full 8-K submission here.
