Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) has reported positive topline results from a pivotal study of Zilganersen in children and adults with Alexander disease (AXD), a rare and often fatal neurological condition that currently has no approved disease-modifying treatments. The study demonstrated that Zilganersen 50 mg showed statistically significant and clinically meaningful stabilization on the primary endpoint of gait speed as assessed by the 10-meter walk test (10MWT) compared to the control at week 61 (mean difference 33.3%, p=0.0412).
Moreover, Zilganersen demonstrated consistent benefit in key secondary endpoints, including 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. This marks the first time an investigational medicine has shown a positive disease-modifying impact in AXD.
The study enrolled 54 participants with AXD between the ages of 1.5 and 53 years across 13 sites in eight countries. Most participants were children, reflecting the early onset and severe progression of AXD in pediatric populations. The primary endpoint is the percent change from baseline in gait speed as assessed by the 10MWT at the end of the double-blind treatment period.
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.
The company 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. Detailed data will be presented at an upcoming medical conference.
Zilganersen, an investigational antisense oligonucleotide medicine, is designed to stop the production of excess glial fibrillary acidic protein (GFAP) that accumulates due to disease-causing variants in the GFAP gene. In 2020, the U.S. FDA granted Zilganersen orphan drug designation and rare pediatric designation, and the European Medicines Agency (EMA) granted Zilganersen orphan drug designation in 2019.
The market has reacted to these announcements by moving the company's shares -1.18% to a price of $61.01. Check out the company's full 8-K submission here.
