Zilganersen Improves Functional Mobility in Patients With Alexander Disease

Topline data were announced from a pivotal study evaluating zilganersen in children and adults living with Alexander disease. 

Alexander disease (AxD) is a rare, progressive neurological disease caused by variants in the glial fibrillary acidic protein (GFAP) gene. It is characterized by seizures, muscle stiffness, and developmental delays. Zilganersen is an antisense oligonucleotide designed to block the production of excess GFAP caused by mutations in the GFAP gene. 

The double-blind, randomized, placebo-controlled, phase 1-3 study (ClinicalTrials.gov Identifier: NCT04849741), evaluated the safety and efficacy of zilganersen in 54 participants aged 1.5 to 53 years with AxD and a documented genetic mutation in the GFAP gene. 

Study participants were randomly assigned 2:1 to receive intrathecal zilganersen or placebo once every 12 weeks for a 60 week double-blind treatment period. After the double-blind treatment period, patients transitioned into an open-label treatment period, followed by a 120-week long-term extension phase. The primary endpoint was the percent change from baseline in gait speed as assessed by the 10-Meter Walk Test (10MWT) at the end of the double-blind treatment period.

Findings showed patients treated with zilganersen 50mg demonstrated statistically significant and clinically meaningful improvement from baseline in gait speed, as assessed by the 10MWT, compared with those who received placebo, at week 61 (difference, 33.3%; P =.0412). 

Results also showed improvements in key secondary endpoints (eg, change from baseline in patients’ self-identifier Most Bothersome Symptom score, Patient Global Impression of Severity score, Patient Global Impression of Change score, Clinician Global Impression of Change score). 

Zilganersen was safe and well-tolerated, with most adverse events being mild or moderate. Serious adverse events occurred less frequently in the zilganersen arm vs the placebo arm. 

“These unprecedented results highlight the potential of zilganersen to create new possibilities for people living with Alexander disease, a devastating, progressive and often fatal condition that most commonly begins in early childhood and can take away fundamental functions like walking, speaking and swallowing,” said Holly Kordasiewicz, PhD, senior vice president of neurology, Ionis. 

According to Ionis, a New Drug Application for AxD is expected in the first quarter of 2026. A potential Expanded Access Program is also being evaluated by the Company.

This article originally appeared on MPR