Ionis Reports Positive Results from Pivotal Study in Rare and Fatal Neurological Disease

Rare Daily Staff

Ionis Pharmaceuticals said its experimental therapy zilganersen showed, for the first time for any treatment, a positive disease-modifying impact on children and adults with Alexander disease, a rare, progressive, and often fatal neurological condition.

In a pivotal study, zilganersen demonstrated statistically significant and clinically meaningful stabilization on the primary endpoint of gait speed, as assessed by the 10-Meter Walk Test, compared with control at week 61. It also showed consistent benefit in key secondary endpoints.

Zilganersen demonstrated a favorable safety and tolerability profile, with most adverse events mild or moderate in severity. The incidence of serious adverse events was numerically lower in the zilganersen arm compared with the control arm.

Ionis said it plans to apply to the FDA in the first quarter of 2026 for approval to market zilganersen.

Alexander disease (AxD) affects astrocytes, a type of brain cell that supports neurons and oligodendrocytes, including maintaining the myelin sheath that protects nerve fibers. AxD is caused by mutations in the glial fibrillary acidic protein gene and is characterized by progressive neurological deterioration resulting in loss of functional mobility, loss of independence, and the inability to control muscles for large movements, swallowing, and airway protection. Symptoms vary depending on age of onset. AxD usually leads to death within 14 to 25 years after symptoms begin. There are no approved disease-modifying medicines.

Zilganersen is an experimental antisense oligonucleotide medicine being evaluated as a treatment for people with genetically confirmed AxD. It is designed to block production of excess glial fibrillary acidic protein that builds up because of disease-causing variants in the GFAP gene.

The U.S. Food and Drug Administration has granted zilganersen Orphan Drug and Rare Pediatric designations. The European Medicines Agency has also granted the therapy Orphan Drug designation.

“These unprecedented results highlight the potential of zilganersen to create new possibilities for people living with Alexander disease,” said Holly Kordasiewicz, senior vice president of neurology at Ionis.

Photo: Holly Kordasiewicz, senior vice president of neurology at Ionis