Ionis Reports Positive New Data on Experimental Alexander Disease Therapy

Rare Daily Staff

Ionis Pharmaceuticals released new data showing its experimental drug zilganersen for Alexander disease helped stabilize walking ability and eased symptoms in children and adults with the ultra-rare neurological disorder.

The new results were presented at the 2026 American Academy of Neurology Annual Meeting. Zilganersen is under priority review at the U.S. Food and Drug Administration, with a decision expected September 22, 2026.

Alexander disease is a rare, progressive, often fatal neurological disorder that affects star-shaped support cells in the brain called astrocytes. It is estimated to affect roughly 1 out of every 1 million to 3 million people worldwide, usually leading over time to loss of walking ability, loss of independence, and difficulty controlling muscles needed for large movements, swallowing, and protecting the airway. Symptoms and age of onset vary, but the disease typically results in death within about 14 to 25 years after symptoms begin, and there are currently no approved medicines that modify the course of the disease.

Zilganersen is an experimental RNA-targeted medicine designed to reduce production of excess GFAP, a protein that builds up in the brain because of disease-causing variants in the GFAP gene. The FDA has granted zilganersen Breakthrough Therapy, Orphan Drug, and Rare Pediatric Disease designations, and the European Medicines Agency has also awarded it Orphan Drug status for Alexander disease.

In a pivotal phase 1-3 trial of 53 people ages 2 to 53, zilganersen met its main goal in participants 5 and older by stabilizing gait speed over roughly 60 weeks, as measured by the 10-Meter Walk Test, compared with a control group. Ionis reported a least square mean difference in gait speed of 33.3 percent at week 61 in favor of the higher 50-milligram dose, which the company described as both statistically significant and clinically meaningful.

Additional data in younger children suggested potential gains rather than just stabilization. Among those 2 to 4 years old, scores on a standard motor scale called the Gross Motor Function Measure-88 improved by 22.9 points on average relative to control at week 61, according to Ionis.

Across several patient- and clinician-reported measures of overall health and most bothersome symptoms, more people on zilganersen reported feeling “much better” or stable, and fewer reported worsening, than in the control group. Patients taking zilganersen were more likely to say their single most troubling symptom had improved, with nearly one-third in that group rating it “much better” compared with none in the control arm. On global impression scales that ask patients and clinicians to rate overall disease severity and change, most people receiving the drug were scored as improved or unchanged, while worsening was more common among those on control.

The drug’s safety profile was described as favorable, with most side effects mild or moderate in intensity. Serious treatment-emergent adverse events occurred less often among people receiving zilganersen at either 25 or 50 milligrams than in the pooled control group over the double-blind period, Ionis said.

“These results mark a meaningful step forward for families who have waited so long for innovation in Alexander disease,” said Amy Waldman, pediatric neurologist and lead investigator for the zilganersen study at Children’s Hospital of Philadelphia. “Taken together, the consistent pattern across multiple clinically meaningful measures demonstrates that zilganersen has the potential to change the trajectory of this devastating disease.”