By improving gait stability, Ionis’ zilganersen could be “potentially disease modifying,” according to analysts at William Blair.
Ionis Pharmaceuticals’ investigational antisense oligonucleotide zilganersen significantly improved gait stability in a pivotal Phase I–III study in the rare neurological condition Alexander disease, clearing the road to the FDA.
In a note to investors on Monday, analysts at William Blair said that these findings position zilganersen as “potentially disease modifying,” which they argued could help the asset’s regulatory case. The high unmet need in Alexander disease (AxD) and the lack of an approved disease-modifying therapy, they said, could be “taken into account by regulators” when evaluating zilganersen’s data package.
Ionis is planning to file a new drug application in the first quarter of 2026 and is looking at the prospect of initiating an expanded patient access program in the U.S., according to the company’s announcement of the data. If approved, William Blair anticipates peak sales of $295 million with a 90% penetration rate in the U.S.
Monday’s readout came from a Phase I–III study, which enrolled 54 patients with AxD, most of whom were children. Participants were randomized on a 2:1 basis to receive either 25-mg or 50-mg of zilganersen, or a placebo control. Double-blind treatment continued for 60 weeks before patients were transitioned into an open-label phase.
Results demonstrated a “statistically significant and clinically meaningful” effect on gait stability, the study’s primary endpoint. This was measured using the 10-meter walk test, which detected a mean improvement of 33% in patients given the higher 50-mg dose.
Ionis on Monday also announced that zilganersen elicited a “consistent favorable” improvement in secondary endpoints, which the biotech argued is “evidence of slowed disease progression, stabilization or improvement.” The biotech has promised to present detailed data from this study at an upcoming scientific congress.
According to William Blair, these details will be important to zilganersen’s market prospects, noting that “the magnitude of improvement in key secondary endpoints as having potential read-through to pricing, if approved,”
AxD is a rare, progressive and often fatal neurological disease that afflicts one patient in one to three million people worldwide. Patients with AxD suffer from progressive neurological disability and the loss of muscle control, mobility and independence.
AxD is caused by alterations to the GFAP gene. Zilganersen treats the condition by reducing the production of the mutated protein, which would otherwise damage brain cells. The FDA has previously granted zilganersen its orphan drug and rare pediatric disease designations.
Monday’s readout comes after Ionis last month won the FDA’s approval for another of its antisense oligonucleotides, Dawnzera, making it the first RNA-targeting prophylactic therapy for hereditary angioedema.
