Ionis Pharmaceuticals is eyeing a new rare disease approval after its antisense oligonucleotide zilganersen successfully improved mobility in patients with the neurological condition Alexander disease.
Of the 54 patients enrolled in a phase 1-3 trial, those given zilganersen could walk an average of 33.3% faster compared with baseline after 61 weeks, Ionis announced Sept. 22.
The result squeaked into statistical significance with a p-value of 0.0412. Study participants received zilganersen or placebo every 12 weeks through Week 49, and their walk speed was measured 61 weeks after treatment began.
At 60 weeks, eligible patients transitioned to an open-label extension period in which they continued receiving zilganersen.
Most adverse events were mild or moderate, Ionis added, with more serious adverse events occurring in the placebo arm than in the treatment arm of the trial.
Ionis intends to submit zilganersen for FDA approval in the first quarter of 2026, the California biotech said in the release, and is also looking into launching an expanded access program. The asset had previously snagged orphan drug and rare pediatric disease designations from the FDA as well as an orphan drug designation from the European Medicines Agency.
Zilganersen treatment also led to positive changes in several secondary endpoints, Ionis said, though the company did not disclose whether these results were statistically significant. This includes improvements in patients’ self-reported most bothersome symptom and impression of their own disease severity as well as their clinicians' impressions of their symptom improvement.
This is the first time an investigational therapy has shown a disease-modifying effect in Alexander disease, according to the release.
“These unprecedented results highlight the potential of zilganersen to create new possibilities for people living with Alexander disease,” Holly Kordasiewicz, Ph.D., Ionis’ senior vice president of neurology, said in the release. “These data demonstrate the promise of zilganersen to potentially transform the future treatment landscape for this condition and reinforce the power of our technology to address neurological diseases by directly targeting the underlying cause.”
In Alexander disease, mutations in the gene that makes glial fibrillary acidic protein (GFAP) cause the protein to build up in the brain’s white matter, damaging the protective covering that shields nerve cells.
This damage leads to physical and intellectual impairment as well as seizures and other symptoms like difficulty speaking and swallowing, depending on when the disease manifests.
In some patients, the disease appears while still in the womb, with symptoms present right at birth.
Zilganersen is designed to bind to the mRNA made from the GFAP gene to prevent it from being turned into protein, halting the toxic buildup that causes Alexander disease.