Ionis Heads to FDA as Antisense Therapy Aces Pivotal Study in Rare Neurological Disease

Ionis Pharmaceuticals announced positive results from a pivotal Phase I–III study of its investigational antisense therapy, zilganersen, in patients with Alexander disease (AxD), a rare and fatal neurological disorder13.

The study involved 54 mostly pediatric patients, randomized to zilganersen (25-mg or 50-mg) or placebo, with double-blind treatment for 60 weeks followed by an open-label extension13.

Zilganersen significantly improved gait stability and walk speed; patients walked 33.3% faster on average at 61 weeks versus baseline, with a p-value of 0.041213.

The FDA has granted zilganersen Fast Track, Orphan Drug, and Rare Pediatric Disease designations; it also received Orphan Drug designation from the European Medicines Agency23.

Most adverse events in the trial were mild or moderate, and serious adverse events were more common in the placebo group than in the treatment group3.

Ionis plans to submit a new drug application (NDA) to the FDA in Q1 2026 and is considering an expanded patient access program in the U.S.13.

No approved disease-modifying therapies currently exist for Alexander disease, highlighting zilganersen's potential impact for this high unmet medical need12.

If approved, analysts estimate potential U.S. peak sales of $295 million and a 90% market penetration1.

Sources:

1. https://www.biospace.com/drug-development/ionis-heads-to-fda-as-antisense-therapy-aces-pivotal-study-in-rare-neurological-disease

2. https://www.prnewswire.com/news-releases/zilganersen-granted-us-fda-fast-track-designation-for-people-living-with-alexander-disease-302263365.html

3. https://www.fiercebiotech.com/biotech/ionis-rare-neurological-disease-candidate-improves-walk-speed-phase-3-win