FDA Grants Priority Review to Ionis’ Zilganersen for Rare Alexander Disease

Ionis Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for zilganersen, an investigational RNA-targeted therapy for Alexander disease (AxD), granting the application Priority Review with a Prescription Drug User Fee Act (PDUFA) action date set for September 22, 2026.

Alexander disease is a rare, progressive and often fatal neurological disorder with no approved disease-modifying treatments.

Brett Monia, Ph.D., Chief Executive Officer of Ionis, said Alexander disease is a devastating and often fatal neurological condition with no approved disease-modifying treatments. He noted that the FDA’s Priority Review for zilganersen highlights the urgent need for therapies and could accelerate access for patients. If approved, the drug would become the first treatment for Alexander disease and mark Ionis’ first independent commercial launch in neurology.

The NDA submission is supported by results from a global Phase 1–3 randomized, double-blind, controlled trial (NCT04849741) involving 54 participants aged 1.5 to 53 years across 13 sites in eight countries. Participants were randomized in a 2:1 ratio to receive zilganersen or control during a 60-week double-blind treatment period, followed by an open-label extension.

In the pivotal 50 mg dose cohort, administered every 12 weeks, the therapy demonstrated statistically significant stabilization in gait speed compared with control at week 61, measured using the 10-Meter Walk Test (10MWT). The treatment showed a least square mean difference of 33.3% (p=0.0412). Safety and tolerability were favorable, while additional endpoints assessing adaptive function, communication, gastrointestinal symptoms, sleep, and seizures also consistently favored zilganersen.

The therapy also showed consistent improvements across multiple secondary and exploratory endpoints, including patients’ Most Bothersome Symptom (MBS) score, Patient Global Impression of Severity (PGIS), Patient Global Impression of Change (PGIC), and Clinician Global Impression of Change (CGIC).

Zilganersen is an antisense oligonucleotide therapy designed to reduce production of glial fibrillary acidic protein (GFAP). Mutations in the GFAP gene lead to excessive accumulation of this protein in astrocytes, contributing to the neurological damage seen in Alexander disease.

According to Ionis, if approved, zilganersen would become the first disease-modifying therapy for Alexander disease and mark the company’s first independent commercial launch in neurology, expanding its rare neurological disease portfolio.

Alexander disease affects roughly 1 to 3 individuals per million worldwide and typically leads to progressive neurological decline, including impaired mobility, swallowing difficulties, and loss of independence. The disease is often fatal, with many patients dying 14 to 25 years after symptom onset.

Ionis previously received Breakthrough Therapy, Orphan Drug, and Rare Pediatric Disease designations from the FDA for zilganersen, while the European Medicines Agency has also granted the therapy Orphan Drug designation.

Additional data from the pivotal study are expected to be presented at the 2026 American Academy of Neurology (AAN) annual meeting in Chicago.

References

Ionis announces zilganersen New Drug Application for Alexander disease (AxD) accepted by FDA for Priority Review, 23 March 2026, Ionis announces zilganersen New Drug Application for Alexander disease (AxD) accepted by FDA for Priority Review | Ionis Pharmaceuticals, Inc.

A Study to Evaluate the Safety and Efficacy of Zilganersen (ION373) in Patients With Alexander Disease (AxD), ClinicalTrials.gov ID NCT04849741, Study Details | NCT04849741 | A Study to Evaluate the Safety and Efficacy of Zilganersen (ION373) in Patients With Alexander Disease (AxD) | ClinicalTrials.gov