Ionis Receives Breakthrough Therapy Designation for Zilganersen for Alexander Disease
Wednesday, December 03, 2025
Ionis Pharmaceuticals has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to zilganersen, a potential treatment for Alexander disease (AxD).
Zilganersen is an investigational antisense oligonucleotide designed to reduce the production of excess glial fibrillary acidic protein (GFAP). Elevated GFAP levels result from genetic variants linked to Alexander disease. The medicine has previously received Orphan Drug and Rare Paediatric Disease designations from the FDA, in addition to Orphan Drug designation from the European Medicines Agency (EMA).
Alexander disease is a rare neurological disorder affecting approximately one in one to three million people globally. It involves progressive deterioration of neurological function linked to disease-causing variants in the GFAP gene. The condition mainly affects astrocytes—cells responsible for supporting neurons and maintaining the myelin sheath.
The disease can vary in severity depending on age of onset but commonly leads to progressive loss of mobility and independence. Difficulty with swallowing and airway protection may also develop. Most individuals experience fatal disease progression within 14 to 25 years of symptom onset. Currently, there are no approved therapies capable of modifying the course of the disease.
Breakthrough Therapy designation is granted to medicines that target serious or life-threatening conditions and show early evidence of potential clinical benefit over current treatment options. This status aims to accelerate development and regulatory review.
The designation is based on topline results from a pivotal study evaluating zilganersen in both children and adults with AxD. In the trial, the 50 mg dose showed statistically significant improvement and clinical benefit in gait speed using the 10-Metre Walk Test at week 61 when compared with the control arm. Safety and tolerability findings were considered favourable. The medicine also demonstrated benefits across key secondary measures.
Ionis has noted that the advancement of zilganersen represents progress in addressing a major unmet need for this rare condition.
The company is preparing to submit a New Drug Application (NDA) to the U.S. FDA in the first quarter of 2026 and is planning to open an Expanded Access Programme in the United States.
Source: ionis.com
