Ionis Pharmaceuticals' zilganersen, an investigational antisense oligonucleotide medicine, has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of both adult and pediatric patients with Alexander disease (AxD). This designation aims to expedite the development and review of zilganersen, addressing a critical unmet need in this rare and progressive neurological condition.
Alexander disease is an ultra-rare leukodystrophy affecting the brain's white matter, with an estimated incidence of one in one to three million people worldwide. The disease, caused by mutations in the glial fibrillary acidic protein (GFAP) gene, leads to the accumulation of abnormal proteins in cells, resulting in progressive damage to the nervous system. Symptoms vary depending on the age of onset but typically include loss of motor control, swallowing difficulties, and impaired airway protection. The prognosis is grim, with a typical survival of 14 to 25 years post-symptom onset. Currently, treatment options are limited to managing symptoms, as there are no approved therapies that target the underlying cause of AxD.
Zilganersen: A Targeted Approach
Zilganersen (ION373) is designed to reduce the production of GFAP, the protein that accumulates due to disease-causing variants in the GFAP gene. By targeting the root cause of the disease, zilganersen holds promise in slowing or halting the progression of AxD. The FDA previously granted zilganersen Orphan Drug and Rare Pediatric Disease designations, and the European Medicines Agency (EMA) also granted Orphan Drug designation.
Clinical Development and Next Steps
The pivotal Phase 1-3 study of zilganersen has completed enrollment across 13 sites in eight countries. This study (NCT04849741) includes both adult and pediatric patients with AxD. Topline data from this study is anticipated in the second half of 2025. "With no approved treatments available for people living with AxD, receiving this Fast Track designation for zilganersen reflects the seriousness of this ultra-rare disease and the significant unmet need for treatment in this patient population," said Eugene Schneider, M.D., executive vice president and chief clinical development officer at Ionis. "Zilganersen was designed to address the underlying cause of disease and help improve the functioning of people living with AxD. We look forward to a data readout next year and working closely with the FDA to potentially bring forward the first approved AxD treatment."
