Ionis Pharmaceuticals' zilganersen, an investigational antisense oligonucleotide medicine, has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of both children and adults suffering from Alexander disease (AxD). This rare, progressive, and ultimately fatal neurological disorder currently has no approved treatments, making zilganersen a potential breakthrough therapy. Topline data from the pivotal Phase 1-3 study are anticipated in the second half of 2025.
Addressing an Unmet Need in Alexander Disease
Alexander disease (AxD) is an ultra-rare leukodystrophy affecting an estimated one in one to three million people worldwide. The disease is characterized by the accumulation of abnormal glial fibrillary acidic protein (GFAP) in cells, leading to progressive damage to the nervous system. Symptoms can manifest throughout life, resulting in loss of independence and impaired muscle control, with death typically occurring 14-25 years after symptom onset. Current treatments are limited to managing symptoms, highlighting the urgent need for targeted therapies.
Zilganersen: A Potential Disease-Modifying Therapy
Zilganersen (ION373) is designed to address the root cause of AxD by reducing the production of GFAP. The drug is an antisense oligonucleotide that targets the GFAP gene, aiming to prevent the build-up of abnormal proteins in cells. Eugene Schneider, M.D., executive vice president and chief clinical development officer at Ionis, stated that the Fast Track designation "reflects the seriousness of this ultra-rare disease and the significant unmet need for treatment." He added, "Zilganersen was designed to address the underlying cause of disease and help improve the functioning of people living with AxD."
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. Zilganersen has previously been granted Orphan Drug designation and Rare Pediatric Disease designation by the FDA, as well as Orphan Drug designation by the European Medicines Agency (EMA).
Fast Track Designation: Streamlining Development and Review
The FDA's Fast Track designation is intended to accelerate the development and review of drugs that demonstrate the potential to treat serious conditions and address unmet medical needs. This designation provides Ionis with opportunities for more frequent meetings with the FDA to discuss the development plan and data needed to support approval. It also makes zilganersen eligible for accelerated approval and priority review if relevant criteria are met.
