Fast Track Designation Granted to Zilganersen, an Investigational Medicine for Alexander Disease

ION373 (zilganersen; Ionis Pharmaceuticals, Carlsbad, CA), an antisense oligonucleotide medicine, was granted Fast Track Designation by the Food and Drug Administration (FDA) for investigation as a potential treatment for people with genetically confirmed Alexander disease (AxD). According to an announcement from Ionis Pharmaceuticals earlier this month, ION373 is designed to stop excess glial fibrillary acidic protein (GFAP) production and accumulation caused by changes in the GFAP gene associated with AxD. Currently, no medications are approved by the FDA for the treatment of AxD.

Earlier in 2024, Ionis Pharmaceuticals announced that a pivotal phase 1-3 clinical study (NCT04849741) completed the enrollment of adults and children with AxD from 13 sites in 8 countries including the United States, Australia, Canada, Israel, Italy, Japan, the Netherlands, and the United Kingdom. The multi-center, double-blind, placebo-controlled, multiple-ascending dose study will evaluate the safety and efficacy of treatment with ION373 for people with AxD. During a 60-week double-blind treatment period, participants will be randomized 2:1 to receive ION373 or placebo, which will be followed by a 60-week open-label treatment period, a 120-week open-label, long-term extension period, and a 28-week post-treatment follow-up period in which all participants will receive ION373. The primary endpoint of the study is percent change from baseline in the 10-Meter Walk Test.

"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, MD, Executive Vice President and Chief Clinical Development Officer at Ionis Pharmaceuticals. "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."

AxD is an ultra-rare, progressive type of leukodystrophy occurring in approximately 1 in 1 million to 1 in 3 million people worldwide. Most cases of AxD begin in infants or young children and are caused by a mutation in the GFAP gene causing accumulation of the GFAP protein, resulting in damage to the white matter of the brain. AxD can cause symptoms including seizures, enlarged brain and head, developmental delays, and problems with movement, and ultimately causes death within 14 to 25 years after symptom onset.