FDA approves first treatment for Alexander disease, calling it a “milestone”

The US Food and Drug Administration (FDA) has approved the first treatment for Alexander disease, a rare neurologic disorder.

According to a report by Fierce Biotech on the 4th (local time), the FDA authorized Ionis Pharmaceuticals’ antisense oligonucleotide (ASO) drug Zenvastro (ingredient name zilganersen) to treat Alexander disease. It is the first time a treatment for Alexander disease has received marketing approval.

Alexander disease is a rare disorder in which mutations in the GFAP gene cause excessive production of a protein in the brain’s astrocytes. The protein aggregates to form toxic substances known as Rosenthal fibers. Zilganersen works by binding to the mRNA produced by the mutated GFAP gene, thereby preventing protein accumulation.

Dr. Emily Freilich, director of neurology at the FDA’s Center for Drug Evaluation and Research, said, “This approval is a milestone that provides the first treatment addressing the underlying cause of this disease.”

Ionis worked closely with the FDA beginning in 2021 to conduct Phase 1-3 clinical trials of zilganersen, and last fall the drug met its primary endpoint of improving mobility. The company described the approval as “the first standalone launch from our industry-leading neurology pipeline.”

Dr. Miles Minter, a biotechnology industry analyst at William Blair, called it a “breakthrough achievement,” saying, “Although this is an ultra-rare indication, for patients and families living with this devastating disease, it is an option where there was nothing before.”

Ionis plans to use the approval as a foundation to expand its rare pediatric disease pipeline. A Phase 3 trial for Angelman syndrome is currently underway, and the company is also developing treatments for Pelizaeus-Merzbacher disease, MECP2 duplication syndrome and Dravet syndrome.

Holly Kordasiewicz, Ionis’ chief development officer, said, “This approval gives hope to the other programs that follow and enables us to build the infrastructure needed to deliver them to patients quickly.”

Meanwhile, on the 1st, the day before Zenvastro’s approval, Ellis, a patient who participated in the drug’s clinical trials, celebrated her 15th birthday. Ellis’ mother, Jenny Pearson, told Fierce Biotech that when her daughter was diagnosed with Alexander disease in 2014, she was told that Ellis would “live only three more years.”

Pearson said, “The fact that my daughter is still with us and doing well is itself the greatest blessing this world could give us.”