FDA approves Ionis’ zilganersen as Zanvastro for Alexander disease

The U.S. Food and Drug Administration has granted approval to zilganersen, an antisense oligonucleotide developed by Ionis Pharmaceuticals, for the treatment of Alexander disease. The drug will be sold under the brand name Zanvastro and is the first-ever medicine approved for this ultra-rare genetic disorder.

Alexander disease is caused by mutations in the GFAP gene, leading to toxic protein buildup in astrocytes that damages the brain and nervous system. Prior to this approval, no disease-modifying therapies existed, and patients faced a poor prognosis, often with life expectancy limited to early childhood.

The approval follows results from a Phase 1-3 clinical trial of zilganersen, which Ionis launched in 2021 in close collaboration with the FDA. The trial used the first natural history study of Alexander disease-as a control arm, a study that Elise Pearson’s mother, Jenny Pearson, had helped initiate.

In the trial, zilganersen-treated patients, the trial met its primary endpoint of improved mobility last fall. Pearson reported that her daughter Elise, who began experiencing seizures at 16 months and was diagnosed with Alexander disease in 2014, has shown meaningful clinical improvement since starting the drug.

“Zilganersen stopped Elise’s disease in its tracks,” Pearson said. “The fog’s being lifted on her brain, and her personality gets a chance to come out more and more.” Elise celebrated her 15th birthday on September 1, just days before the FDA’s approval decision.

While not a cure, zilganersen works by binding to the mutant GFAP mRNA, reducing the production of the harmful protein that forms Rosenthal fibers in astrocytes. Ionis’ chief development officer, Holly Kordasiewicz, Ph.D., described the preclinical data as “phenomenal,” noting reversal of underlying pathology in animal models and clear pharmacodynamic biomarkers.

Emily Freilich, M.D., director of the Division of Neurology in the FDA’s Center for Drug Evaluation and Research, called the approval a “landmark moment” for the Alexander disease community, emphasizing that it addresses the underlying cause of a serious and rare condition.

Myles Minter, Ph.D., a biotech industry analyst with William Blair, had previously told Fierce that the approval was “overwhelmingly likely” and called it a “breakthrough” for families with no prior treatment options.

For Ionis, the approval marks its first independent launch from its neurology pipeline. CEO Brett Monia, Ph.D., stated that Zanvastro represents a milestone in the company’s strategy to build a rare disease franchise.

Kordasiewicz said the approval is “just the tip of the iceberg,” citing ongoing Phase 3 development for Angelman syndrome and other programs in Pelizaeus-Merzbacher disease, MECP2 duplication syndrome, and Dravet syndrome. She added that the infrastructure built for Zanvastro will help accelerate future rare disease programs.

The company is also expanding into larger indications, including cardiology, where it launched its first solo drug, Tryngolza, in 2024, and is pursuing Lp(a)-lowering therapies in collaboration with Novartis. Minter suggested that success in these areas could position Ionis to develop next-generation therapies independently.

Long-term, Minter sees potential for Ionis to evolve beyond its reputation as an R&D powerhouse, citing growing royalty streams and collaborative revenue exceeding half a billion dollars annually. He noted that while the company’s early partnerships with Biogen on drugs like Spinraza were strategic, some investors may now view those deals as limiting Ionis’ full commercial potential.

As of the approval, Elise Pearson continues to show stability and developmental progress, her mother saying that each day with her is a blessing, despite ongoing challenges.