Ionis Pharma's Rare Disease Drugs Not Approved Therapy Meets Critical Research Targets
Patients with specific genetic disorders whose symptoms include a progressively worsening muscle control can walk faster after experimental Ionis Pharmaceuticals genetic medical treatment, a key goal of a key study. Based on these results, drugmakers say it plans to submit regulatory submissions for the first time the ultra-rare disease becomes an FDA-approved therapy.
The Ionis drug Zilganersen was developed to treat Alexander disease, a hereditary disease that causes nervous system deterioration and symptoms, including loss of functional mobility, inability to control muscles, and difficulty breathing and swallowing. As these symptoms worsen, they eventually become fatal. The current treatment for this ultra-rare disease occurs in every 1 million points estimated to be supportive care for the treatment of symptoms.
Alexander disease affects astrocytes, a type of cell that is common in the central nervous system and its function is key. The disease originates from mutations in genes that cause abnormal accumulation of glial fibrillary acidic protein (GFAP) in astrocytes. Zilganersen is an antisense oligonucleotide (ASO) designed to stop the production of excess GFAP caused by mutations in the GFAP gene.
Ionis evaluated Zilganersen in a phase 1-3 study of multiconvex doses that recruited patients with Alexander disease aged 18 months to 53 years. Participants (mainly children) were randomly assigned to receive intrathecal injections every 12 weeks of study medication or high doses of study medication or placebo. The 50 mg high-dose group was considered the key dose cohort.
The main research objective was to change gait speed from baseline to 60 weeks based on a 10-meter walk test. Ionis said on Monday that high doses of Zilganersen showed a 33% increase in gait speed, which is statistically significant and clinically significant. Secondary goals included measuring patient and physician-reported scores based on various scales to assess symptoms and disease severity. On these goals, Ionis said only that the results showed a “consistent favorable trend.”
Ionis said the study drug showed favorable safety and tolerance, adding that most adverse events were mild or moderate. The incidence of serious adverse events in the Zilganersen arm was numerically lower than that in the control group. Detailed data will be presented at the upcoming medical meeting. Ionis plans to submit a new drug application to Zilganersen in the first quarter of 2026.
Ionis specializes in ASO, a genetic medicine that uses small RNA to bind to Messenger RNA to reduce the expression of proteins that cause disease. The company's ASO study has led to the FDA-approved neuroscience drug Spinraza for spinal muscular atrophy and Qualsody for rare genetic forms of amyotrophic lateral sclerosis. Both are developed and commercialized in collaboration with Biogen.
Ionis still has partnerships, but its strategy now includes developing and commercializing drugs on its own. FDA approval of Tryngolza last year made the first wholly owned commercial asset of familial chylotype syndrome Ionis. The FDA nodded to the hereditary angioedema poison Dawnzera to Ionis last month.
William Blair analyst Myles Minter said in a Monday note sent to investors that, based on the secondary target, details of Zilganersen's results will be notified if approved. The company's peak sales for the drug were $295 million; the U.S. had about $120 million.
“Alexander disease is a superporous disease with an estimated population of less than 500 patients worldwide,” Minter said. “However, there are currently no approved therapies for Alexander disease, and given the unmet need here, we regard today's Phase 3 results as another victory for Ionis in its wholly owned neurology series, which continues to produce positive clinical results.”
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