The FDA has approved Ionis Pharmaceuticals’ ZANVASTRO, or zilganersen, for pediatric and adult patients with Alexander disease, making it the first approved therapy intended to modify the underlying disease process.
Alexander disease is an ultra-rare, progressive neurological disorder that affects about one in 1 million to one in 3 million people worldwide. It is caused by disease-causing changes in the GFAP gene that result in excess accumulation of glial fibrillary acidic protein, or GFAP, in astrocytes. The resulting dysfunction can damage neurons and myelin and lead to worsening motor, cognitive, autonomic and gastrointestinal problems.
Until now, care for Alexander disease has focused mainly on symptom management. The condition can begin during infancy, childhood or adulthood and may lead to loss of mobility and independence, difficulty swallowing and protecting the airway, and death within 14 to 25 years after symptoms begin.
ZANVASTRO is an RNA-targeted therapy designed to reduce production of GFAP. The 50-milligram dose is administered through an intrathecal injection once every three months.
The FDA’s decision was based on a global Phase 1-3 study involving 54 people with Alexander disease, ages 1.5 to 53, at 13 sites in eight countries. Participants were randomly assigned in a two-to-one ratio to receive ZANVASTRO or control during a 60-week double-blind treatment period.
Among participants age 5 and older, the pivotal 50-milligram dose achieved the primary endpoint of improved stabilization of gait speed on the 10-Meter Walk Test at Week 61. The least-squares mean difference versus control was 33.3%, with a p-value of 0.041. Children ages 2 through 4 showed improved gross motor function on the Gross Motor Function Measure-88 compared with control.
Most adverse events were mild or moderate, Ionis said. The most common adverse reactions were vomiting, back pain, cough, headache and post-lumbar-puncture syndrome. The treatment carries a warning for aseptic meningitis.
The approval also awarded Ionis a Rare Pediatric Disease Priority Review Voucher. ZANVASTRO is expected to be available in the United States in coming weeks. Ionis has licensed rights outside the U.S. to Recordati, which expects regulatory submissions in Europe and Japan in 2027
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