The US Food and Drug Administration (FDA) has approved Zanvastro (zilganersen) for the treatment of pediatric and adult patients with Alexander disease.
Alexander disease is a rare leukodystrophy that impairs neuronal signalling. Most cases of Alexander disease begin before age 2 and are described as the infantile form. Signs and symptoms of the infantile form typically include an enlarged brain and head size, seizures, stiffness in the arms and/or legs, intellectual disability, and developmental delay. Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers. These deposits are found in specialized cells called astroglial cells, which support and nourish other cells in the central nervous system.
Zilganersen is an RNA-targeted therapy designed to inhibit production of excess glial fibrillary acidic protein (GFAP) that accumulates as a result of pathogenic variants in the GFAP gene. It is the first and only disease modifying therapy approved for this indication.
The approval is based on positive results from a global, multicenter, randomized, double-blind, controlled, multiple-ascending dose (MAD) phase 1-3 study (NCT04849741) that enrolled 54 participants with Alexander disease.
The study met its primary endpoint in individuals 5 years of age and older, with zilganersen 50 mg demonstrating statistically significant and clinically meaningful stabilization of gait speed as assessed by the 10-Meter Walk Test (10MWT) compared to control at week 61. Zilganersen also demonstrated improvement in gross motor function in patients 2 to 4 years of age as assessed by the Gross Motor Function Measure-88 (GMFM-88) compared to control at week 61. Additionally, secondary and exploratory endpoint results from patient/caregiver- and clinician-reported outcome assessments consistently favored zilganersen.
The treatment also demonstrated a favorable safety and tolerability profile, with most adverse events being mild or moderate in severity. Serious treatment-emergent adverse events occurred less frequently in the zilganersen group compared to control.
With this approval, Ionis Therapeutics received a Pediatric Disease and Priority Review Voucher.
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To learn more about Alexander disease and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/