Ionis Pharmaceuticals is awaiting an FDA decision for zilganersen (an antisense oligonucleotide) after a pivotal Phase I–III study in Alexander disease missed secondary endpoints. The trial (NCT04849741) reported that the drug met its primary endpoint in patients aged at least 5 years, showing statistically significant stabilization in gait speed. However, Ionis reported that the therapy did not achieve the secondary goal of reducing patients’ most bothersome symptom (MBS) to a statistically significant extent. The company also stated that a substantial fraction of participants reported improvements or no changes in overall disease severity. Ionis said it does not view the secondary-endpoint miss as a likely blocker to approval given the absence of meaningful disease-modifying options in the ultra-rare condition, while highlighting that the primary endpoint reached clinical and statistical signal.