FDA accepted Ionis’ filing for zilganersen for priority review last month, setting a September 22 deadline for what would be the first cleared treatment for Alexander disease.
AxD affects roughly 300 people in the U.S., a population so small the drug’s pivotal trial ran Phase 1-3 combined. The study showed a 33.3% increase in gait speed over placebo in the 10-meter walk test at week 61, with stabilization in the zilganersen cohort against declining performance in the control arm. Researchers presented updated data at the American Academy of Neurology annual meeting Tuesday, showing “statistically and clinically meaningful stabilization of motor function” across key secondary endpoints.
Zilganersen missed one secondary endpoint: the most bothersome symptom. 42.1% of patients improved on zilganersen versus 56.3% who worsened on placebo, but the result didn’t reach statistical significance. William Blair analysts said the MBS miss likely drove the nominal statistical significance in the Patient Global Impression of Change score, yet they’re still confident FDA will clear the drug by September 22, citing high unmet need and regulatory flexibility on which secondary endpoint the agency anchors to.
Peak sales forecasts split: William Blair sees $295 million, while Ionis expects more than $100 million. Ionis will partner the drug outside the U.S., and the commercial infrastructure it builds here could set up its next neurology launch — obudanersen for Angelman syndrome, Phase 3 data expected in 2026, launch targeted for 2028 in a disease affecting more than 100,000 people in major geographies.
September 22 is the hard deadline.
— Sarah Chen