FDA approves first drug for Alexander disease, a rare and fatal brain disorder

The FDA on Thursday approved Zanvastro (zilganersen) as the first disease-modifying treatment for Alexander disease, a rare inherited brain disorder that progressively destroys white matter in the brain and is most often fatal in childhood. Until now, families had only supportive care.

The approval covers both pediatric and adult patients. In the pivotal trial, treated patients held steady on the 10-Meter Walk Test, a standard measure of motor function, while an untreated control group lost about a third of that ability over roughly a year, a 33.3% least-squares mean difference at week 61 (p=0.0412), per Ionis investor materials. The FDA announcement calls Zanvastro the first therapy to directly target the protein buildup that drives the disease.

Serious adverse events were more common in the control arm than among treated patients, STAT News reported.

A separate finding has drawn cautious interest: in young children, treatment appeared to improve motor function rather than only stabilize it. The signal is suggestive, not proven, and the pivotal study was small, STAT notes. Long-term durability of the walking benefit beyond week 61 is not yet established.

Alexander disease is caused by mutations in the GFAP gene and affects fewer than 1,000 people in the U.S., per wire reporting. Zanvastro, developed by Ionis, is an antisense oligonucleotide, a short synthetic strand that blocks production of a disease-driving protein.

What remains unknown: the list price, payer access, and whether the early-childhood improvement signal holds up in larger or longer studies.