FDA Approves First Drug for Alexander Disease, a Rare Brain Disorder
The Food and Drug Administration approved Zanvastro (zilganersen) injection on Sept. 3 for Alexander disease, a rare inherited disorder of the nervous system, and says it is the first approved treatment for the condition. The approval was granted to Ionis Pharmaceuticals and covers children and adults.
The FDA says it evaluated the drug in a multicenter, randomized, controlled study, NCT04849741, involving 49 patients aged 2 and older, plus an open-label substudy of 4 patients under 2.
In patients aged 5 and older who had measurable difficulty walking at the start, the agency says those given Zanvastro had significantly better walking speed at 61 weeks than those who received no treatment. In children aged 2 to 4, where the FDA says walking speed is not a reliable measure, a broader assessment of motor skills was used instead, and the agency says treated children improved on it while the control group declined.
For patients under 2, the FDA says direct trial data were limited by the rarity of the disease and the lack of a concurrent control group. It says pharmacokinetic modeling indicated drug levels in that age group should be similar to those in older children at the same dose.
Zanvastro is an antisense oligonucleotide, a drug designed to lower the production of a specific protein. According to the FDA, it reduces the production of abnormal glial fibrillary acidic protein, or GFAP, which builds up in the brain's supportive cells. It is injected into the spinal canal every three months by a trained health care professional.
"For patients with Alexander disease and their families, there have been no approved treatment options, only supportive care while the disease progresses," said Emily Freilich, who directs the FDA's Division of Neurology I. The agency says the disease is caused by GFAP gene mutations and affects fewer than 1 in a million people.
The FDA lists vomiting, back pain, cough, headache, and post-lumbar puncture syndrome as the most common side effects, and says aseptic meningitis has been reported in treated patients. Zanvastro carried Orphan Drug, Fast Track, Breakthrough Therapy, and Rare Pediatric Disease designations.
