The US Food and Drug Administration approved zilganersen (Zanvastro) injection for pediatric and adult patients with Alexander disease, according to an agency press release.
Alexander disease is a rare, progressive neurologic condition resulting from mutations affecting the production of glial fibrillary acidic protein (GFAP). Abnormal GFAP accumulates in supportive cells in the brain and causes nervous system damage over time. The disease affects fewer than 1 in 1 million people and can cause seizures, loss of developmental milestones, difficulty walking, muscle weakness, and increased pressure in the brain.
Zilganersen is an antisense oligonucleotide that limits the production and subsequent accumulation of abnormal GFAP . Zilganersen is administered every 3 months by an injection into the spinal canal by a trained health care professional.
The FDA evaluated the efficacy and safety of zilganersen in a multicenter, randomized, controlled clinical study of 49 pediatric and adult patients with Alexander disease aged 2 years and older and an open-label substudy of 4 patients aged younger than 2 years.
At 61 weeks, patients aged 5 years and older who had measurable difficulty walking at baseline showed significantly better walking speed with zilganersen than with no treatment. Among patients aged 2 to 4 years, a broader motor assessment that included standing, walking, running, and jumping was used because walking speed was not considered a reliable measure of progress in this age group. Patients who received zilganersen improved on the motor assessment, whereas patients in the control group declined.
Clinical trial data were limited among patients aged younger than 2 years because of the rarity of the disease and the lack of a concurrent control. Pharmacokinetic modeling indicated that drug levels in this age group were expected to be similar to those in older pediatric patients receiving the same dose. Safety findings in 4 treated patients aged younger than 2 years and in older pediatric patients provided additional support for the pharmacokinetic findings. The FDA determined that the combined evidence supported inclusion of the youngest patients in the approved indication.
The most common adverse reactions are vomiting, back pain, cough, headache, and post-lumbar puncture syndrome. Aseptic meningitis has been reported in patients treated with zilganersen.
Source: US Food and Drug Administration
