FDA Reconsiders Regenxbio Hunter Syndrome Gene Therapy After Four-Month Rejection

Regenxbio disclosed the FDA’s decision on 22 June 2026 to accept a resubmission for NAVSUNLI, an AAV9 vector delivering iduronate-2-sulfatase to the CNS. The therapy targets the neuronopathic form of Hunter syndrome, where intravenous enzyme replacement fails to cross the blood-brain barrier and cognitive decline continues. The agency cited no new clinical data but referenced internal policy adjustments following leadership changes at the agency.

This reversal occurs against a backdrop of three prior FDA rejections of CNS-directed gene therapies since January 2026, including UniQure’s Huntington’s program. Families with MPS II face a median survival of 12–15 years in the severe form; any delay directly affects access to potentially disease-modifying treatment. The pattern suggests that surrogate biomarker thresholds and manufacturing requirements are being re-evaluated under political pressure rather than new evidence.

Observational natural-history cohorts show that even modest reductions in CSF glycosaminoglycans correlate with stabilized developmental quotients, yet no phase 3 trial has yet demonstrated a statistically significant cognitive endpoint. Regulatory whiplash risks eroding sponsor willingness to pursue ultra-rare CNS indications where trial sizes are inherently small.

Next steps include a 60-day resubmission window and an expected advisory committee meeting by October. Sponsors of similar AAV programs are now recalibrating CMC packages and biomarker strategies in anticipation of shifting FDA expectations.