At a Glance
- Company: REGENXBIO Inc. (Nasdaq: RGNX)
- Location: Global (US FDA review)
- Headline: Complete Response Letter (CRL) issued 7 February 2026
- Focus area: RGX-121 AAV gene therapy for mucopolysaccharidosis type II (MPS II/Hunter syndrome)
- Next steps: Request Type A meeting; plan resubmission with long-term data
What happened?
The FDA issued a Complete Response Letter (CRL) rejecting Regenxbio’s biologics license application (BLA) for RGX-121, a one-time AAV9 gene therapy for neuronopathic mucopolysaccharidosis type II (MPS II, Hunter syndrome). The CRL cited chemistry, manufacturing and controls (CMC) deficiencies, concerns over trial eligibility criteria defining neuronopathic patients, comparability of natural history controls, and heparan sulfate (HS) as a surrogate biomarker endpoint.
Why does it matter?
MPS II affects ~1 in 170,000 births, causing progressive cognitive decline with no approved neuronopathic therapy; RGX-121’s accelerated approval path relied on CSF HS normalisation as a surrogate for clinical benefit. The rejection, following a clinical hold and delayed PDUFA (originally November 2025), underscores FDA scrutiny of gene therapy vectors after a brain tumour in a related RGX-111 trial.
Who’s behind it?
REGENXBIO developed RGX-121 via AAV manufacturing platform NAV AAV9, with phase 1/2 data showing 80-95% HS reduction and cognitive stabilisation. The CRL acknowledged completed inspections but flagged development path issues.
How was it achieved?
The FDA suggested new trials, expanded cohorts with longer follow-up, or untreated controls—challenging for an ultra-rare disease. REGENXBIO believes it addressed concerns via data updates and expert input during review.
What’s next?
REGENXBIO plans a Type A meeting to discuss resubmission with extended data; clinical hold remains (stemming from RGX-111 tumour event, no causal link established).
What are people saying?
CEO Curran Simpson: “Devastating… urgent need for this irreversible ultra-rare disease.” Leerink: Rejection “unsurprising” post-hold; HS biomarker rejection “concerning” for peers like Denali/Ultragenyx.