REGENXBIO Inc. announced that the US FDA issued a Complete Response Letter (CRL) on February 7, 2026 to their Biologics License Application (BLA) for RGX-121 (clemidsogene lanparvovec) for the treatment of mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome.[1] The FDA accepted the BLA under the accelerated approval pathway in May 2025.[1] The CRL cited reasons for non-approval, including uncertainty regarding study inclusion criteria to distinguish neuronopathic from attenuated disease, comparability of the external control arm to the study population, and suitability of CSF HS D2S6 as a surrogate marker likely to predict clinical benefit.[1] BLAs were supported by positive biomarker, functional outcome, and safety data from the CAMPSIITE I/II/III clinical trial up to 12 months, with RGX-121 being well tolerated in all patients.[1] REGENXBIO plans to work with the FDA on next steps, including a possible BLA resubmit with longer-term data.[1] The CRL suggests avenues such as a new study, treatment of additional patients with longer follow-up, or the use of an untreated control arm, which is challenging in an ultra-rare disease.[1]