FDA Rejects Regenxbio’s AAV Gene Therapy RGX-121 for Hunter Syndrome

Feb. 9, 2026- The U.S. Food and Drug Administration has rejected RGX-121, an investigational AAV gene therapy developed by Regenxbio for the treatment of Hunter syndrome (MPS II), citing concerns related to clinical trial design and endpoint selection.

According to a Feb. 9 company release, the FDA questioned whether RGX-121’s clinical program adequately defined the patient population and raised issues with the use of a natural history control arm and a biomarker surrogate endpoint to support accelerated approval. RGX-121 is an AAV9-based gene therapy designed to deliver a functional copy of the iduronate 2-sulfatase (IDS) gene to the central nervous system.

The decision followed a delayed Prescription Drug User Fee Act (PDUFA) date of Feb. 8, 2026, which had been extended from an earlier Nov. 9, 2025 deadline. The FDA had accepted the one-time AAV gene therapy for accelerated approval consideration in May 2025.

Regenxbio said it provided additional clinical and biomarker data during the review process and believes these data addressed the FDA’s concerns. The company now plans to resubmit the AAV gene therapy application with longer-term follow-up data as quickly as possible.

The FDA-flagged biomarker, heparan sulfate, is widely used in AAV gene therapy development for lysosomal storage disorders and is broadly accepted by the research community as a potential surrogate endpoint. The agency previously completed pre-license and bioresearch monitoring inspections for RGX-121 without objection and did not raise safety concerns specific to the AAV9 vector used in the program.

Although RGX-121 was recently placed under a clinical hold following a brain tumor case in a patient treated with a separate Regenxbio program, the FDA confirmed that the rejection was not based on safety concerns related to RGX-121 or its AAV vector.

RGX-121 uses the same AAV9 capsid and promoter architecture employed across multiple central nervous system–targeted AAV gene therapies. AAV9 vectors have been administered to thousands of patients globally, with rare but recognized potential for genomic integration, a long-standing consideration in the AAV gene therapy field.

Hunter syndrome is an ultra-rare, progressive pediatric disease characterized by the accumulation of toxic glycosaminoglycans in the brain and peripheral tissues. Regenxbio has emphasized that early intervention with AAV-mediated gene delivery may be critical to preserving neurological function in affected children.