FDA places RGX-121 on clinical hold after asymptomatic spine MRI findings in five Hunter syndrome patients. REGENXBIO delays BLA resubmission.
Written By: Rishabh Sonawane, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration has placed a clinical hold on RGX-121 (clemidsogene lanparvovec), an investigational gene therapy for neuronopathic mucopolysaccharidosis type II (MPS II), or Hunter syndrome, after expanded MRI monitoring identified asymptomatic spine abnormalities in five participants in the CAMPSIITE study.
The findings consisted of either a small nodule or small cystic mass in the spine. Investigators classified them as nonserious, and radiologists considered them likely benign. None of the five participants has developed related clinical symptoms, and all remain clinically stable or have improved on neurocognitive and neurobehavioral assessments.
No brain nodules or masses were detected on brain MRI.
RGX-121 Targets the Central Nervous System
MPS II is a rare X-linked lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase (I2S), which leads to accumulation of glycosaminoglycans, including heparan sulfate, across tissues and organs. In severe disease, accumulation within the central nervous system contributes to progressive neurodevelopmental impairment.
RGX-121 uses a one-time gene therapy approach to deliver the IDS gene to the CNS through intracisternal or intraventricular administration. The therapy is intended to enable cells within the CNS to produce I2S, including secretion of the enzyme for cross-correction of neighboring cells.
The expressed I2S protein is structurally identical to the normal human enzyme. CSF heparan sulfate, including the D2S6 disaccharide, serves as an important biomarker of disease burden and neurocognitive manifestations in MPS II.
Five Participants Had Asymptomatic Spine Findings
The abnormalities were detected through an expanded MRI surveillance program introduced several months ago following a separate clinical hold involving RGX-111. The enhanced monitoring incorporated both brain and spine imaging.
The five affected participants received RGX-121 approximately three to six years before the findings were identified. Because spine MRI is not routinely performed in MPS II clinical practice or clinical trials, the underlying prevalence and clinical significance of similar asymptomatic findings in this population remain unknown.
Investigators will continue periodic imaging of the affected participants. There is currently no clinical or pathological evidence establishing the nature or cause of the MRI findings.
Company Delays BLA Resubmission
REGENXBIO said it does not expect to resubmit the RGX-121 Biologics License Application in the near term. The company, together with partner NS Pharma, is reviewing additional patient imaging and longer-term follow-up data and plans to incorporate the FDA’s feedback, including the full clinical hold letter once received, into its development strategy.
REGENXBIO President and CEO Curran Simpson said the company believes the findings appear limited to its Hunter syndrome program and require longer-term follow-up to clarify the benefit-risk profile of RGX-121.
The company is continuing development of its Duchenne muscular dystrophy and retinal disease programs, which use different capsids and administration routes. REGENXBIO expects to submit its Duchenne BLA during the third quarter of 2026 and plans to report pivotal wet age-related macular degeneration data in the fourth quarter.
RGX-121 has received FDA Orphan Drug, Rare Pediatric Disease, Fast Track and Regenerative Medicine Advanced Therapy designations, while the European Medicines Agency has granted it advanced therapy medicinal product classification.
Reference
REGENXBIO Announces Regulatory Update on RGX-121 for MPS II | Regenxbio Inc
About the Writer
Rishabha Sonawane, BPharm (LinkedIn) is healthcare writer with a strong interest in medical writing, regulatory affairs, clinical research, and AI-driven drug discovery. He has completed specialized training from the NIH and ICMR in clinical pharmacology, clinical research, and scientific writing. Passionate about evidence-based healthcare communication, he focuses on translating complex scientific research into clear, accurate, and engaging medical content.