FDA Places New Clinical Hold On RGX-121 for Hunter Syndrome

The FDA has placed a new clinical hold on REGENXBIO's RGX-121 (clemidsogene lanparvovec), an investigational one-time gene therapy for Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, after asymptomatic spine MRI findings were identified in 5 participants in the CAMPSIITE study (NCT03566043).¹ REGENXBIO noted in a release that it does not expect to resubmit the RGX-121 biologics license application (BLA) in the near term.

The findings were detected through an expanded MRI monitoring plan the company implemented a few months ago following an earlier clinical hold related to a related program, RGX-111.¹ The enhanced monitoring, which included both brain and spine imaging, identified either a small nodule or a small cystic mass on spine MRIs of 5 participants who received intracisternal or intraventricular RGX-121 approximately 3 to 6 years ago. Investigators deemed the findings nonserious, and radiologists believe them likely benign; no brain nodules or masses were identified on any brain MRIs, and there is no clinical or pathological evidence confirming the nature or cause of the spine findings.

All 5 patients remain clinically stable

"Boys with neuronopathic MPS II experience a multitude of neurodevelopmental and systemic effects," Roberto Giugliani, MD, PhD, professor in the department of genetics at Universidade Federal do Rio Grande do Sul in Porto Alegre, Brazil, said in a statement.¹ Giugliani said imaging natural history is limited for this ultra-rare disease, and that asymptomatic, likely benign findings such as these may be inherent to the impact of Hunter syndrome throughout the body, adding he was pleased the affected patients are doing well and remain asymptomatic.¹

All 5 affected participants continue to do well clinically and have shown overall stability to improvement on neurocognitive and neurobehavioral assessments.¹ Because spine MRI is not normally performed for MPS II in clinical practice or trials, the underlying prevalence and clinical significance of these types of asymptomatic findings in this patient population remain unknown, and investigators plan to continue observing the affected patients with periodic imaging only.

REGENXBIO and partner NS Pharma are evaluating additional patient imaging and longer-term follow-up data, and noted they will incorporate FDA feedback, including the full clinical hold letter once received, into next steps for RGX-121.¹

"We believe these findings are unique and limited to our Hunter Syndrome program, and require longer-term follow-up and additional data analysis to assess the benefit-risk profile of RGX-121," Curran Simpson, president and CEO of REGENXBIO, said in a statement.¹ Simpson said the company remains focused on its Duchenne and retinal disease candidates, which use a different capsid and routes of administration, with near-term catalysts on track, including a planned Duchenne BLA submission this quarter and topline pivotal wet AMD data expected in the fourth quarter.¹

This marks RGX-121's second clinical hold this year

The new hold adds to a difficult regulatory year for RGX-121.² The FDA first paused testing in January after a participant receiving a similar gene therapy for a different rare condition developed brain cancer, and the agency rejected REGENXBIO's application for RGX-121 the following month, with staff reviewers finding the trial's surrogate end point unconvincing.² REGENXBIO appealed the decision and requested an urgent Type A meeting with the FDA, which led to an agreement on requirements for a potential accelerated approval pathway; the company had announced plans in June to resubmit its application before Monday's update.

RGX-121 is designed to deliver a functional copy of the IDS gene to the central nervous system in a single administration, intended to provide a permanent source of secreted iduronate-2-sulfatase (I2S) protein beyond the blood-brain barrier for long-term cross-correction of cells throughout the CNS.¹ The candidate has received orphan drug, rare pediatric disease, fast track, and regenerative medicine advanced therapy designations from the FDA, along with advanced therapy medicinal product classification from the European Medicines Agency.¹ MPS II is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme I2S, leading to accumulation of glycosaminoglycans, including heparan sulfate, that ultimately cause cell, tissue, and organ dysfunction, including in the CNS; approximately 2000 patients are diagnosed with MPS II worldwide, with more than 500 babies born with the disease each year.

Frequently Asked Questions

• What prompted the new clinical hold on RGX-121?
  The FDA placed the hold after asymptomatic spine MRI findings, either a small nodule or cystic mass, were identified in 5 participants who received RGX-121 approximately 3 to 6 years ago.
• Are the affected patients experiencing symptoms?
  No. All 5 participants remain clinically stable, with overall stability to improvement on neurocognitive and neurobehavioral assessments, and the findings were deemed nonserious and likely benign.
• How does this affect REGENXBIO's regulatory timeline for RGX-121?
  REGENXBIO said it does not expect to resubmit the RGX-121 BLA in the near term, marking the program's second clinical hold and regulatory setback in 2026.

References

1. REGENXBIO Inc. REGENXBIO Announces Regulatory Update on RGX-121 for MPS II. News release. Published August 24, 2026. Accessed August 24, 2026. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-regulatory-update-rgx-121-mps-ii
2. Alvarado D. Safety concerns spur FDA to again halt testing of Regenxbio gene therapy. BioPharma Dive. Published August 24, 2026. Accessed August 24, 2026. https://www.biopharmadive.com/news/regenxbio-fda-hunter-syndrome-hold-mri-safety/828578/