Regenxbio gene therapy hit with second clinical hold, halting BLA resubmission

The FDA has placed a second clinical hold on Regenxbio’s investigational gene therapy, RGX-121, for the treatment of Mucopolysaccharidosis type II (MPS II), also known as Hunter Syndrome, following the discovery of asymptomatic spine MRI findings in five participants in the CAMPSIITE study.

Given these findings, which were identified through an expanded MRI monitoring plan implemented by Regenxbio a few months ago following the clinical hold related to RGX-111, the company does not expect to resubmit the RGX-121 BLA in the near term.

In January 2026, the FDA placed two of Regenxbio's gene therapies, RGX-111 and RGX-121, on hold after a brain tumor was discovered during a routine brain scan of a child who had received RGX-111 about four years earlier. Although no tumors had been reported among the 32 patients treated with RGX-121, the agency cited similarities between the two programs. 

A few weeks later, the FDA issued a CRL for the company's BLA for RGX-121 for Hunter syndrome, citing concerns about study eligibility criteria, the comparability of the natural history external control to the study population, and the appropriateness of CSF HS D2S6 as a surrogate endpoint reasonably likely to predict clinical benefit. Regenxbio appealed the CRL, arguing it had addressed those concerns through additional data and responses to FDA information requests. The CRL had outlined several potential remedies — a new study, additional patients with longer follow-up, or an untreated control arm — but the company said each would be difficult to execute given the ultra-rare patient population.

In June, as a result of the appeal, the FDA acknowledged that the existing clinical data was sufficient to support consideration under the accelerated approval pathway and that no additional patients or studies were required. The agency asked Regenxbio to request a Type A meeting to review existing longer-term biomarker and clinical data, and to resubmit the BLA following that meeting — committing to an expedited review and labeling discussions shortly after resubmission.

Now, enhanced monitoring found either a small nodule or a small cystic mass in spine MRIs of five participants who received intracisternal or intraventricular RGX-121 approximately three to six years ago. Investigators deemed these findings to be nonserious and radiologists believe they are likely benign. Regenxbio and its partner NS Pharma are evaluating additional patient imaging and longer term follow up data, and will incorporate FDA feedback, including the full clinical hold letter once received, into next steps for RGX-121.

MPS II is a rare disease where the body can't break down sugar molecules. It is caused by a variation in the IDS gene, which contains the instructions for the production of a specific enzyme, I2S. RGX-121, an AAV therapeutic designed to deliver a functional copy of the I2S gene directly to the central nervous system, is on track to be the first gene therapy and one-time treatment for the disease.