REGENXBIO has reported that the US Food and Drug Administration (FDA) has placed a clinical hold on its investigational gene therapy, RGX-121 (clemidsogene lanparvovec), developed for the treatment of mucopolysaccharidosis type II (MPS II).
Also known as Hunter syndrome, MPS II is a rare disease caused by a deficiency in the enzyme I2S, resulting in the build-up of glycosaminoglycans in tissues, leading to a range of symptoms and progressive organ dysfunction.
The update follows the detection of asymptomatic findings in the spine magnetic resonance imaging (MRIs) of five participants enrolled in the CAMPSIITE study of RGX-121.
As a result, the company does not anticipate resubmitting its biologics licence application (BLA) for RGX-121 in the near future.
Regenxbio stated that the findings were discovered through an expanded MRI surveillance protocol introduced a few months ago.
This enhanced imaging, which included both brain and spine scans, was implemented after a separate clinical hold was instituted regarding RGX-111.
As part of this protocol, spine MRIs in five subjects who had received intracisternal or intraventricular RGX-121 nearly three to six years earlier identified the presence of either a small nodule or a cystic mass.
These patients continued to show overall stability or improvement in neurocognitive and neurobehavioural assessments and remained clinically unaffected by the findings.
The company stated that investigators classified these MRI observations as nonserious and reported that radiologists believed them to be likely benign. No abnormalities were found on the brain MRIs.
Regenxbio president and CEO Curran Simpson said: “We believe these findings are unique and limited to our Hunter Syndrome programme, and require longer-term follow-up and additional data analysis to assess the benefit-risk profile of RGX-121.
“We remain focused on our Duchenne and retinal disease candidates, which utilise a different capsid and routes of administration, with near-term catalysts that are on track, including the planned submission of the Duchenne BLA this quarter and the wet AMD topline pivotal data announcement in the fourth quarter.”
The frequency and significance of asymptomatic spine findings in individuals with MPS II are unknown, as spine MRI is not routinely performed in this context.
Regenxbio indicated that monitoring of affected trial participants will continue through periodic imaging only.
Along with its partner NS Pharma, the company is reviewing further patient imaging and longer-term data and will determine next steps for RGX-121 following receipt of the FDA’s full clinical hold letter.
RGX-121 is a one-time gene therapy designed to deliver the iduronate-2-sulfatase (IDS) gene directly to the central nervous system.
In October 2025, Regenxbio concluded enrolment of subjects in the AFFINITY DUCHENNE clinical study evaluating its RGX-202 gene therapy candidate for Duchenne muscular dystrophy.
