REGENXBIO has provided an update on RGX-121, its investigational gene therapy for Mucopolysaccharidosis type II (MPS II), also known as Hunter Syndrome. The company said it does not expect to resubmit the Biologics License Application (BLA) for RGX-121 in the near term after the U.S. Food and Drug Administration (FDA) placed the program on clinical hold.
The FDA’s action followed the discovery of unusual but asymptomatic findings in spine MRI scans of five participants in the CAMPSIITE study. The patients had received RGX-121 through intracisternal or intraventricular administration around three to six years ago.
According to REGENXBIO, the MRI scans showed either a small nodule or a small cystic mass in the spine. Investigators have classified the findings as nonserious, while radiologists believe they are likely benign. However, there is currently no clinical or pathological evidence confirming the exact nature or cause of the findings.
Importantly, all five participants continue to do well clinically. The company said the patients remain stable or have shown improvement in neurocognitive and neurobehavioral assessments. None of the participants has developed symptoms linked to the MRI findings.
The findings were identified through an expanded MRI monitoring program introduced by REGENXBIO several months ago. The monitoring program included both brain and spine MRI scans following the clinical hold related to the company’s RGX-111 program.
No brain nodules or masses were found in the brain MRI scans.
REGENXBIO noted that spine MRI scans are not routinely performed in MPS II clinical trials or standard medical care. As a result, the company said the background rate and clinical importance of similar asymptomatic findings in people with MPS II are not known.
The affected patients will continue to be monitored through periodic imaging. REGENXBIO and its partner NS Pharma are also reviewing additional patient imaging and longer-term follow-up data.
“We believe these findings are unique and limited to our Hunter Syndrome program,” said Curran Simpson, President and CEO of REGENXBIO. He added that more long-term follow-up and data analysis are needed to better understand the benefit-risk profile of RGX-121.
The company said it will consider feedback from the FDA, including the full clinical hold letter once received, before deciding on the next steps for RGX-121.
Despite the setback to its Hunter Syndrome program, REGENXBIO said it remains focused on other gene therapy programs. These include its Duchenne muscular dystrophy and retinal disease candidates, which use a different capsid and routes of administration.
The company expects to submit its Duchenne BLA during the current quarter and plans to report topline pivotal data from its wet age-related macular degeneration (wet AMD) program in the fourth quarter.
For now, the future development timeline for RGX-121 remains uncertain as REGENXBIO and NS Pharma continue to assess the MRI findings and work with the FDA.