FDA Places Clinical Hold on Regenexbio’s Experimental Hunter Syndrome Gene Therapy

Rare Daily Staff

The U.S. Food and Drug Administration has placed a clinical hold on Regenexbio’s experimental gene therapy for Hunter syndrome after doctors identified small, asymptomatic abnormalities on spinal MRI scans in five study participants, the company said Monday.

Shares of Regenexbio fell nearly 25 percent in early trading following the news.

Regenexbio said it does not expect to resubmit its application for approval of the treatment, RGX-121, in the near term as it gathers more data and discusses the findings with regulators.

The therapy is being studied as a one-time treatment for mucopolysaccharidosis type II, or MPS II, a rare inherited lysosomal storage disorder also known as Hunter syndrome. The condition primarily affects boys and can cause progressive damage throughout the body, including the brain and nervous system.

RGX-121 is designed to deliver a functional copy of the gene that produces iduronate-2-sulfatase, an enzyme that is missing or deficient in people with Hunter syndrome. The goal is to enable cells in the central nervous system to produce the enzyme over the long term, potentially addressing disease effects that conventional treatments may struggle to reach beyond the blood-brain barrier.

The MRI findings involved either a small nodule or a small cyst-like mass in the spine. The five participants had received RGX-121 via delivery into fluid-filled spaces around the brain or directly into the brain approximately three to six years earlier.

Regenexbio said the participants have not shown symptoms related to the MRI findings and are doing well clinically. Investigators considered the findings nonserious, while radiologists believe they are likely benign, according to the company. No comparable nodules or masses were found on brain scans.

Still, the cause and clinical significance of the spinal findings remain unclear. Spine MRIs are not routinely used in Hunter syndrome care or clinical trials, Regenexbio said, leaving researchers without a clear baseline for how commonly such abnormalities may occur in people with the disease.

The company expanded its MRI monitoring program several months ago after a separate clinical hold involving RGX-111, an experimental treatment for MPS I. The expanded plan included brain and spinal imaging and led to the detection of the five cases.

“We believe these findings are unique and limited to our Hunter syndrome program,” Regenexbio CEO Curran Simpson said, adding that the company needs longer-term follow-up and further analysis to assess the therapy’s benefits and risks.

Regenexbio and its partner, NS Pharma, said they will review additional patient imaging, longer-term follow-up data, and FDA feedback before determining next steps for RGX-121.

“Boys with neuronopathic MPS II experience a multitude of neurodevelopmental and systemic effects,” said Roberto Giugliani, a medical genetics professor in Brazil and an investigator cited by the company. “While imaging natural history is limited for this ultra-rare disease, I believe that asymptomatic, likely benign findings like these may be inherent to the impact of Hunter Syndrome throughout the body.”

Photo: Regenexbio CEO Curran Simpson