As reported on Drugs.com, REGENXBIO has announced that the U.S. Food and Drug Administration (FDA) has halted clinical testing of its investigational gene therapies RGX‑111 and RGX‑121, two programs targeting the ultra‑rare lysosomal storage disorders MPS I (Hurler syndrome) and MPS II (Hunter syndrome).
Reason for the Clinical Hold
The agency’s action follows early findings from a single pediatric patient enrolled in the Phase I/II RGX‑111 study. The child, who is asymptomatic, was found during routine imaging to have developed an intraventricular central nervous system tumor approximately four years after receiving intracisternal administration of RGX‑111.
Initial genetic analysis of the tumor revealed evidence of AAV vector genome integration and increased activity of PLAG1, a proto‑oncogene known to be involved in chromosomal rearrangements. Investigators and regulators have not yet determined whether the tumor is related to treatment, and the company emphasized that causality remains unconfirmed.
No similar safety events have been identified in the other nine participants treated with RGX‑111, nor among the 32 individuals who have received RGX‑121.
FDA Extends Hold to RGX‑121
Although the incident occurred in an RGX‑111 recipient, the FDA extended the hold to RGX‑121, citing shared characteristics between the two gene therapy candidates, including similar delivery approaches and overlapping patient populations.
REGENXBIO’s president and CEO Curran Simpson expressed disappointment with the broader suspension, stating that RGX‑121 has demonstrated a favorable safety record over nearly seven years of follow‑up in its clinical program. He noted concerns that delays could worsen neurological decline in boys living with MPS II, a condition with few treatment options.
The company is still awaiting the FDA’s formal clinical hold letter with additional details.
About RGX‑121
RGX‑121 (clemidsogene lanparvovec) is designed as a one‑time CNS‑directed gene therapy intended to provide long‑term delivery of the iduronate‑2‑sulfatase (IDS) enzyme, which is deficient in individuals with MPS II. By enabling cells within the central nervous system to produce IDS, the therapy aims to establish sustained enzyme activity beyond the blood‑brain barrier.
The candidate has received multiple FDA designations—including Orphan Drug, Rare Pediatric Disease, Fast Track, and RMAT—as well as ATMP classification from the European Medicines Agency.
