The FDA placed a clinical hold on the RGX-121 gene therapy for MPS II after spinal MRI scans showed unexpected abnormalities in five study participants.
Regulatory action follows imaging findings
Investigators in the CAMPSIITE trial (NCT03566043) identified either a small nodule or a cystic mass in the spines of patients who received the investigational product by intracisternal or intraventricular injection three to six years earlier. The lesions were classified as non‑serious, and reviewing radiologists judged them likely benign. All five individuals remained asymptomatic and continued to show stable or improving neurocognitive scores.
Because spinal MRI is not a routine part of standard care for Hunter syndrome, the prevalence of similar silent findings in the broader patient community is unknown. The company, REGENXBIO, noted that no clinical or pathological evidence links the therapy to the lesions, and no nodules were seen on brain scans.
In response, the sponsor will keep the affected participants under periodic imaging surveillance rather than intervene surgically. The agency’s full clinical hold letter will shape the next steps, and the firm said it does not plan to resubmit a biologics license application in the near term.
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Company outlook and ongoing programs
CEO Curran Simpson said the findings appear unique to the Hunter syndrome program and require longer‑term follow‑up to reassess the benefit‑risk balance. He added that the company remains focused on its Duchenne muscular dystrophy and retinal disease candidates, which use a different capsid and delivery route. Those programs have near‑term milestones, including a planned submission for the Duchenne therapy this quarter and anticipated wet‑AMD data later in the year.
The therapy was designed as a one‑time delivery of a functional IDS gene to central nervous system cells, aiming to produce iduronate‑2‑sulfatase that can cross the blood‑brain barrier and correct surrounding cells. The expressed enzyme matches the natural human protein, according to the sponsor.
While the current hold stalls progress for this particular indication, the broader gene‑therapy field has seen similar pauses. When a vector‑related safety signal emerges, regulators typically require additional imaging or biomarker data before allowing trials to continue. The situation mirrors earlier actions taken after a separate hold on the company’s MPS I candidate, RGX‑111, which prompted an expanded imaging protocol that ultimately uncovered the spinal findings in the present study.
Clinical context of Hunter syndrome
MPS II is an X‑linked lysosomal storage disorder caused by deficiency of iduronate‑2‑sulfatase. Accumulation of glycosaminoglycans leads to progressive organ damage, often involving the brain. In severe cases, developmental delay becomes evident by 18 to 24 months, showing the need for treatments that address neurological involvement.
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Roberto Giugliani, a professor of genetics in Brazil, remarked that asymptomatic, likely benign imaging findings may be part of the disease’s systemic impact. He expressed relief that the patients remain symptom‑free.
Regulatory designations previously granted to the therapy include orphan drug, rare pediatric disease, fast track, and regenerative medicine advanced therapy status from the FDA, as well as an advanced therapy medicinal product label from the European Medicines Agency.
Future decisions will depend on the FDA’s feedback and on additional imaging data collected by REGENXBIO and its partner NS Pharma. Until the agency lifts the hold, the investigational product will not move forward in the current trial.