REGENXBIO Faces Second FDA Clinical Hold on RGX-121

A second clinical hold on REGENXBIO's RGX-121 (clemidsogene lanparvovec) this year signals that intrathecally-administered gene therapies are entering a period of heightened MRI surveillance scrutiny, with direct consequences for IND holders managing CNS-targeted programs and BLA timelines across the CGT space. The FDA imposed the hold after asymptomatic spine MRI findings were identified in five participants enrolled in the CAMPSIITE study (NCT03566043), a pivotal trial evaluating the one-time gene therapy for Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome.

The findings emerged through an expanded MRI monitoring plan REGENXBIO implemented earlier this year following a prior clinical hold on the related program RGX-111. That enhanced protocol added spine imaging alongside brain MRI surveillance. In five participants who received intracisternal or intraventricular RGX-121 approximately three to six years ago, radiologists identified either a small nodule or a small cystic mass on spine MRI. Investigators classified the findings as nonserious; no brain nodules or masses were detected, and no clinical or pathological evidence has confirmed the nature or cause of the spinal findings. All five participants remain clinically stable, with overall stability to improvement on neurocognitive and neurobehavioral assessments.

For QA directors and regulatory leads overseeing CNS gene therapy INDs, the operational read is precise: expanded imaging surveillance, when applied retrospectively to long-dosed participants, can surface findings that standard clinical practice for a given indication would never have captured. Because spine MRI is not routinely performed in MPS II clinical practice or trials, the baseline prevalence and clinical significance of such asymptomatic findings in this population remain unknown. REGENXBIO and partner NS Pharma are continuing periodic imaging observation and evaluating longer-term follow-up data, pending receipt of the full clinical hold letter.

The regulatory trajectory for RGX-121 has been difficult throughout 2026. The FDA first paused the program in January following a brain cancer case in a participant receiving a related gene therapy for a separate rare condition. A Complete Response Letter followed in February, with agency reviewers finding the trial's surrogate endpoint unconvincing. REGENXBIO subsequently appealed, secured a Type A meeting, and reached agreement on an accelerated approval pathway, announcing plans in June to resubmit the BLA. The company now states it does not expect to resubmit in the near term. Separate pipeline programs in Duchenne muscular dystrophy and wet AMD, which use a different capsid and routes of administration, are reported to remain on schedule, including a planned Duchenne BLA submission this quarter.

The pace at which REGENXBIO and FDA resolve the imaging data review, and the agency's formal hold letter requirements, will determine whether an accelerated approval pathway for RGX-121 remains viable within any defined regulatory window.

Source: CGTlive via Pharma Now editorial desk, 25 August 2026.