Hunter syndrome gene therapy approval pathway paused again

The US Food and Drug Administration (FDA) has put a clinical hold on an experimental gene therapy for Hunter syndrome due to nodules being discovered in the spine of five patients who previously received treatment.

Biotech company Regenxbio had hoped to submit a Biologics License Application to the FDA by the third quarter of 2026 so the therapy, known as RGX-121, could be brought to market. However, it was required to pause trials earlier this year after a brain tumour was discovered in a patient who had undergone another Regenxbio gene therapy that shares certain biological and methodological features with RGX-121 (see BioNews 1340). As a result, Hunter syndrome patients previously treated with RGX-121 received spinal and brain MRIs, leading to the detection of small nodules or cystic masses in the spine of five patients who presented as asymptomatic.

'We believe these findings are unique and limited to our Hunter Syndrome programme and require longer-term follow-up and additional data analysis to assess the benefit-risk profile of RGX-121,' said Curran Simpson, the CEO and president of Regenxbio.

People with Hunter syndrome (also known as MPS II) carry a defective version of the IDS gene and are therefore unable to produce an enzyme essential for the body to function properly. They experience a range of severe life-limiting symptoms, including shortened life expectancy, with very few treatment options being available. RGX-121 aims to deliver a healthy copy of the IDS gene into brain cells using an adeno-associated virus (AAV) vector to restore enzyme production.

The AAV vector in RGX-121 shares similarities with the one used in the Regenxbio gene therapy paused due to a brain tumour being detected during a routine exam. In this instance, genetic analysis revealed that the AAV vector had integrated itself near a gene that causes tumour development when abnormally activated. The patient, who had no symptoms at the time, received surgery to remove the tumour and recovered well.

Prior to this discovery, the FDA had cleared a path for Regenxbio to reapply for the licensing of RGX-121 using an accelerated approval pathway, after having previously turned down the company's first application (see BioNews 1345).

Regenxbio plans to monitor the five RGX-121 patients by continuing brain and spinal imaging. According to the company, radiologists and investigators are considering these findings to be nonserious, and the masses to be benign. The patients' neurocognitive and behavioural assessments remain stable or show improvements. As patients with Hunter syndrome do not commonly receive spine and brain MRIs, it is difficult to assess the frequency and significance of spine findings in this population.

The company has stated that it will not pursue resubmission of its licensing application for RGX-121 in the near term.