REGENXBIO’s Hunter Syndrome Gene Therapy Fails To Win FDA Nod

 

The FDA recommended that REGENXBIO run a new study, treat more patients and include a placebo arm to support a resubmission for the gene therapy RGX-121.

After waiting through a three-month delay, REGENXBIO’s investigational gene therapy RGX-121 has been rejected by the FDA for the treatment of Hunter syndrome, an ultra-rare neurodegenerative condition.

In a complete response letter (CRL), the regulator cited “uncertainty” over the eligibility criteria that REGENXBIO used for the study included in RGX-121’s data package. The agency also questioned the applicability of using natural history external controls and the validity of the surrogate endpoint—cerebrospinal fluid levels of the biomarker DS26—as basis for approval.

For a resubmission, the FDA recommended running a new study, adding more patients, following them for longer periods and using an untreated comparator group. REGENXBIO, however, called these options “challenging” in a Monday release, given the ultra-rare nature of Hunter syndrome. RGX-121 had been accepted into the FDA’s accelerated approval program in May 2025.

“The CRL indicates the FDA is clearly being cautious on granting accelerated approvals without placebo-controlled data,” William Blair told investors in a Monday note. In turn, this could pose a regulatory risk for Denali Therapeutics, which is also awaiting the agency’s verdict on the Hunter syndrome therapy tividenofusp alfa, for which a target action date has been set for April 5. While Denali did not rely on natural history comparators to establish the efficacy of its therapy, the study also did not have a placebo arm.

Regenxbio is trading at $9.05 before the opening bell on Tuesday, down 12% from its previous closing price of $10.31.

The FDA had previously agreed to REGENXBIO’s protocol, the biotech said on Monday, adding that throughout the application process, the biotech had “addressed the points raised in the CRL” by submitting additional data and complying with the regulator’s information requests.

CEO Curran Simpson called the rejection “devastating for the families of boys living with” Hunter syndrome. The biotech will seek a Type A meeting with the FDA to discuss not just the path forward for RGX-121 but also to “provide additional evidence” from experts to support the effectiveness of the gene therapy.

To support the approval application for RGX-121, REGENXBIO filed data from the Phase 1/2/3 CAMPSIITE study, which in February 2024 demonstrated that at 16 weeks, the gene therapy elicited 86% decrease in DS26, a key disease biomarker, in the cerebrospinal fluid of treated patients. CAMPSIITE enrolled 48 boys aged 4 months to 5 years of age with Hunter syndrome.

At the time of the readout, 80% of patients treated with the pivotal dose of RGX-121 were able to discontinue or stay naïve of enzyme replacement therapy.

Hunter syndrome affects around 500 boys in the U.S. The disease is caused by mutations to the iduronate-2-sulfatase (IDS) gene, rendering its corresponding enzyme defective and leading to a toxic buildup of waste inside cells across the body. REGENXBIO’s RGX-121 counters this mechanism by delivering a functioning copy of the IDS gene.

https://www.biospace.com/fda/regenxbios-hunter-syndrome-gene-therapy-fails-to-win-fda-nod