Patients Treated With REGENXBIO's MPS II Gene Therapy RGX-121 Sustain 82% Median Reduction in CSF HS D2S6 Levels Through 1 Year

According to a new data update from REGENXBIO's pivotal phase 1/2/3 CAMPSIITE clinical trial (NCT03566043) evaluating clemidsogene lanparvovec (RGX-121), an investigational adeno-associated virus (AAV) vector-based gene therapy for mucopolysaccharidosis type 2 (MPSII, also known as Hunter syndrome), 13 patients treated in the pivotal phase have shown an 82% reduction in heparan sulfate (HS) D2S6 levels in the cerebrospinal fluid (CSF) through 1 year posttreatment.¹ The company originally reported the updated data at the International Congress of Inborn Errors of Metabolism (ICIEM), held in Kyoto, Japan, from September 2 to 6, 2025, and subsequently summarized key points in a press release.

According to the press release, HS D2S6 is “a key biomarker of MPS II brain disease that is reasonably likely to predict clinical benefit.” The company also noted that the updated data is in line with earlier findings: the study previously met its primary end point for the proportion of treated patients showing CSF HS D2S6 under maximum attenuated levels at 16 weeks posttreatment (P < .0001). In addition, REGENXBIO pointed out that in the dose-finding part of the trial, an 85% decrease in CSF HS D2S6 was maintained through 2 years posttreatment for patients who received the pivotal dose. Furthermore, in the pivotal and dose-finding parts of CAMPSIITE, positive neurodevelopmental outcomes were seen, with neurodevelopmental skill acquisition or stability on all sub-scales of the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) being seen in patients treated in the pivotal portion at 1 year posttreatment. REGENXBIO states that strong correlation is seen between levels of CSF HS D2S6 at 16 weeks posttreatment and neurocognitive outcomes at 1 year posttreatment, according to new data from both the dose-finding and pivotal parts of the trial, thus supporting the utilization of CSF HS D2S6 as a surrogate end point for the accelerated approval pathway that the company is pursuing for the gene therapy product.

"These positive biomarker and functional data provide further evidence of the long-term potential of RGX-121 to change the trajectory of Hunter syndrome for boys with this devastating, degenerative disease," Steve Pakola, MD, the chief medical officer of REGENXBIO, said in a statement.¹ "The sustained reductions in CSF HS D2S6 and evidence of the strong correlation between biomarker level and neurodevelopmental improvement are highly encouraging as we look toward potential accelerated approval early next year."

With regard to safety, REGENXBIO noted that as of August 20, 2025, RGX-121 has been “well-tolerated” in the 26 patients dosed throughout CAMPSIITE. A biologics license application (BLA) for the gene therapy is currently under review by the FDA, and as of yet the agency has not raised any safety concerns during the review process.

The FDA did, however, push back the review timeline for the BLA in August 2025.² The new Prescription Drug User Fee Act (PDUFA) goal date is February 8, 2026, several months later than the original PDUFA date of November 9, 2025.

The extended timeline was instituted after the company responded to an FDA information request by submitting the longer-term clinical data from CAMPSIITE that was later presented at the ICIEM meeting. REGENXBIO also noted at the time that the FDA has conducted a prelicense inspection and bioresearch monitoring information inspection for the RGX-121 BLA. The inspection, carried out in August 2025, yielded no observations.

"Boys with this rare, devastating disease have no treatment options to address neurodevelopmental decline, and the Hunter syndrome community is in urgent need of a therapeutic option with the potential to improve these patients' lives," Curran M. Simpson, the president and chief executive officer of REGENXBIO, said in an August 2025 statement.² "We promptly provided the FDA with the information requested and expect the commercial launch plans to remain on track."