Interim Trial Data Demonstrate MPS II Gene Therapy Safety and Efficacy


RGX-121 was well-tolerated across all 3 of the dose cohorts with no treatment-related serious adverse events reported.

REGENXBIO’s RGX-121, an investigational gene therapy intended for the treatment of mucopolysaccharidosis Type 2 (MPS II; Hunter syndrome), has demonstrated promising safety and efficacy in interim data from the phase 1/2/3 CAMPSIITE trial (NCT03566043).1

RGX-121 was well-tolerated across all 3 of the dose cohorts with no treatment-related serious adverse events reported as of the August 1, 2022, data cut-off. In terms of efficacy, a majority of patients in all 3 cohorts showed reductions in heparan sulfate (HS) and D2S6, glycosaminoglycans (GAGs) that are considered biomarkers of MPS II when measured in the cerebral spinal fluid (CSF). Median reductions from baseline of HS in the CSF measured at week 48 had reached 33.5% in cohort 1, 52.9% in cohort 2, and 62.5% in cohort 3. Meanwhile, median reductions from baseline of D2S6 in the CSF measured at week 48 had reached 31.9% in cohort 1, 69.4% in cohort 2, and 83.1% in cohort 3, the latter of which was noted to be approaching normal levels of D2S6.

"We are pleased to share new, positive interim data from our phase 1/2/3 CAMPSIITE trial that continues to demonstrate encouraging reductions of CSF GAGs and supports the selection of dose level 3 for our pivotal program," Steve Pakola, MD, chief medical officer, REGENXBIO, said in a statement.1 "This interim data of cohorts 1-3 demonstrate dose-dependent reductions in CSF GAGs, key biomarkers of I2S enzyme activity, in additional patients and at longer timepoints than previously presented. RGX-121 has also demonstrated positive impact on neurodevelopmental function. We believe the data supports our plan to advance RGX-121 as quickly as possible using the accelerated approval pathway with the aim of providing a much-needed new treatment option for the MPS II community."

RGX-121 is intended to deliver a functional copy of the human iduronate-2-sulfatase gene (IDS) to the central nervous system (CNS) in a single dose via REGENXBIO’s AAV9 vector, in order to restore expression of the iduronate-2-sulfatase (I2S) enzyme. The interim data included 14 patients between the ages of 5 months to 59 months at the time of dosing.2 Patients in cohort 1 received a dose of 1.3x1010 genome copies per gram (gc/g) of brain mass (n = 3), while patients in cohort 2 received a dose of 6.5x1010 gc/g of brain mass (n = 7), and those in cohort 3 received the highest dose, at 2.9x1011 gc/g of brain mass (n = 4).1 The type of mutation patients had in the IDS gene varied, with missense, gene inversion, frameshift, deletion, substitution, and splicing mutations represented.2 At the time of enrollment, 12 of the patients had been receiving weekly enzyme replacement therapy (ERT). Of these patients, 3 participants in cohort 2 discontinued ERT per investigator discretion.1,2

Neurodevelopment assessments were carried out for 8 of the participants in cohorts 1 and 2 according to the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III), specifically using the subtests for cognitive, expressive and receptive language, and fine and gross motor; though receptive language subtest data was not included in the data presented.2 Patients were separated into 2 groups based on baseline function on the cognitive subtest. Of the 4 participants who had a cognitive function above negative 2 standard deviations (SD) of the boundaries for age equivalent (AEq) score at baseline, 3 patients remained within 2 SD at the time of the last assessment of performance on the cognition, expressive language, and fine motor subtests. However, there was minimal skill acquisition among the 4 patients with cognitive function below negative 2 SD at baseline.

“RGX-121 continues to demonstrate compelling data showing its potential to impact the neurodevelopmental decline of MPS II patients, which remains an unmet need for most affected individuals," Roberto Giugliani, MD, PhD, professor, Department of Genetics, UFRGS, Medical Genetics Service, HCPA, Porto Alegre, Brazil, added to the statement.1 "A successful gene therapy with the potential to provide advantages over current standard of care is something that could provide a meaningful treatment option to the MPS II patient community. I look forward to continuing to follow this trial as the recently announced pivotal program progresses."

RGX-121 was previously granted orphan drug product, rare pediatric disease, and fast track designations by the FDA. REGENXBIO plans to submit a biologics license application supported by the interim results in 2024 via the accelerated approval pathway.

1. REGENXBIO presents additional positive interim data from the phase I/II/III CAMPSIITE trial of RGX-121 for the treatment of MPS II (Hunter syndrome) at the Society for the Study of Inborn Errors of Metabolism (SSIEM) annual symposium. News release. REGENXBIO. August 31, 2022. 
2. Giugliani, R. RGX-121 gene therapy for the treatment of severe mucopolysaccharidosis type II:CAMPSIITEphase I/II/III: A clinical study update. Poster presented at: Society for the Study of Inborn Errors of Metabolism Annual Symposium; August 31, 2022; Freiburg, Germany.
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