Gene Therapies for Mucopolysaccharidosis Show Safety, Efficacy


Interim data from trials of RGX-121 and RGX-111 were presented at WORLDSymposium 2022.

REGENXBIO’s investigational gene therapy candidates RGX-121 and RGX-111 have demonstrated interim efficacy and safety in their first in-human studies in severe mucopolysaccharidosis type 2 (MPSII) and type 1 (MPSI), respectively.1,2

The company presented interim data at the 18th Annual WORLDSymposium, February 7-11, 2022. Roberto Giugliani, MD, PhD, presented the data on RGX-121, and Raymond Wang, MD, presented the data on RGX-111.

“These data are positive... taking together these results indicate that treatment, even for patients that are already severely affected at baseline, may bring some benefits in terms of quality of life,” Giugliani said during his presentation.1

RGX-121, delivered via the intracisternal magna is being evaluated in a phase 1/2 study (NCT04571970) which has dosed 13 participants with MPSII as of December 20, 2021. Immunosuppression was discontinued in all 8 eligible participants. No treatment-related serious adverse events (AEs) have been observed as of the data cut-off date.

READ MORE: Study to Evaluate Gene-Edited Cell Therapy for MPSII

Biomarker studies revealed dose-dependent reductions in heparan sulfate (HS) in cerebrospinal fluid (CSF) in the majority of participants in all cohorts at weeks 8 and 24 along with reductions in urinary glycosaminoglycans (GAGs). Dose-dependent reductions in CSF D2S6 HS were also observed in the majority of participants at the same time points, with participants in cohort 3 approaching normal levels.Increased plasma I2S protein concentrations were observed in the majority of participants.

Investigators assessed Bayley Scale of Infant and Toddler Development (BSID-III) scores in cognition, expressive language, and fine motor skills. Participants with normal trajectory of these skills remained within normal levels and 1 participant acquired expressive language skills. Four participants demonstrated reductions in maladaptive behaviors and improvements in toileting skills via the Vineland scale (VABS-III) scores. Ten of 11 participants also showed improvements in sleep breathing following treatment.

RGX-111 is being evaluated in a phase 1/2 study (NCT03580083) that is aiming to enroll 11 participants with MPSI, 6 of which have been dosed so far. Participants are dosed in 2 cohorts of 1.0 x 1010 and 5.0 x 1010 after completing an immunosuppression regimen. The study’s primary outcome is safety, and as of December 20, 2021, no treatment-related serious AEs have been observed.

Exploratory efficacy in neurocognition was assessed viaBSID-III in the 3 younger patients while the Wechsler Abbreviated Scale of Intelligence (WASI-II) in combination with the VABSIIIwas used for the single older patient. All participants demonstrated continued skill acquisitionon their respective scales within 2 standard deviations of normative mean in measures of cognition, expressive language, and fine motor skills. The patient with the longest follow-up had higher-level scores compared with natural history at 20 months posttreatment.

The trial also assessed biomarkers such as iduronidase and HS in CSF, plasma, and urine, and found reductions from baseline and natural history in all 3 evaluable participants. Urinary total GAGs and I0S6 were also reduced from baseline in these measures.

During his presentation, Wang shared that the mother of 1 of the children in the study commented that “her child was paying closer attention to conversations, was able to ask questions indicating that they understood the situation context of the conversation, and was following along in school much better than before.”2

1. Hermatz P, Escolar M, Ficicioglu C, et al. RGX-121 gene therapy for the treatment of severe mucopolysaccharidosis type II (MPS II): Interim analysis of data from the first in-human study. Presented at: 18th Annual WORLDSymposium, February 7-11, 2022; San Diego, CA.
2. Wang R, Ficicioglu C, Giugliani R, et al. RGX-111 gene therapy for the treatment of severe mucopolysaccharidosis type I (MPS I): Interim analysis of data from the first in-human study. Presented at: 18th Annual WORLDSymposium, February 7-11, 2022; San Diego, CA.
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