REGENXBIO Presents Additional Positive Interim Data from Phase I/II Trial of RGX-121 for the Treatment of MPS II (Hunter Syndrome) at 17th Annual WORLDSymposium™ 2021
- RGX-121, a one-time gene therapy for MPS II, continues to be well-tolerated with no drug-related serious adverse events
- Biomarkers and measures of neurodevelopmental function from patients in Cohort 1 and 2 indicate CNS activity following RGX-121 administration
- Consistent reductions in CSF levels of biomarkers up to 2 years after RGX-121 administration
- Continued cognitive development and skill acquisition observed
- Evidence of systemic enzyme expression and biomarker activity
- Increased plasma enzyme levels
- Rapid urine biomarker reductions observed in ERT-naïve patients; reduced liver and spleen volumes in one ERT-naïve patient
- REGENXBIO plans to initiate dosing of patients in Cohort 3 in the first quarter of 2021
"We are pleased to report additional positive data from Cohorts 1 and 2 of our ongoing Phase I/II trial of RGX-121. Data from the eight patients dosed to date continue to show an encouraging safety profile of RGX-121, and highlight the potential of RGX-121 to restore biological enzyme activity and improve outcomes for MPS II patients," said
"The consistent biomarker data and neurocognitive development updates from patients in the RGX-121 trial are compelling, especially the data from patients who were not treated with enzyme replacement therapy prior to enrolling in the trial," said Dr. Roberto Giugliani, Professor,
RGX-121 is an investigational one-time gene therapy designed to deliver the gene that encodes the iduronate-2-sulfatase (I2S) enzyme using the AAV9 vector. RGX-121 is administered directly to the central nervous system (CNS). Patients in Cohorts 1 and 2 received doses of RGX-121 at 1.3x1010 genome copies per gram (GC/g) of brain mass and 6.5x1010 GC/g of brain mass, respectively.
The study findings that will be presented at the WORLDSymposium are available under the Presentations & Publications page in the Media section of the company's website located at www.regenxbio.com.
Data Summary and Safety Update
CSF Biomarker Data
Biomarker data from patients in both cohorts indicate encouraging signals of I2S enzyme activity in the CNS following one-time administration of RGX-121. Heparan sulfate (HS) and D2S6, a component of HS, are glycosaminoglycans (GAGs) that are key biomarkers of I2S enzyme activity and are being measured in the cerebrospinal fluid (CSF) at baseline and after administration of RGX-121. Elevated levels of HS and D2S6 correlate closely with the neuronopathic phenotype of MPS II. HS levels in the first six patients in Cohorts 1 and 2 demonstrated consistent reductions in the CSF up to 2 years following RGX-121 administration, with median reductions from baseline of 30.3% at Week 8 and 35.8% at the last timepoint available for each patient. Similarly, these patients demonstrated consistent reductions of D2S6 up to 2 years following RGX-121 administration, with median reductions from baseline of 44.2% at Week 8 and 39.2% at the last timepoint available for each patient. In addition, I2S enzyme concentration in the CSF, which was undetectable in all patients prior to dosing, was measurable in patients from Cohort 2 after RGX-121 administration.
Neurocognitive Development Data
Patients in Cohorts 1 and 2 also demonstrated continued neurocognitive development up to two years after RGX-121 administration. Five patients in Cohorts 1 and 2 have reached at least 6 months of follow-up since RGX-121 administration, and of those five patients, three continued to demonstrate neurocognitive development within a normal range, according to the Bayley Scales1. Two patients entered the study with significant delay in neurocognitive development at baseline. After RGX-121 administration, one of these patients demonstrated ongoing neurocognitive development, and both patients continued to acquire expressive and receptive language skills based on the Bayley Scales.
Systemic Biomarker Data and Clinical Efficacy
Patients in Cohorts 1 and 2 demonstrated evidence of I2S enzyme activity in plasma and urine following administration of RGX-121. Five of six patients demonstrated increases in I2S enzyme concentration levels in plasma over time. Six of eight patients dosed with RGX-121 were receiving ERT at the time of enrollment in the study. All six of these patients have shown decreased total GAG levels in urine up to two years following RGX-121 administration. Notably, two patients in Cohort 2 who were naïve to ERT demonstrated rapid reductions in urine total GAG levels following RGX-121 administration; one of these patients with 24 weeks of follow-up showed significant reductions in liver and spleen volumes.
RGX-121 is a product candidate for the treatment of Mucopolysaccharidosis Type II (MPS II), also known as Hunter Syndrome. RGX-121 is designed to use the AAV9 vector to deliver the human iduronate-2-sulfatase gene (IDS) which encodes the iduronate-2-sulfatase (I2S) enzyme to the central nervous system (CNS). Delivery of the IDS gene within cells in the CNS could provide a permanent source of secreted I2S beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS. RGX-121 has received orphan drug product, rare pediatric disease and Fast Track designations from the
About Mucopolysaccharidosis Type II (MPS II)
MPS II, or Hunter Syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (I2S) leading to an accumulation of glycosaminoglycans (GAG), including heparan sulfate (HS) in tissues which ultimately results in cell, tissue, and organ dysfunction. In severe forms of the disease, early developmental milestones may be met, but developmental delay is readily apparent by 18 to 24 months. Specific treatment to address the neurological manifestations of MPS II and prevent or stabilize cognitive decline remains a significant unmet medical need. Key biomarkers of I2S enzymatic activity in MPS II patients include its substrate heparan sulfate (HS), which has been shown to correlate with neurocognitive manifestations of the disorder.
About REGENXBIO Inc.
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1 Bayley Scales of Infant and
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