Additional Positive Interim Data from Phase I/II/III CAMPSIITE™ Trial of REGENXBIO's RGX-121 for the Treatment of MPS II (Hunter Syndrome) Presented at 19th Annual WORLDSymposiumTM
- RGX-121, a potential one-time gene therapy for the treatment of MPS II, continues to be well-tolerated with no drug-related SAEs across three dose levels
- Additional data from patients in Cohort 3 using pivotal program dose level continue to demonstrate largest reductions in CSF GAGs, continuing to approach normal levels at 48 weeks
- New, longer-term clinical measures demonstrated continued improvement in neurodevelopmental and daily activity skill acquisition up to three years after RGX-121 administration
- Positive interim data continues to support plan to file Biologics License Application in 2024 using the accelerated approval pathway
"These new results demonstrate sustained reductions in CSF GAGs and an encouraging, long-term clinical profile of RGX-121 up to three years," said
"Treatment options to address the neurological manifestations of MPS II remain a significant unmet medical need for patients," said Can Ficicioglu, M.D., Ph.D., Professor of Pediatrics at the
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. Data presented were from the Phase I/II portion of the CAMPSIITE trial in which the primary endpoint is to evaluate the safety of RGX-121. Secondary and exploratory endpoints include cerebral spinal fluid (CSF) glycosaminoglycans (GAGs), neurodevelopmental assessments, caregiver reported outcomes and systemic biomarkers. RGX-121 is administered directly to the central nervous system (CNS). As of
Data Summary and Safety Update
CSF GAGs Data
Biomarker data from patients in all three cohorts indicate encouraging, dose-dependent reductions of CSF GAGs following one-time administration of RGX-121. Heparan sulfate (HS) and D2S6, a component of HS closely correlated with severe MPS II, are GAGs that are key biomarkers of I2S enzyme activity and are being measured in the CSF at baseline and after administration of RGX-121. CSF GAGs have the potential to be considered a surrogate endpoint that is reasonably likely to predict clinical benefit in MPS II disease under the accelerated approval pathway, as buildup of GAGs in the CSF of MPS II patients correlates with clinical manifestations including neurodevelopmental deficits.
The majority of patients in all cohorts demonstrated reductions of CSF HS from baseline at the last time point available with dose-dependent reductions seen at Weeks 8, 24, and 48 post RGX-121 administration. At Week 48, median reduction of CSF HS from baseline was 33.5% in Cohort 1, 48.9% in Cohort 2 and 64.7% in Cohort 3.
Similarly, dose-dependent reductions of CSF HS D2S6 from baseline were observed at last time point available in the majority of patients, with Cohort 3 patients approaching normal levels at 48 weeks. All three cohorts demonstrated a reduction in HS D2S6 with dose-dependent reductions seen at Weeks 8, 24, and 48. Median reductions from baseline of 31.9% in Cohort 1, 71.9% in Cohort 2 and 83.3% in Cohort 3 were seen at Week 48.
In addition, I2S protein concentration in the CSF, which was undetectable in all patients prior to dosing, was measurable in 10 of 11 Cohort 2 and 3 patients after RGX-121 administration.
Neurodevelopmental and Systemic Data
Improvements in neurodevelopmental function and caregiver reported outcomes demonstrated CNS activity on two developmental scales up to three years after RGX-121 administration. As measured by the Bayley Scales of Infant and
Additionally, evidence of systemic enzyme expression and biomarker activity was observed in all cohorts following RGX-121 administration. The majority of patients demonstrated increases in I2S protein concentration levels in plasma following administration of RGX-121. Total urine GAG measures demonstrated evidence of a systemic effect of RGX-121, independent of ERT treatment.
The study findings presented at the 2023 WORLDSymposium will be available under the Presentations & Publications page in the Media section of
About the CAMPSIITE™ Trial
CAMPSIITE is a Phase I/II/III multicenter, open-label trial enrolling boys with MPS II, aged four months up to five years of age. As part of a pivotal program expansion, CAMPSIITE is expected to enroll up to 10 MPS II patients to support the BLA filing using the accelerated approval pathway, with the potential to enroll additional patients. These patients will receive a dose of 2.9x1011 GC/g of brain mass of RGX-121, which is the same dose being evaluated in Cohort 3 of the Phase I/II trial. The pivotal program is using commercial-scale cGMP material from
CAMPSIITE is a global trial, which is expected to include sites in
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 (GAGs), including heparan sulfate (HS) in tissues which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system (CNS). MPS II is estimated to occur in 1 in 100,000 to 170,000 births. 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 remains a significant unmet medical need. Key biomarkers of I2S enzymatic activity in MPS II patients include its substrate heparan sulfate (HS) D2S6, which has been shown to correlate with neurocognitive manifestations of the disorder.
About REGENXBIO Inc.
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