REGENXBIO Announces Interim Data from Phase I/II Trial of RGX-121 for the Treatment of Mucopolysaccharidosis Type II (MPS II)
"Patients with MPS II continue to have significant difficulties despite the availability of systemic enzyme replacement therapy which doesn't address manifestations of the disease in the central nervous system such as impaired cognitive development. We are pleased with the emerging safety profile in the first patients dosed with RGX-121 via single intracisternal administration. We are also encouraged by the positive results from this cohort, including a meaningful and sustained reduction in heparan sulfate suggesting that the gene therapy can potentially restore intracellular activity of the I2S enzyme, as well as the early signs of neurocognitive stability that have been observed," said
In Cohort 1 of the Phase I/II study, three patients were dosed intracisternally at the ages of 5 months (Patient 1), 35 months (Patient 2), and 7 months (Patient 3) with 1.3x1010 genome copies per gram (GC/g) of brain mass. Safety follow-up post-administration of RGX-121 ranges from 12 weeks to 68 weeks. As of
Heparan sulfate (HS) is a key biomarker of I2S enzyme activity and is being measured in the cerebral spinal fluid (CSF) following administration of RGX-121. In MPS II patients, high amounts of HS accumulate in the CNS, closely correlating with neurocognitive decline. In the CSF of all three patients enrolled in Cohort 1, HS levels demonstrated a mean reduction of 33.3% from baseline to Week 8. Patient 1 demonstrated consistent decreases in HS levels in the CSF over time, with a 27.4% reduction from baseline at Week 8 and a 43.6% reduction from baseline at Week 48, the latest timepoint available. Patient 2 also demonstrated a decrease of HS levels in the CSF, with a 30.9% reduction from baseline to Week 8, the latest timepoint available. Patient 3 demonstrated a decrease in HS levels in the CSF with a reduction of 41.6% from baseline to Week 8, the latest timepoint available.
In addition, for the two patients who have progressed beyond Week 24, preliminary data indicates stability of neurocognitive development. Patient 1 has continued to exhibit normal cognitive development as expected at Week 48, the time of last assessment. Patient 2 was diagnosed with a neurocognitive decline prior to dosing with RGX-121 and remains developmentally delayed, but preliminary assessments suggest stable neurocognitive development since dosing.
"It is encouraging to see a reduction in heparan sulfate in the CSF as it is a strong marker of the decline in neurocognitive development experienced by patients with MPS II, and closely correlates with the severity of the disease. The potential to provide therapeutic benefit directly to the CNS would be a meaningful advancement for the treatment of MPS II patients," commented
Additional data will be presented at an upcoming medical conference in early 2020.
Following review of the safety and efficacy data from all three patients in Cohort 1, the Independent Data Monitoring Committee for the Phase I/II study of RGX-121 approved the continuation and dose escalation into Cohort 2. Subsequently, RGX-121 was administered to the first patient in Cohort 2 at a dose of 6.5x1010 GC/g of brain mass. Clinical sites are active and recruiting patients, including
"We are pleased that this program is continuing to advance as a potential CNS-specific treatment option for MPS II patients," said
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 (IDS) gene 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 the Phase I/II Clinical Trial of RGX-121
RGX‑121 is being evaluated in a Phase I/II, multi-center, open-label, multiple-cohort, dose‑escalation study in patients with Mucopolysaccharidosis Type II (MPS II) in
About Mucopolysaccharidosis Type II (MPS II)
MPS II 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, 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.
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