Company: RGNX
Filing Date: 2025-03-13
Form Type: 10-K
Source: 0000950170-25-038770
Chunk: 85

Company: REGENXBIO Inc.
Filing Date: 2025-03-13
Form: 10-K
Item: Item 1
Chunk 85
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 not treat CNS manifestations of the disease because the enzyme cannot cross the blood-brain barrier. We believe that specific treatment to address the neurological manifestations of MPS II and prevent or stabilize cognitive decline remains a significant unmet medical need.

RGX‑121 is designed to use the NAV AAV9 vector to deliver the human IDS gene to cells in the CNS. Delivery of the gene therapy and expression of the enzyme that is deficient within cells in the CNS could provide a permanent source of secreted I2S enzyme on the CNS side of the blood-brain barrier, allowing for long-term cross-correction of cells throughout the CNS. We believe this strategy could provide rapid I2S enzyme delivery to the brain, potentially preventing the progression of cognitive deficits that otherwise occur in MPS II patients.

We have received orphan drug product designation, rare pediatric disease designation, regenerative medicine advanced therapy (RMAT) and Fast Track designation from the FDA, as well as orphan designation and advanced therapy medicinal products (ATMP) classification from the EMA for RGX‑121.

Clinical Development of RGX‑121 for the Treatment of MPS II

CAMPSIITE® is a Phase I/II/III multicenter, open-label trial enrolling boys with MPS II, aged 4 months up to 5 years of age. 

In February 2024, we reported that the pivotal phase of the CAMPSIITE trial achieved its primary endpoint, Proportion of Patients with cerebrospinal fluid (CSF) D2S6 below maximum attenuated level at W16. Accurate and sensitive measurements of CSF GAGs, such as HS D2S6, 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. MPS II patients treated with RGX-121 achieved decreased CSF levels of D2S6 below maximum attenuated disease levels at 16 weeks (p value of 0.00016). Patients receiving RGX-121 demonstrated an 86% median reduction in D2S6, approaching normal levels. Pivotal results were consistent with data from the dose-finding phase of CAMPSIITE, in which the majority of patients were shown to be exceeding expectations in neurodevelopmental function compared to natural history data up to four years.

The pivotal program used commercial-scale cGMP material from our proprietary, high-yielding