REGENXBIO Reports Successful Pre-BLA Meeting with FDA Supporting Accelerated Approval for RGX-121 for MPS II Treatment

REGENXBIO Inc., a biotechnology company, has announced the completion of a Pre-Biologics License Application (BLA) meeting with the U.S. Food and Drug Administration (FDA) for their gene therapy candidate RGX-121, intended to treat Mucopolysaccharidosis Type II (MPS II). This meeting finalized details for the BLA submission, which is set to begin in the third quarter of 2024 using the accelerated approval pathway.

The FDA has expressed support for using cerebrospinal fluid (CSF) levels of heparan sulfate (HS) D2S6 as a surrogate endpoint to predict clinical benefit, an approach that could expedite RGX-121’s approval. Discussions also covered manufacturing processes, non-clinical aspects, and the device delivery system, along with a planned confirmatory study to validate clinical outcomes.

REGENXBIO has confirmed that the commercial and clinical drug materials for RGX-121, produced with their proprietary NAVXpress™ platform, are comparable. Furthermore, an inspection of REGENXBIO’s Manufacturing Innovation Center by the FDA is anticipated in the first half of 2025. A confirmatory trial for RGX-121 is scheduled to start in the second half of 2025, with the potential FDA approval possibly granting a Rare Pediatric Disease Priority Review Voucher the same year.

Curran Simpson, Chief Operating Officer of REGENXBIO and future President and CEO, remarked on the significance of this milestone, emphasizing the alignment with the FDA on crucial BLA elements and the readiness of their manufacturing facility. This progress is also expected to benefit their other rare disease program, RGX-202, aimed at treating Duchenne muscular dystrophy.

Dr. Matthew Ellinwood, Chief Scientific Officer of the National MPS Society, highlighted the urgent need for new treatments for MPS II, particularly those addressing neurocognitive impairments. He expressed optimism about the positive biomarker data, neurodevelopmental outcomes, and systemic results for RGX-121, which could significantly impact affected families.

Earlier this year, REGENXBIO presented topline results from the Phase I/II/III CAMPSIITE® trial for RGX-121, which met its primary endpoint with statistical significance. The trial results were consistent with earlier phases, showing substantial neurodevelopmental benefits compared to historical data. Long-term follow-up indicated that many patients could either discontinue standard enzyme replacement therapy (ERT) or remain ERT-naïve. As of January 2024, RGX-121 was well tolerated in 25 patients across all trial phases. Additional safety and efficacy data from the trial are expected in the latter half of 2024.

The CAMPSIITE® trial is a multicenter, open-label study for boys aged four months to five years with neuronopathic MPS II. The primary endpoint involves measuring glycosaminoglycans (GAGs) in the CSF, specifically HS D2S6, which could serve as a surrogate marker for clinical benefit under the accelerated approval route. The trial also gathers neurodevelopmental and caregiver-reported data.

RGX-121 is an investigational gene therapy that delivers the IDS gene to cells within the central nervous system (CNS), potentially providing a long-term source of the I2S enzyme, which is deficient in MPS II patients. This therapy has received multiple designations from the FDA, including Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy, as well as an advanced therapy classification from the European Medicines Agency.

MPS II, also known as Hunter Syndrome, is a rare genetic disorder caused by a lack of the I2S enzyme, resulting in the accumulation of GAGs like HS in tissues, leading to severe neurological and systemic issues. It occurs in approximately 1 in 100,000 to 170,000 births and presents significant unmet medical needs, particularly for treatments addressing its neurological symptoms.

REGENXBIO, founded in 2009, focuses on developing gene therapies for retinal and rare diseases. Their AAV Therapeutics platform aims to provide one-time treatments that could revolutionize healthcare for millions. Their pipeline includes therapies for wet age-related macular degeneration, diabetic retinopathy, Duchenne muscular dystrophy, and MPS II.