REGENXBIO Reveals Positive Long-Term Data for RGX-121 at Pivotal Dose

REGENXBIO Inc., a clinical-stage biotech company, has announced positive outcomes from their Phase I/II/III CAMPSIITE trial of RGX-121, aimed at treating Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome. The announcement was made at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium 2024.

The comprehensive data from the CAMPSIITE trial underscores RGX-121's potential as the first gene therapy and one-time treatment for MPS II. Notably, RGX-121 appears to address the neurocognitive decline associated with the disease, positioning it as a potential first-line treatment for patients with neuronopathic conditions in the USA.

Dr. Steve Pakola, Chief Medical Officer of REGENXBIO, highlighted the promising data presented at SSIEM, showing systemic activity and long-term reductions of cerebrospinal fluid (CSF) D2S6. This biomarker is crucial in assessing brain disease activity in MPS II. He emphasized that the therapy could transform the disease's trajectory by restoring the missing gene in boys with Hunter syndrome, potentially improving brain function and systemic symptoms significantly.

Key findings from the CAMPSIITE trial include an 85% median reduction in CSF levels of heparan sulfate (HS) D2S6 among patients receiving the pivotal dose level, with reductions sustained for up to two years. Earlier primary endpoint outcomes from the trial showed statistically significant results. Data from the dose-finding phase revealed that most patients exhibited improved neurodevelopmental function compared to natural history data, with effects lasting up to four years.

A significant aspect of the trial was the discontinuation of standard intravenous enzyme replacement therapy (ERT) for many patients. At the pivotal dose level, 80% of patients were ERT-free for over 18 months post-dosing. In dose level 2, 71% remained ERT-free for almost three years. As of early 2024, RGX-121 has been well-tolerated in 25 patients across various trial phases.

Dr. Roberto Giugliani, Professor of Medical Genetics, expressed optimism about the therapy's potential to surpass natural disease progression in neurocognitive development and reduce dependence on ERT for multiple years. He looks forward to the program advancing towards approval.

REGENXBIO plans to submit a rolling Biologics License Application (BLA) using the accelerated approval pathway in Q3 2024, using CSF D2S6 as a surrogate endpoint likely to predict clinical benefit. A successful BLA could lead to a Priority Review Voucher in 2025.

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 CSF glycosaminoglycans (GAGs), with HS D2S6 as a surrogate marker for clinical benefit. The trial uses REGENXBIO's NAVXpress™ manufacturing process.

RGX-121 is an AAV therapeutic designed for one-time treatment of boys with MPS II. It delivers the IDS gene to cells in the central nervous system (CNS), potentially providing a long-term source of I2S protein beyond the blood-brain barrier. RGX-121 has received multiple designations from the U.S. Food and Drug Administration and the European Medicines Agency.

MPS II, or Hunter Syndrome, is a rare genetic disorder caused by a deficiency in the enzyme iduronate-2-sulfatase (I2S), leading to an accumulation of GAGs in tissues, causing cell, tissue, and organ dysfunction, including in the CNS. It affects approximately 1 in 100,000 to 170,000 births, with severe forms showing developmental delays by 18 to 24 months. There is a critical need for treatments addressing the neurological manifestations of MPS II.

REGENXBIO is a leading biotech firm founded in 2009, specializing in AAV Therapeutics for retinal and rare diseases. Their platform has already treated thousands, including those with spinal muscular atrophy using Novartis’ ZOLGENSMA. Their gene therapy aims to revolutionize healthcare delivery, offering significant benefits for millions.