REGENXBIO's MPSII Gene Therapy Charts Course to Approval


The FDA will consider RGX-121's BLA in an accelerated approval pathway.

REGENXBIO has announced their plans to file a biologics license application (BLA) for RGX-121 with the accelerated approval pathway for mucopolysaccharidosis type II (MPS II), also known as Hunter Syndrome.1

"We are pleased to share that our recent discussions with the FDA support our plans to submit a BLA for RGX-121 in 2024 using the accelerated approval pathway, which was created to allow for expedited development of drugs that treat serious conditions and provide a meaningful advantage over available therapies based on a surrogate endpoint," Kenneth T. Mills, president and chief executive officer, REGENXBIO, said in a statement.1 "We believe RGX-121 for the treatment of Hunter Syndrome has demonstrated emerging positive impact on neurodevelopmental function, and we intend to advance this program as quickly as possible with the aim of providing a much-needed new treatment option for the MPS II community."

RGX-121 is currently being evaluated in a phase 1/2 clinical trial (NCT04571970), which has been expanded into a pivotal phase 1/2/3 trial called CAMPSIITE. CAMPSIITE is currently recruiting up to 10 boys aged 4 months up to 5 years globally across sites in the US, Brazil, and Canada. It will evaluate endpoints including changes from baseline of glycosaminoglycans (GAGs) in the cerebrospinal fluid (CSF) at 4 months post-treatment and neurodevelopmental data and caregiver-reported outcomes.

"MPS II patients face irreversible neurodevelopmental decline that significantly impacts a child's daily life and life expectancy," principal investigator Paul Harmatz, MD, professor, University of California – San Francisco Department of Pediatrics, added to the statement.1 "Current therapies are inadequate, so we are excited to be a part of this study and eager to see the potential impact on patients."

READ MORE: Gene Therapy May Slow Progression of MPS Type IIIA

Participants are now being dosed in CAMPSIITE with 2.9x1011 GC/g of brain mass of RGX-121, which is the same dose being evaluated in cohort 3 of the phase 1/2 trial portion. The gene therapy product is manufactured using REGENXBIO’s NAVXPress manufacturing process.

"The accelerated approval pathway gives patients access to potentially life-changing therapeutics sooner, which is why it is a critical tool for the over 7,000 rare diseases, most of which lack FDA-approved treatments," Joseph Muenzer, MD, PhD, Bryson Distinguished Professor in Pediatrics Genetics, and director, MPS Research and Treatment Program, University of North Carolina at Chapel Hill, added to the statement.1 "Boys with MPS II do not have time to wait. I am encouraged by FDA's commitment to advance therapies for rare diseases and their willingness to consider this important pathway for RGX-121."

RGX-121 uses the NAV adeno-associated virus (AAV) 9 vector to deliver the human iduronate-2-sulfatase gene (IDS) encoding iduronate-2-sulfatase (I2S) enzyme to the central nervous system (CNS). This is designed to allow correction of CNS cells to reduce GAGs. The therapy has received orphan drug, rare pediatric disease, and fast track designations from the FDA.

"MPS II families are in need of a treatment option that can address the neurodevelopmental decline associated with this disease that available enzyme replacement therapies cannot," Terri Klein, president and chief executive officer, National MPS Society, added to the statement.1 "We are encouraged by today's announcement and the hope that a one-time gene therapy offers this community."

Positive interim data from the phase 1/2 trial were presented at the 18th Annual WORLDSymposium, February 7-11, 2022, by Roberto Giugliani, MD, PhD.2 Presented data were from 13 participants with MPSII as of December 20, 2021. Immunosuppression was discontinued in all 8 eligible participants. No treatment-related serious adverse events (AEs) were observed as of the data cut-off date.

Investigators found dose-dependent reductions in heparan sulfate in CSF in the majority of participants as well as GAG reductions and I2S protein concentration increases. Bayley Scale of Infant and Toddler Development scores revealed improvements in cognition, expressive language, and fine motor skills and improvements were also seen in maladaptive behaviors and improvements in toileting skills via the Vineland scale. REGENXBIO plans to share new data on RGX-121 at the Society for the Study of Inborn Errors of Metabolism Annual Symposium on August 31, 2022.1

1. REGENXBIO announces intention to file a biologics license application using the accelerated approval pathway for RGX-121, an AAV therapeutic for the treatment of MPS II. News release. REGENXBIO. August 3, 2022.
2. Hermatz P, Escolar M, Ficicioglu C, et al. RGX-121 gene therapy for the treatment of severe mucopolysaccharidosis type II (MPS II): Interim analysis of data from the first in-human study. Presented at: 18th Annual WORLDSymposium, February 7-11, 2022; San Diego, CA.
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