• Clinical trial expected to enroll children and adults with MPS I
  • Anticipate beginning trial enrollment during the first half of 2018

ROCKVILLE, MD, USA I August 8, 2017 I REGENXBIO Inc. (Nasdaq:RGNX), a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy based on its proprietary NAV® Technology Platform, today announced the Investigational New Drug application (IND) is active for the planned multi-center, open-label, multiple-cohort, dose-escalation Phase I clinical trial of RGX-111 for the treatment of children and adult subjects with Mucopolysaccharidosis Type I (MPS I).

“The goal of the RGX-111 program is to develop a single-dose treatment for MPS I that can prevent the progression of neurocognitive decline experienced by children and some adults, and that can address the shortcomings of the current standard of care, which includes enzyme replacement therapy and bone marrow transplant,” said Olivier Danos, Ph.D., Chief Scientific Officer of REGENXBIO. “We are on track to meet our next program objectives for RGX-111, beginning with trial enrollment in the first half of 2018, and we look forward to working with leading gene therapy researchers and the broader MPS I community on this novel clinical program.”

RGX-111 is being developed under a collaboration with world-renowned gene therapy expert James M. Wilson, M.D., Ph.D., director of the Orphan Disease Center and Gene Therapy Program in the Perelman School of Medicine at the University of Pennsylvania (Penn). Wilson is also a professor of Medicine and Pediatrics.

“In animal studies, treatment with RGX-111 has been shown to restore iduronidase, or IDUA, expression to levels equivalent to or greater than in non-affected animals. The extent of central nervous system correction in our studies was greater than that observed in a previous study of animals treated with bone marrow transplant at similar ages, thus demonstrating that RGX-111 has the potential to be an important and suitable therapeutic option in MPS I,” said Dr. Danos.

RGX-111 has received orphan drug designation as well as rare pediatric disease designation from the U.S. Food and Drug Administration (FDA). Leading international gene therapy and lysosomal storage disease centers are expected to participate in the Phase I trial of RGX-111.

About the Phase I Clinical Trial of RGX-111

RGX-111 will be evaluated in a Phase I, multi-center, open-label, multiple-cohort, dose-escalation study in children and adult subjects with MPS I. Eligible patients must have documented evidence of early-stage neurocognitive deficit due to MPS. Approximately five subjects with MPS I (initial subject >18 years of age, subsequent subjects can be ≥6 years of age) will be treated in two dose cohorts (2 × 109 GC/g brain mass and 1 × 1010 GC/g brain mass), and will receive a single dose of RGX-111 administered by an injection directly in the cerebrospinal fluid (CSF). Patients will receive immunosuppression for the first year after RGX-111 is administered. The primary purpose of the clinical study is to assess the safety and tolerability of RGX-111 at 24 weeks. Primary endpoints include adverse events, certain laboratory measures (including immunologic parameters) and neurological examinations. The study will also assess biomarkers related to iduronidase (IDUA) protein activity within the CSF, serum and urine. Following completion of the primary study period, subjects will continue to be assessed for a total of 104 weeks following treatment with RGX-111. 

About Mucopolysacchardosis Type I (MPS I)

MPS I is a rare autosomal recessive genetic disease caused by deficiency of iduronidase (IDUA), an enzyme required for the breakdown of the polysaccharides in lysosomes. These polysaccharides, called glycosaminoglycans (GAGs), accumulate in tissues of MPS I patients, resulting in characteristic storage lesions and diverse clinical signs and symptoms including in the central nervous system (CNS), which can include excessive accumulation of fluid in the brain, spinal cord compression and cognitive impairment. MPS I is estimated to occur in 1 in 100,000 births. Current disease modifying therapies for MPS I include bone marrow transplant (BMT) and enzyme replacement therapy with a recombinant form of human IDUA administered intravenously. However, intravenous enzyme therapy does not treat the CNS manifestations of MPS I, and BMT can be associated with clinically significant morbidity and mortality.

About RGX-111

RGX-111 is being developed as a novel, one-time, direct-to-CNS treatment for MPS I that includes the NAV AAV9 vector encoding a gene for human IDUA. Delivery of the enzyme that is deficient within cells in the CNS could provide a permanent source of secreted IDUA beyond the blood-brain barrier, allowing for long-term cross-correction of cells throughout the CNS. This strategy could also provide rapid IDUA delivery to the brain, potentially preventing the progression of cognitive deficits that otherwise occurs in MPS I patients.


REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. REGENXBIO’s NAV Technology Platform, a proprietary adeno-associated virus (AAV) gene delivery platform, consists of exclusive rights to more than 100 novel AAV vectors, including AAV7, AAV8, AAV9 and AAVrh10. REGENXBIO and its third-party NAV Technology Platform Licensees are applying the NAV Technology Platform in the development of a broad pipeline of candidates in multiple therapeutic areas.

Note Regarding Penn

Penn has licensed certain Penn-owned AAV technologies to REGENXBIO, including rights related to RGX-111. Dr. Wilson is an advisor to REGENXBIO, and is a founder of, holds equity in, and receives sponsored research funding from REGENXBIO.

SOURCE: Regenxbio