REGENXBIO Inc. (Nasdaq: RGNX) today announced positive interim data from the Phase I/II trial of RGX-111 for the treatment of severe Mucopolysaccharidosis Type I (MPS I). Data from the Phase I/II trial and single-patient Investigational New Drug (IND) application of RGX-111 were presented by Ray Wang, M.D., Campbell Foundation Director of the Multidisciplinary Lysosomal Program, Division of Metabolic Disorders, CHOC Children's Hospital, Department of Pediatrics, University of California, Irvine, at the 19th Annual WORLDSymposium™.
"RGX-111 is our second-most advanced clinical candidate in our neurodegenerative disease pipeline and is part of our '5x'25' strategy to have five gene therapies either on the market or in late-stage development by 2025. We are encouraged to see that this potential one-time gene therapy using our NAV AAV9 vector continues to demonstrate compelling evidence of CNS biomarker activity," said Kenneth T. Mills, President and Chief Executive Officer of REGENXBIO. "In connecting with MPS I families, we understand the need for new treatment options that can impact daily living, and we're pleased to see that most patients in this trial demonstrated continued skill acquisition across multiple neurodevelopmental assessments."
"There is a great need for new treatment options that provide lasting expression of the IDUA enzyme and the reduction of glycosaminoglycans in the central nervous system," said Dr. Wang. "I am encouraged by the emerging clinical profile of RGX-111 based on this data, including the important neurodevelopment gains in cognition, language, fine motor skills and personal and social skills for daily living."
RGX-111 is an investigational one-time gene therapy designed to deliver the gene that encodes the IDUA enzyme using the AAV9 vector. RGX-111 is administered directly to the central nervous system (CNS). The primary endpoint of the trial is to evaluate the safety of RGX-111. Secondary and exploratory endpoints include biomarkers of IDUA enzyme activity in the cerebrospinal fluid (CSF), serum and urine, neurodevelopmental assessments, and caregiver reported outcomes. Patients were treated across two dose cohorts: 1.0x1010 genome copies per gram (GC/g) of brain mass (n=2) and 5.0x1010 GC/g of brain mass (n=6). In the single-patient IND for RGX-111, a severe MPS I patient was dosed with 1x1010 GC/g of brain mass.
REGENXBIO plans to continue having early and frequent communication with regulatory agencies about pathways to expedite the development of its neurodegenerative disease pipeline. In the first half of 2023, REGENXBIO expects to use its Manufacturing Innovation Center to produce RGX-111 commercial-scale cGMP material from its proprietary, high-yielding suspension-based manufacturing process, named NAVXPress™.
Data Summary and Safety DataAs of January 17, 2023, RGX-111 was reported to be well tolerated in the eight patients enrolled in the Phase I/II clinical trial with no drug-related serious adverse events (SAEs). Time of post-administration follow-up ranged from seven to 103 weeks. Two patients in Cohort 1 and three patients in Cohort 2 have completed the 48-week immunosuppression regimen, per the study protocol.
RGX-111 continued to be well-tolerated in the single-patient IND with no drug-related SAEs as of December 12, 2021. Time of post-administration follow-up was 87 weeks. This patient has completed the 48-week immunosuppression regimen, per the study protocol, and continues to receive weekly ERT.
CSF Biomarker DataData from patients in the Phase I/II trial and the single-patient IND indicate positive IDUA biomarker activity in the CNS following one-time administration of RGX-111. Heparan sulfate (HS) is a glycosaminoglycan (GAG) that is a key biomarker of IDUA enzyme activity. In the Phase I/II trial, a decrease in CSF HS was observed through the last timepoint available in the majority of patients following administration of RGX-111. Measurable CSF IDUA enzyme activity was detected after RGX-111 administration in four of the five Phase I/II trial patients and in the single patient IND participant.
Neurodevelopmental DataPatients in the Phase I/II trial and the single-patient IND demonstrated encouraging continued neurodevelopmental skill acquisition, as measured by age and developmentally appropriate validated instruments for neurodevelopmental testing, including the Bayley Scales of Infant Development (BSID-III) for chronological or developmental ages 0-42 months, Wechsler Abbreviated Scale of Intelligence (WASI-II) for chronological and developmental age greater than six years, and the Vineland Adaptive Behavior Scale (VABS-III; across all age groups).
All five patients assessed with BSID-III demonstrated continued developmental skill acquisition on all subsets (cognition, expressive language and fine motor). At the last assessment, four of the five patients had function ≥ -2 standard deviations of the normative mean on the cognition, expressive language and fine motor subtests. Cognitive function in a Phase I/II trial patient and the single IND patient was higher than the age equivalent scores in the available natural history data.
One patient in Cohort 1 who entered the trial at 13 years old demonstrated neurodevelopmental improvements as measured by the WASI-II and showed improvement in the majority of subdomains of the VABS-III at approximately 18 months after RGX-111 administration.
Systemic Biomarker Data Evidence of systemic biomarker activity was observed in patients in both cohorts of the Phase I/II trial and the single-patient IND. Patients who had elevated baseline levels of I0S6 in plasma, a key biomarker of IDUA enzyme activity in MPS I patients, demonstrated decreases in I0S6 levels following administration of RGX-111. In addition, the majority patients dosed with RGX-111 maintained low levels of total urine GAGs at the last timepoint available.
The study findings presented at the WORLDSymposium are available under the Presentations & Publications page in the Media section of the company's website, located at www.regenxbio.com.