REGENXBIO Presents Positive Initial Data from Phase I/II Trial of RGX-111 for the Treatment of Severe MPS I at 18th Annual WORLDSymposium™ 2022
- RGX-111, a potential one-time gene therapy for MPS I, is well-tolerated across two dose levels, with no drug-related serious adverse events
- Biomarker and neurodevelopmental assessments indicate encouraging CNS profile in patients dosed with RGX-111
- Evidence of systemic biomarker activity observed
- Phase I/II trial data are consistent with positive results from an RGX-111 single-patient IND
- Completed dosing of three patients in Cohort 2; Cohort 2 has been expanded to enroll up to 6 additional patients
"This marks our first data presentation from the Phase I/II trial evaluating RGX-111 as a potential one-time gene therapy delivered directly to the central nervous system (CNS) for the treatment of severe MPS I. We are encouraged to see that RGX-111 has been well-tolerated with emerging evidence of CNS biomarker activity and improvements in neurodevelopmental function, which suggest biological activity in the CNS following one-time administration of RGX-111. We also saw emerging evidence of biomarker activity outside of the CNS," said
"MPS I is a rare inherited disorder caused by a mutation in the gene that encodes human α-l-iduronidase (IDUA), an enzyme needed by cells to break down long chains of sugar molecules known as mucopolysaccharides. Current treatment options for MPS I have limitations and can be associated with significant morbidity and mortality," said
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 CNS. The primary endpoint of the trial is to evaluate the safety of RGX-111. Secondary and exploratory endpoints include biomarkers of α-l-iduronidase (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=3). In the single-patient IND for RGX-111, a severe MPS I patient was dosed with 1x1010 GC/g of brain mass.
Data Summary and Safety Update
RGX-111 continues to be well-tolerated in the single-patient IND with no drug-related SAEs as of
CSF Biomarker Data
Data 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 HS in the CSF from baseline was observed through the last timepoint available in all four patients following administration of RGX-111. Measurable IDUA enzyme activity in the CSF was detected after RGX-111 administration in three of the four patients, all of whom had undetectable levels of IDUA activity at baseline.
The patient dosed with RGX-111 under the single-patient IND demonstrated a decrease from baseline in HS in the CSF at 59 weeks after dosing, the last timepoint available. IDUA enzyme activity in the CSF, which was at undetectable at baseline, was detected following RGX-111 administration.
Patients in the Phase I/II trial and the single-patient IND demonstrated encouraging continued neurodevelopment, as measured by age and using developmentally appropriate validated instruments for neurodevelopmental testing, including the Bayley Scales of
Three patients in the Phase I/II trial had neurodevelopmental assessments with at least one post-baseline assessment after administration of RGX-111. Early assessments from the two patients under the age of six years old demonstrated continued skill acquisition within two standard deviations of the normative mean at last assessment on the BSID-III cognition, expressive language and fine motor subtests. One patient in Cohort 1 who entered the trial at the age of 13 years old demonstrated neurodevelopmental improvements as measured by the WASI-II and six of the nine scales of the VABS-III at one year after RGX-111 administration.
The single-patient IND patient demonstrated continued skill acquisition within two standard deviations of the normative mean on the BSID-III cognition, expressive language and fine motor subtests, as well as higher age equivalent scores than available natural history data at last assessment, 20 months after administration of RGX-111.
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, patients dosed with RGX-111 maintained low levels of total urine GAGs at the last timepoint available, regardless of ERT treatment.
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.
RGX-111 is designed to use the AAV9 vector to deliver the α-l-iduronidase (IDUA) gene to the central nervous system (CNS). Delivery of the IDUA gene within the cells in the central nervous system (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. By providing rapid IDUA delivery to the brain, RGX-111 could potentially help prevent the progression of cognitive deficits that otherwise occurs in MPS I patients. RGX-111 has received orphan drug product, rare pediatric disease and Fast Track designations from the
About Mucopolysaccharidosis Type I (MPS I)
MPS I is a rare autosomal recessive genetic disease caused by a deficiency in the lysosomal enzyme alpha-L-iduronidase (IDUA), leading to an accumulation of glycosaminoglycans (GAGs) including heparan sulfate (HS) in tissues which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system (CNS). This 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 hematopoietic stem cell transplant (HSCT) 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 HSCT can be associated with clinically significant morbidity and mortality. Key biomarkers of IDUA enzymatic activity in MPS I patients include its substrate heparan sulfate (HS), which has been shown to correlate with neurocognitive manifestations of the disorder.
About REGENXBIO Inc.
This press release includes "forward-looking statements," within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements express a belief, expectation or intention and are generally accompanied by words that convey projected future events or outcomes such as "believe," "may," "will," "estimate," "continue," "anticipate," "assume," "design," "intend," "expect," "could," "plan," "potential," "predict," "seek," "should," "would" or by variations of such words or by similar expressions. The forward-looking statements include statements relating to, among other things,
View original content to download multimedia:https://www.prnewswire.com/news-releases/regenxbio-presents-positive-initial-data-from-phase-iii-trial-of-rgx-111-for-the-treatment-of-severe-mps-i-at-18th-annual-worldsymposium-2022-301478817.html