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Abstract Details

RGX-121 gene therapy for severe Mucopolysaccharidosis Type II (MPS II): Interim neurodevelopmental outcomes and biomarker results
Child Neurology and Developmental Neurology
Child Neurology and Developmental Neurology Posters (7:00 AM-5:00 PM)
010
To evaluate the safety and efficacy of CNS-administered gene therapy for severe MPS II
MPS II or Hunter syndrome is caused by a deficiency of iduronate-2-sulfatase (I2S) leading to an accumulation of glycosaminoglycans (GAG) in tissues. Severe MPS II results in irreversible neurocognitive decline and behavioral symptoms that are not addressed by intravenously administered enzyme replacement therapy with recombinant I2S (ELAPRASE®).  
RGX-121 is a recombinant adeno-associated virus serotype 9 capsid (AAV9) containing a human I2S expression cassette (AAV9.CB7.hIDS).  In an MPS II murine model, AAV-mediated transfer of the I2S gene into the cerebrospinal fluid (CSF) demonstrated increased I2S activity in the brain, corrected biochemical changes due to enzyme deficiency, and improved neurobehavioral function.  In this phase 1/2, first-in-human, multicenter, open-label, dose escalation trial (NCT03566043), RGX-121 is administered as a one-time injection into the cisterna magna or lateral cerebral ventricle of participants with severe MPS II ages 4 months to 5 years.  Participants are evaluated for safety, tolerability, and efficacy for 104 weeks after dosing.  Assessments include biomarkers in the CSF, plasma and urine; neurodevelopmental scales (Bayley Scales of Infant and Toddler Development, Vineland Adaptive Behavior Scales); and clinician- and patient-reported outcome measures.   
Six participants have been enrolled in 2 dose cohorts (1.3x1010 and 6.5x1010 genome copies/gram brain).  As of September 16, 2020, RGX-121 is reported to be well-tolerated in all six patients with no drug-related serious adverse events. Encouraging neurodevelopmental and biomarker data have been previously reported, and updated interim results of safety, tolerability and efficacy of RGX-121 will be presented. 

Delivery of the I2S gene within cells in the CNS could provide a permanent source of secreted I2S beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS.
Authors/Disclosures
Paul Harmatz (UCSF Benioff Children's Hospital Oakland)
PRESENTER 		Paul Harmatz has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BioMarin. Paul Harmatz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SOBI. Paul Harmatz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Chiesi. Paul Harmatz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Inventiva. Paul Harmatz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Paradigm. Paul Harmatz has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for JCR. Paul Harmatz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Denali. Paul Harmatz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Homology. Paul Harmatz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Enzyvant. Paul Harmatz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Audentis. Paul Harmatz has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Aeglea. Paul Harmatz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aeglea. The institution of Paul Harmatz has received research support from BioMarin.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Dawn Phillips (Regenxbio) Dawn Phillips has received personal compensation for serving as an employee of REGENXBIO. Dawn Phillips has stock in REGENXBIO.
No disclosure on file
Paulo Falabella (REGENXBIO Inc) No disclosure on file