Regenxbio announces ‘positive’ interim data from Phase I/II trial of RGX-111

Regenxbio announced positive interim data from the Phase I/II trial of RGX-111 for the treatment of severe Mucopolysaccharidosis Type I. Data from the Phase I/II trial and single-patient Investigational New Drug 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. As 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. 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. 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 is a glycosaminoglycan 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. Patients 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 for chronological or developmental ages 0-42 months, Wechsler Abbreviated Scale of Intelligence for chronological and developmental age greater than six years, and the Vineland Adaptive Behavior Scale. 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 greater than or equal to -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. 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.