PHILADELPHIA, PA — Passage Bio, Inc. (Nasdaq: PASG) recently announced updated clinical data from Imagine-1, a Phase 1/2 study of PBGM01, a gene therapy for GM1 gangliosidosis (GM1), presented Friday at the 19th Annual WORLDSymposium™. Imagine-1 is a global, open-label, dose-escalation study of the AAVhu68 gene therapy PBGM01 delivered by intra-cisterna magna (ICM) injection in four cohorts of pediatric subjects with early and late infantile GM1 Gangliosidosis (GM1). GM1 is a rare, fatal lysosomal storage disease in which mutations in the GLB1 gene result in very low activity of the enzyme beta-galactosidase (β-Gal). The presentations at the WORLDSymposium™ include safety, biomarker and efficacy data from six treated patients in the first three cohorts of the study.
“We are pleased to share promising data from the first six patients in our Imagine-1 study that continue to demonstrate PBGM01 has exerted a biological effect in patients with infantile forms of GM1 gangliosidosis,” said William Chou, M.D., chief executive officer of Passage Bio. “At this interim analysis, all treated patients showed stabilization of MRI severity scores, a potential marker of disease severity and progression measured by structural damage of the brain. Furthermore, patients exhibited decreases in urine levels of the β-Gal substrate Dp5, an exploratory biomarker of peripheral β-Gal activity. These data are supported by the favorable safety profile of PBGM01 and bolster our confidence in PBGM01 as a potential treatment option for GM1 patients. We look forward to continued advancement of our Imagine-1 study and sharing new data from Cohort 4 by mid-year.”
The data presented at the 19th Annual WORLDSymposium™ build upon the positive interim safety and biomarker data announced by the company in December 2022, which showed that PBGM01 administration was well tolerated and had a favorable safety profile, with no treatment-related serious adverse events, no complications related to ICM delivery and no evidence of dorsal root ganglion (DRG) toxicity. Moreover, PGBM01 administration resulted in dose-dependent increases in CSF β-Gal activity, as well as dose-dependent decreases in CSF GM1 ganglioside levels.
Updated interim results from cohorts 1-3 of the Imagine-1 study
Magnetic Resonance Imaging (MRI) Severity Score
- The MRI severity score, a novel scoring metric, can be used to assess treatment effects on brain volume and white matter integrity for GM1 patients based on baseline and follow-up brain MRI scans. This score measures cerebral and cerebellar atrophy, abnormalities in white matter, and signal abnormalities in the basal ganglia and hippocampi to determine levels of structural damage.
- Natural history data from late infantile GM1 patients showed MRI severity scores increased in the majority of children over a follow-up period of six months to four years.
- Preliminary data over a follow-up period of six to 12 months showed PBGM01 administration was associated with stabilization of MRI severity scores in all treated patients.
- PBGM01 administration resulted in decreases in β-Gal substrate Dp5 levels in urine, suggesting ICM delivery of PBGM01 results in peripheral β-Gal activity.
- Both patients who received the high dose (Cohort 2, late infantile) exhibited prominent decreases in urine Dp5 levels.
- Patients with high baseline levels treated with the low dose of PBGM01 exhibited decreases in urine Dp5 levels.
A copy of the data presentation isavailable on the Investor Events and Presentations page of the Passage Bio corporate website.
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