Improvements in Developmental Milestones Observed With GM1 Gangliosidosis Gene Therapy


Data from 2 patients dosed in the Imagine-1 clinical trial were presented in a late breaking session at ASGCT 2022.

New data from the ongoing Imagine-1 clinical trial (NCT04713475) demonstrate good safety and impressive improvements in clinically meaningful end points in patients with GM1 gangliosidosis treated with PBGM01, an investigational gene therapy from Passage Bio.

A single, intra cisterna magna administration of the adeno-associated viral vector serotype Hu68-based therapy, which delivers a functional copy of the human galactosidase beta 1 gene (GLB1) to the cerebrospinal fluid, resulted in documented improvements across all developmental areas, including motor, language, and fine motor skills, in 2 patients with late-onset GM1 in who received the low-dose (3.3 x 1010 GC/g) of the study drug.

The findings were presented by David Weinstein, MD, MMSc, senior vice president, clinical development, Passage Bio, during a late breaker session at the 2022 American Society of Gene and Cell Therapy Annual Meeting, taking place May 16-19, 2022 in Washington, DC.

"Ultimately, we're going to be judged based upon whether we can help these children developmentally, and I'm thrilled to share that the children are making very exciting advances," Weinstein told CGTLive.

Weinstein reported up to 13 and 7 months of follow-up from patient 1 and 2, respectively. As of the data cutoff, no serious adverse events have been reported, and all possibly treatment-related AEs were grade 1, and grade 2 events were deemed unrelated to treatment. No evidence of liver or dorsal root ganglion toxicity have been observed.

Notably, Patient 1, who was 15 months old at time of treatment, gained 12 months developmentally on the Vineland Adaptive Behavior Scale-II over the first 12 months of follow-up, reaching 24 months of developmental milestones. Weinstein reported that the patient is now running, jumping, showing good fine motor skills, and is forming basic sentences.

Patient 2, who was diagnosed later in the disease course at 30 months of age and had demonstrated regression in motor and language skills prior to study enrollment, has advanced 6 months on the Vineland Scale over 7 months of follow-up, and has regained some of the skills lost, including language skills, post-treatment.

In addition, volumetric MRI data from Patient 1 has demonstrated an increase in brain volume at 12-month follow-up compared with baseline, in line with expected development for children ages 0 to 24 months. Notably, the second patient, who was dosed at age 31 months, did not experience this brain volume growth, with a slight decline recorded at 6-month follow-up.

"The fact that we haven't seen the same growth may be due to the child being older. More studies are needed to determine if age or disease severity are going to be important [moving forward]," Weinstein said.

Watch our interview below for more details about the findings.

For more coverage of ASGCT 2022, click here.

Weinstein D, Hastings CA, Day-Salvatore DL, et al. Interim Safety, Biomarker, and Efficacy Data From Imagine-1: A Phase 1/2 Open-label, Multicenter Study to Assess the Safety, Tolerability, and Efficacy of a Single Dose, ICM Administration of PBGM01 in Subjects with Type I (Early Onset) and 10. Type IIa (Late Onset) Infantile GM1 Gangliosidosis (GM1). Presented at: 2022 American Society of Gene and Cell Therapy Annual Meeting; May 16-19, 2022; Washington, DC.
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