Cautious Optimism for GM1 Gangliosidosis Gene Therapy: David Weinstein, MD

"I’m excited by [the data] but I want to be careful to not read too much into it until we have more more long-term data. But this is extremely encouraging. This is one of the first examples of intracisternal magna approach. And we're seeing that the procedure can be done safely and can have a remarkable impact, both on biomarkers and clinically."

Intracisternal magna administration of PBGM01 has demonstrated preliminary efficacy in achieving and regaining developmental milestones in GM1 gangliosidosis in the first 2 children dosed in the phase 1/2 IMAGINE-1 trial (NCT04713475). These data were presented by David Weinstein, MD, senior vice president, clinical development, Passage Bio, at the 18th Annual WORLDSymposium, February 7-11, 2022 in San Diego, CA.

Investigators observed no serious adverse events (AEs) and mostly mild AEs unrelated to treatment. Both patients dosed exhibited substantial (1.5- and 4.8-fold) and durable increases in cerebrospinal fluid CSF β-gal, as well as stabilized or decreased GM1 ganglioside levels. Investigators also observed developmental gains substantially differing from natural history on the Vineland-II and Bayley-III scales. The first patients in the second (early-onset) and third cohort (high-dose) have now also been dosed.

CGTLive spoke with Weinstein to learn more PBGM01 and the IMAGINE-1 trial. He discussed the positive safety findings and the initial efficacy seen so far in the trial, including promising biomarker activity.

REFERENCE

Weinstein DA, Day-Salvatore DL, Ficicioglu C, et al. Safety, biomarker and preliminary efficacy results following ICM administration of PBGM01 in children with late onset infantile GM1-gangliosidosis. Presented at: 18th Annual WORLDSymposium, February 7-11, 2022; San Diego, CA. Poster #LB-71