Achieving Developmental Milestones With GM1 Gangliosidosis Gene Therapy: David Weinstein, MD

“The second child had gained milestones, including walking and talking, but unfortunately had lost them by the time the child got into the study... The child was treated in September, so we only have very limited data, but the child has begun walking again and is using specific terms like mom and dad again. It's been remarkable... I was in the academic world for 30 years, and I never saw a child with any condition regain milestones after losing them. So, we're very excited to share these results to get the results out there.”

PBGM01 administered to the intracisternal magna has shown preliminary efficacy in achieving and regaining developmental milestones in the first 2 children with GM1 Gangliosidosis dosed in the phase 1/2 IMAGINE-1 trial (NCT04713475). New data from the trial 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.

The therapy has been well tolerated, with no serious adverse events (AEs) and mostly mild AEs unrelated to treatment. Both patients dosed exhibited substantial (1.5- and 4.8-fold) increases in cerebrospinal fluid CSF β-gal that have remained elevated. GM1 ganglioside levels stabilized or decreased in these patients. Developmental gains substantially differing from natural history were seen 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.

GeneTherapyLive spoke with Weinstein to learn more about the data presented from the IMAGINE-1 trial. He discussed the encouraging data in biomarkers, safety, and development seen so far in the 2 patients dosed.

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