New Medicines

GM1 gangliosidoses


New molecular entity
Passage Bio
Passage Bio

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials
Mar 21FDA grants fast track status [4].
Oct 20Granted orphan drug status in the EU [4].
May 20FDA grants Rare Pediatric Disease (RPD) designation to PBGM 01 [4].
Apr 20FDA grants orphan drug status to PBGM 01 for the treatment of infantile GM1 gangliosidosis [4].


An adeno-associated virus (AAV) vector delivery gene therapy using a next generation AAVhu68 capsid administered through intra cisterna magna (ICM) to deliver a functional GLB1 gene encoding β gal to the brain and peripheral tissues. By reducing the accumulation of GM1 gangliosides, PBGM 01 has the potential to reverse neuronal toxicity, thereby restoring developmental potential.
GM1 gangliosidosis is an inherited lysosomal storage disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. The condition may be classified into three major types based on the general age that signs and symptoms first appear: classic infantile (type 1); juvenile (type 2); and adult onset or chronic (type 3). GM1 gangliosidosis is caused by mutations in the GLB1 gene [1]. GM1 gangliosidosis is estimated to occur in 1 in 100,000 to 200,000 newborns [2].
GM1 gangliosidoses

Trial or other data

Feb 22Interim data from the PI/II Imagine-1 trial showed developmental improvement in assessments of treated patients. Improvement in all developmental areas were observed for patient 1, at six months. Through the six months following administration of low dose PBGM 01, overall development age tracked closely to chronologic age progressing from 12 months at baseline to 17 months, at the six months. Overall development age progressed from 12 months at study start to 23 months at the nine-month interim assessments, approaching the patient’s chronologic age of 24 months. At the three-month assessments for patient 2, improvement was observed for motor, receptive language, and cognitive domains. Despite a severe developmental delay at study start, the overall development age progressed during the three months following administration of PBGM 01 from 7 months at baseline to 9 months. Also, at month four, following the three-month Vineland and Bayley assessments, patient 2 was clinically observed to have regained previously lost developmental milestones, such as the ability to walk and use expressive language [4].
Mar 21PI/II Imagine-1 trial to evaluate the safety, tolerability and efficacy of a single dose of PBGM 01 delivered into the cisterna magna of subjects with type 1 (early onset) and type 2a (late onset) infantile GM1 gangliosidosis starts (NCT04713475; PBGM01-001). The single-arm, dose escalation, adaptive design, open-label study intends to enrol 20 children aged 4 months to 36 months in the US, Brazil, Canada, Turkey and the UK (at Great Ormond Street Hospital). In Part 1 of the study, two dose levels of PBGM01 will be studied separately in patients with either Type 1 or Type 2a GM1 gangliosidosis (see table below). The cohorts for patients with Type 1 and Type 2a will be assessed independently from each other. Part 1 will enroll a total of four cohorts, enrolled sequentially with separate dose-escalation cohorts for Type 1 GM1 and Type 2a GM1. Enrollment will initiate in Cohort 1. Following completion of Cohort 1, simultaneous enrollment in Cohort 2 and Cohort 3 will occur. Cohort 4 will follow completion of cohort 3. Part 2 of the study will test the safety and efficacy of PBGM01 in confirmatory cohorts for Types 1 and Type 2a GM1 gangliosidosis with a dose chosen based on the data obtained in part 1 of the study. This will be a 2-year study with a 3-year safety extension. Primary outcomes include safety and change in nerve conduction velocity and amplitude from baseline on nerve conduction studies; collection of these data will complete Feb 26 [3].