PHILADELPHIA—Passage Bio, Inc. has announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease designation to PBGM01 for the treatment of GM1 gangliosidosis (GM1). PBGM01 was also previously granted Orphan Drug designation.
PBGM01 is an AAV-delivery gene therapy being developed for the treatment of infantile GM1. The therapy utilizes a next-generation AAVhu68 capsid administered through the intra-cisterna magna (ICM), in order to deliver a functional GLB1 gene encoding β-gal to the brain and peripheral tissues. By reducing the accumulation of GM1 gangliosides, PBGM01 has the potential to reverse neuronal toxicity, thereby restoring developmental potential.
In preclinical models, PBGM01 has demonstrated broad brain distribution and wide uptake of the β-gal enzyme in both the central nervous system (CNS) and critical peripheral organs. This suggests that PBGM01 is a potential treatment for both the CNS and peripheral manifestations of GM1.
“This is the second regulatory designation we have received from the FDA for our lead program in GM1, and reflects the high unmet need in this patient population,” said Bruce Goldsmith, Ph.D, president and chief executive officer of Passage Bio. “As a company we are committed to developing therapies that transform the lives of patients suffering from serious life-threatening CNS disorders. We believe that PBGM01 has the potential to restore developmental progression, enabling patients to achieve additional milestones and improve quality of life. We look forward to advancing PBGM01 into clinical testing later this year.”
GM1 is a rare and often life-threatening monogenic recessive lysosomal storage disease caused by mutations in the GLB1 gene, which encodes lysosomal acid beta-galactosidase (β-gal). Reduced β-gal activity results in the accumulation of toxic levels of GM1 ganglioside in neurons throughout the brain, causing neurodegeneration that progresses rapidly.
GM1 manifests as a continuum of disease and is most severe in the infantile form, which is characterized by onset in the first 6 months of life with hypotonia, progressive CNS dysfunction and rapid developmental regression. Life expectancy for infants with GM1 is two to four years. Currently, there are no approved disease-modifying therapies available.
Passage plans to initiate a Phase 1/2 trial for PBGM01 for the treatment of GM1 in the fourth quarter of 2020. The trial will be an open-label, dose escalation study of PBGM01, administered by a single injection into the ICM in pediatric GM1 subjects. Initial 30 day safety and biomarker data is expected in the late first half of 2021.