RARE Daily

Passage Bio Receives Rare Pediatric Disease Designation for GM1 Gangliosidosis Gene Therapy

May 21, 2020

Rare Daily Staff

The U.S. Food and Drug Administration has granted Rare Pediatric Disease designation to Passage Bio’s PBGM01 broadly for the treatment of GM1 gangliosidosis, a rare lysosomal storage disorder. The experimental gene therapy was previously granted Orphan Drug designation.

GM1 gangliosidosis (GM1) is a rare and often life-threatening monogenic recessive 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 rapidly progressing neurodegeneration. GM1 manifests as a continuum of disease and is most severe in the infantile form, which is characterized by onset in the first six months of life by reduced muscle tone, progressive central nervous system (CNS) dysfunction, and rapid developmental regression. Life expectancy for infants with GM1 is two to four years, and infantile GM1 represents approximately 62.5 percent of cases. Currently, there are no approved disease-modifying therapies available.

PBGM01 is an AAV-delivery gene therapy currently being developed for the treatment of infantile GM1. It is designed 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 CNS and critical peripheral organs, suggesting potential treatment for both the CNS and peripheral manifestations of GM1.

Passage Bio anticipates starting a phase 1/2 trial 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 intra cisterna magna, or ICM, in pediatric subjects with infantile GM1. Initial 30-day safety and biomarker data from the trial is expected in the late first half of 2021.

“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, president and CEO of Passage Bio. “We believe that PBGM01 has the potential to restore developmental progression, enabling patients to achieve additional milestones and improve quality of life.”

The FDA grants Rare Pediatric Disease designation for serious or life-threatening diseases with manifestations in individuals aged from birth to 18 years, including access to the FDA’s expedited review and approval process. The designation makes PBGM01 eligible for a Rare Pediatric Disease Priority Review voucher upon approval of the therapy by the FDA. There are no approved therapies for the condition.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Swedish Orphan Biovitrum sold its Priority Review voucher to AstraZeneca for $95 million.

Photo: Bruce Goldsmith, president and CEO of Passage Bio


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