Passage Bio, Inc., a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system disorders, today announced that the European Commission (EC) has granted orphan drug designation for the company’s lead gene therapy candidate PBGM01 for the treatment of GM1 gangliosidosis (GM1). PBGM01, an adeno-associated virus (AAV)-delivery gene therapy, has previously been granted Orphan Drug Designation and Rare Pediatric Disease Designation by the U.S. Food and Drug Administration (FDA) for the treatment of GM1. GM1 is a rare and often life-threatening central nervous system disorder with no approved disease-modifying therapies available.
“GM1, most common and severe in infants, results in rapid neurodegeneration and is simply devastating for patients and their families,” said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. “PBGM01 is a potentially transformative gene therapy that may lead to the preservation of neurological function and an improvement in developmental potential and survival in patients with GM1. Receiving orphan drug designation for PBGM01 in the European Union is an important milestone that will propel our efforts to bring this much-needed therapy to waiting patients.”
The EC grants orphan drug designation based on a positive opinion issued by the EMA Committee for Orphan Medicinal Products (COMP). To qualify for orphan designation, an investigational medicinal product must be intended to treat a chronically debilitating or life-threatening condition that affects fewer than five in 10,000 people across the European Union and there is no effective treatment approved in EU. With EMA orphan drug designation, Passage Bio will receive certain benefits and incentives including 10-year market exclusivity for the approved therapeutic indication once PBGM01 receives marketing authorization as well as clinical protocol assistance and reduced regulatory fees.
Passage Bio expects to initiate dosing of PBGM01 in a Phase 1/2 trial late in the fourth quarter of 2020 or early in the first quarter of 2021, with initial 30-day safety and biomarker data expected in the late first half of 2021. 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.
GM1 gangliosidosis (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 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 6 months of life with hypotonia (reduced muscle tone), progressive CNS dysfunction, and rapid developmental regression. Life expectancy for infants with GM1 is two to four years, and infantile GM1 represents approximately 62.5% of the incidence of 0.5 to 1 in 100,000 live births.