Passage Bio has recently announced that Orphan Drug Designation has been granted by the European Commission for PBKR03, a gene therapy for Krabbe Disease. This condition has yet to have any disease-modifying therapies approved. Researchers are hopeful that this therapy could make a difference for patients.
Krabbe disease is a rare lysosomal storage disease. It is caused by a mutated GALC gene. This gene is responsible for encoding a critical enzyme responsible for breaking down psychosine and galactosylceramide. When psychosine accumulates, the death of myelin-producing cells occurs. Nerve cells within the brain as well as within the peripheral tissues are damaged as a result.
Most commonly, the disease presents in infants before they are 6 months old. Patients lose milestones, experience peripheral neuropathy, seizures, weakness, deafness, blindness, and more. Most patients die by the time they reach 2 years of age.
The disease may also present when individuals are between 7-12 months old. These patients have similar symptoms. The median survival is 5 years.
PBKR03 has already been granted Orphan Drug Designation, Fast Track Designation, as well as Rare Pediatric Disease Designation from the FDA.
The therapy is an AVV gene therapy delivered via ICM. Researchers are hopeful that this therapy could treat peripheral nerve manifestations as well as the central nervous system.
Extensive preclinical data has supported the development of this therapy. This data shows that there was meaningful transduction of the peripheral and central nervous systems. Myelination was restored in both the peripheral nerves and the brain.
One study examined Krabbe disease in canines. Researchers found that one singular dose of the therapy led to-
- Normalization of the GALC activity
- Normalization of peripheral nerve conduction velocity
- Reduction of brain inflammation
- Reduction of cerebral spinal fluid psychosine levels
- Improvement of brain myelination
- Increased survival
Researchers will be beginning a Phase 1/2 trial called GALax-C in the first half of 2021. This study will specifically investigate this gene therapy for the early infantile form of the disease (onset before 6 months of age).
This trial is a dose-escalation study. Its primary endpoints are safety as well as tolerability. The researchers will also examine serum GALC levels, cerebrospinal fluid levels, a variety of clinical outcome measures, as well as disease biomarkers.
The team expects that initial safety data will be published in late 2021 or, at the latest, early 2022.