Infantile Krabbe disease (IKD), a severe neurodegenerative disorder caused by galactocerebrosidase (GALC) deficiency, leads to death by 2 years. Hematopoietic stem cell transplantation (HSCT) improves outcomes in asymptomatic infants, but motor function declines due to peripheral neuropathy. FBX-101 is an AAVrh10-hGALC vector designed to rescue peripheral nerve disease.

RESKUE and REKLAIM are Phase 1/2 dose-escalating gene therapy clinical trials to evaluate safety and efficacy of FBX-101 administered 21-60 or more than 90 days after HSCT, respectively, in patients with IKD and Late-IKD. Cohort 1 subjects receive an IV dose of 1.6x10¹³ vg/kg of FBX-101 and are monitored for 2 years post administration.

Two subjects have received FBX-101 in RESKUE. FBX-101 was well tolerated, with no treatment-related serious adverse events (including no treatment-related liver enzyme elevations) observed up to Month 12 and Month 9. No antibodies to AAVrh10 have developed, and both subjects have engrafted with full chimerism. We report a significant increase in plasma and CSF GALC enzyme activity, improvement in motor skills, and normal white matter growth in the brain measured by MRI-DTI.

In REKLAIM, one subject has been dosed with no treatment-related adverse events and normalization of plasma GALC levels three months after FBX-101 administration.

Administration of FBX-101 after HSCT represents a novel gene therapy strategy that leverages the immune- and myeloablation after UCBT, resulting in an immune environment that allows efficient AAV transduction, prevents development of antibodies against the vector and ensures that sufficient GALC enzyme is delivered to sustainably support both brain and peripheral nerve development.