Maria Escolar, MD, on Continued Positive Results With Gene Therapy and UCBT in Krabbe Disease

“[O]ne thing we have noticed is that the babies that are treated early with gene therapy are following the same trajectory in terms of brain myelination as [unaffected] babies.”

Krabbe disease is a rare genetic disease resulting from a deficiency in the in the galactocerebrosidase (GALC) enzyme, which is responsible for breaking down psychosine. In the absence of GALC, psychosine builds up in the body and causes damage in both the central nervous system (CNS) and peripheral nervous system. If left untreated, Krabbe disease typically causes death by 2 years of age. Standard of care treatment consists of umbilical cord blood transplantation (UCBT), which can help address the CNS symptoms of the disease and allows patients to live to 15 to 20 years of age, but does not substantially impact the peripheral nervous system symptoms. Forge Biologics, which was recently acquired by Ajinomoto, is developing FBX-101, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to be used in combination with UCBT to improve outcomes for patients with Krabbe disease, especially with regard to peripheral nervous system symptoms. Forge is currently conducting the phase 1/2 REKLAIM clinical trial (NCT05739643) for this combination treatment. Promising results from the first 5 children to have been treated in the study so far were recently presented in a late-breaking session at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD, by Maria Escolar, MD, the chief medical officer of Forge Biologics.

After her talk, CGTLive® spoke with Escolar about the background behind the trial and the key results she presented. Escolar went over the promising data generated so far, noting that all the patients treated are improving in gross motor skills and that none of the patients had humoral immune responses to GALC or the AAV vector.

Click here to view more coverage of the 2024 ASGCT Annual Meeting.

REFERENCES
1. Escolar ML, Poe M, Ruiz J, et al. REKLAIM, a phase Ib clinical trial using a novel immune modulation strategy for systemic administration of FBX-101 (AAVrh10.GALC) after umbilical cord blood transplantation for the treatment of infantile Krabbe disease. Presented at: ASGCT Annual Meeting 2024, May 7-10; Baltimore, Maryland. Late-Breaking Abstracts #8.