Maria Escolar, MD

“Our hypothesis was that if we treat the patients during this time of myeloablation, we will get less antibody response, and possibly even prolong the therapeutic effect of the gene therapy because we wouldn't have the challenge of the antibodies... And until now, we haven't seen any antibodies, which again, is really encouraging.”

Forge Biologics’ FBX-101 (AAVrh.10-GALC), an investigational gene therapy intended to address unmet needs for patients with Krabbe disease, is currently being evaluated in the phase 1/2 RESKUE clinical trial (NCT04693598). Participants in the trial receive a dose of the gene therapy after first being treated with hematopoietic stem cell transplantation (HSCT), the current standard of care for infants with Krabbe disease. 

Maria Escolar, MD, chief medical officer, Forge Biologics, 

 from the first 2 children treated in the trial at the 29th Congress of the 

European Society of Gene & Cell Therapy (ESGCT)

, held October 11-14, 2022, in Edinburgh, Scotland.

, Escolar discussed the rationale behind the combination therapy approach used in the trial, noting that due to the small window of ideal efficacy for the standard of care, it would not be practical to delay HSCT until after gene therapy administration. She also pointed out the potential benefits of myeloablation during HSCT for preventing an immune response during subsequent administration of the gene therapy. Furthermore, Escolar discussed a synergistic benefit to survival from the combination of HSCT and gene therapy seen in preclinical animal models which the clinical trial investigators hope to replicate for patients. She concluded by outlining the future plans for the clinical evaluation of FBX-101 and noted the importance of expanding newborn screening for Krabbe disease, which is currently only conducted in 10 states in the United States.

Forge Biologics announces updated positive clinical data in RESKUE, a novel phase 1/2 gene therapy trial for patients with Krabbe disease. News release. Forge Biologics. October 11, 2022. 

https://www.forgebiologics.com/2022/10/11/forge-biologics-announces-updated-positive-clinical-data-in-reskue-a-novel-phase-1-2-gene-therapy-trial-for-patients-with-krabbe-disease/

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The chief medical officer of Forge Biologics discussed the potential advantages of the investigational combination therapy approach. 

Maria Escolar, MD, on Combining HSCT With Gene Therapy in Krabbe Disease 

“I think the biggest advantage is that we will probably be addressing the peripheral nerves and the spinal cord, which is something we know that the standard of care doesn't address. [In] preclinical studies … we were able to correct the neuropathy, both pathologically and functionally as measured by nerve conduction velocities in the dogs. So, we're hoping that that we will see the same thing in patients over time.”

While the current standard of care for Krabbe disease, which includes umbilical cord blood transplant, is able to address symptoms in the brain, it does not address the peripheral neuropathy and the demyelination of the spinal cord caused by the disease. As such, there remains significant unmet need for the patient population.

, held October 11-14, 2022, in Edinburgh, Scotland, Maria Escolar, MD, chief medical officer, Forge Biologics, presented data from the phase 1/2 RESKUE clinical trial (NCT04693598) of FBX-101, an investigational gene therapy intended to address unmet needs for patients with Krabbe disease.

, Escolar briefly discussed the limitations of the current standards of care for Krabbe disease and the remaining unmet needs for the patient community. She then gave a topline overview of the data from the 2 patients treated so far in the RESKUE clinical trial that were presented at ESGCT. The data included several promising signs of efficacy, such as an 80-fold increase in the galactocerebrosidase (GALC) enzyme measured in the plasma, and improvements in white matter integrity. In terms of safety, no serious adverse events related to treatment were reported. Escolar concluded by discussing the potential advantages of FBX-101 over the current standard of care.

The chief medical officer of Forge Biologics discussed clinical data presented at ESGCT. 

Maria Escolar, MD

Articles

Maria Escolar, MD, on Combining HSCT With Gene Therapy in Krabbe Disease

Maria Escolar, MD, on Addressing Unmet Needs in Krabbe Disease With Gene Therapy