Krabbe Disease Gene Therapy Receives EMA PRIME Designation


Forge Biologics’ FBX-101 previously demonstrated promising safety and efficacy in early data from the phase 1/2 RESKUE clinical trial.

Forge Biologics’ FBX-101 (AAVrh.10-GALC), an investigational adeno-associated viral serotype rh10 (AAVrh10) gene therapy intended to treat Krabbe disease, has received priority medicines (PRIME) designation from the European Medicines Agency (EMA).1

FBX-101 is intended to deliver a functional copy of GALC, the disease-targeted gene, which codes for an enzyme (GALC) that breaks down psychosine and some other sphingolipids. The lack of GALC activity in Krabbe disease leads to a buildup of psychosine that causes demyelination, which in turns leads to worsening symptoms including difficulty swallowing, breathing, developmental delay, vision and hearing loss, and death. FBX-101 is currently being evaluated in the nonblinded, nonrandomized phase 1/2 RESKUE clinical trial (NCT04693598), in which participants receive the gene therapy after first being treated with hematopoietic stem cell transplantation (HSCT), the current standard of care. The dose escalation trial is recruiting children from birth to 12 months of age.

Maria Escolar, MD, chief medical officer, Forge Biologics, presented updated data 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.2 In an interview with CGTLive late last year, Escolar shared some of the promising signs of efficacy seen in these patients, including an 80-fold increase in GALC enzyme levels measured in plasma and improvements in white matter integrity. She also noted that no serious adverse events related to the treatment were observed. Forge Biologics has additionally reported that patients in the trial’s low dose cohort showed reduced psychosine levels and improved motor development in comparison to untreated patients or patients treated only with HSCT.1

“An update on our first cohort data demonstrates that intravenous FBX-101 after HSCT infusion was safe and well tolerated, including increased GALC enzyme activity in plasma and cerebrospinal fluid, normal myelination of white matter, and normalization of motor development,” Escolar said in an October 2022 statement.2 “The results are exciting and give us hope for patients suffering from Krabbe disease who typically do not live past 2 years of age untreated.”

FBX-101 previously received orphan drug designation (ODD)from the EMA in September of 2021.3 This was the therapy’s second ODD, with it previously having been granted ODD by the FDA in February 2021, along with rare pediatric disease and fast track designations.4 Forge Biologics also noted in September 2021 that the company had received positive feedback from the FDA on its AAV production processes, proprietary plasmids, and Ignition HEK293 suspension cell line.3

“We are grateful to the EMA for recognizing FBX-101 as a potentially transformative medicine for patients living with this life-threatening and devastating disease,” Christopher Shilling, senior vice president of regulatory affairs and quality, Forge Biologics, said in a statement regarding the news of the PRIME designation.1 “Through the enhanced interactions with the EMA granted by the PRIME designation, we will advance and expedite the development of FBX-101 as the leading worldwide gene therapy for patients with Krabbe disease.”

1. Forge Biologics receives priority medicines (PRIME) designation from the European Medicines Agency (EMA) for novel gene therapy FBX-101 for the treatment of patients with Krabbe disease. News release. Forge Biologics. 
2. 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. 
3. Forge Biologics announces regulatory updates from FDA and EMA, accelerating manufacturing and clinical trial momentum. News release. Forge Biologics. September 20, 2021. 
4. Forge Biologics receives FDA fast track, orphan drug, and rare pediatric disease designations for FBX-101 gene therapy for patients with Krabbe disease. News release. Forge Biologics Inc. February 16, 2021. 
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