AB-205-301 is a Phase 3 clinical study, intended to determine if the experimental therapy AB-205 is safe and effective for US FDA approval in its use with blood stem cell transplants used to cure lymphoma. AB-205 contains venous lining (endothelial) cells from umbilical cords (donated by mothers after a healthy delivery) that are genetically modified using a prosurvival gene called E4ORF1. Umbilical cord endothelial cells have characteristics that can aid in recovery of the body and damaged tissue, but by themselves are not useful because they are unstable and few in numbers. E4ORF1 gene insertion makes these cells stable and increases the reparative potency, thus allowing them to be used as regenerative medicine.
The intention of this Phase 3 study was to lower the rate of severe toxicities (severe mucositis, nausea, vomiting or diarrhea) associated with stem cell transplantation used to cure blood cancers, such as lymphoma. The rate of severe complications, which requires hospitalization for treatment, was estimated to be approximately 40%. This study enrolled 140 patients, randomly assigned to either AB-205 or placebo. Otherwise, all of the participants received the same state-of-the-art stem cell transplantation for lymphoma at prestigious US cancer centers. The study was conducted from 2022 to 2023.
Unfortunately, AB-205 did not reduce the rate of severe transplant-related toxicities in this study, unlike the earlier Phase 2 study, where it showed major reductions. Both groups (AB-205 vs placebo) reported the expected severe toxicity rate of 40-50%.
AB-205 was deemed to be safe by an independent Data Safety Monitoring Board of the study. AB-205, given as intravenous infusion, was well tolerated by patients, including in the elderly (> 65 years old). There appeared to be some tendency that patients who received AB-205 felt better; also, patients who had AB-205 in their blood stream 2 days out tended to have lower toxicity rates (although this group was small in numbers). Further analysis and research may be helpful to understand why the positive Phase 2 results were not verified in this Phase 3 study.
Because of the solid safety profile of AB-205, further clinical research in other conditions or diseases that can benefit from a regenerative medicine to accelerate healing and recovery would be warranted. The restoration or acceleration of the body’s capacity to heal, often reduced with aging or lost with disease, is a very important area of regenerative medicine research. Hence AB-205 and related therapies deserve to be further tested in other conditions, especially chronic non-healing diseases.
