Last week, the US Food and Drug Administration’s (FDA) Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) unanimously endorsed a new therapy for early active cerebral adrenoleukodystrophy (CALD). The new treatment, elivaldogene autotemcel (eli-cel), would be the first gene therapy for CALD.
Florian Eichler, MD, Director of the Mass General Leukodystrophy Service, collaborated with transplant experts at Boston Children’s Hospital and Bluebird Bio to design this trial using an ex vivo lentiviral gene therapy approach. This therapy is similar to the currently available treatment, allogeneic hematopoietic stem cell transplant (allo-HSCT), but with the noted difference of using autologous cells – that is, the patient’s own cells – that have undergone gene correction. Using autologous cells avoids the risks of transplants from other people and could be especially valuable for patients who do not have a close sibling donor match.
CALD is the most severe form of adrenoleukodystrophy, a rare neurodegenerative disease that primarily affects boys. Today, it is treatable only with allo-HSCT, a therapy with severe side effects that can be exacerbated if a patient does not have a closely-matched sibling donor.
Eli-cel is not without its own risks, including myelodysplastic syndrome, a rare malignancy in which blood cells fail to form properly. There is ongoing work to understand this complication and treat it effectively. However, the FDA panel recommended it for approval because they believe that the benefits outweigh the risks at this time.
Eli-cel now moves to the next phase of the approval process, with review expected to be complete in September 2022.
Dr. Eichler is optimistic about the news. “We will need to monitor for myelodysplastic syndrome and reassess over time,” he says, but the day “feels historic.”