The European Medicines Agency (EMA) has accepted a marketing authorisation application (MAA) for bluebird bio’s Lenti-D gene therapy for cerebral adrenoleukodystrophy (CALD).
Bluebird bio’s Lenti-D (eli-cel/elivaldogene autotemcel) is a potential one-time gene therapy designed to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells.
Once this functional gene is added to a CALD patient’s own stem cells, the patient’s body can produce the adrenoleukodystrophy protein (ALDP), which is believed to allow for the breakdown of very-long-chain fatty acids that build up to toxic levels in the brain.
CALD is a progressive and fatal neurodegenerative disease that overwhelmingly affects males. It involves the breakdown of myelin – the protective sheath of nerve cells in the brain that are responsible for muscle control and thinking.
The condition is caused by mutations in the ABCD1 gene that affect the production of ALDP which eventually causes damage to the adrenal cortex and white matter of the brain and spinal cord.
The only current treatment for the disease is a stem cell transplant, but that carries a significant risk from the high-dose chemotherapy used to prepare patients for the procedure. Other potential complications include graft-versus-host (GvHD) disease, when the transplanted cells recognise the recipient’s cells as foreign and attack them.
The MAA was based on data from bluebird bio’s phase 2/3 Starbeam study, as well as supporting data from the ongoing phase 3 ALD-104 study and a long-term follow-up study.
In September 2019, bluebird bio revealed promising data from the phase 2/3 Starbeam study, demonstrating that of those patients who had reached, or would reach, 24 months of follow-up and completed the study, 88% continued to be MFD-free.
MFDs are the six severe disabilities commonly attributed to CALD, which have the most severe effect on a patient’s ability to function independently.
“Data from clinical studies conducted in patients with early CALD suggest eli-cel stabilises the progression of the disease,” said Gary Fortin, senior vice president of severe genetic disease at bluebird bio.
“If approved, eli-cel would represent the first therapy for CALD that uses a patient’s own haematopoietic stem cells, potentially mitigating the risk of life-threatening immune complications associated with transplant using cells from a donor,” he added.