bluebird bio’s cerebral adrenoleukodystrophy (CALD) gene therapy Skysona has moved closer towards EU approval after gaining a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).
The CHMP has recommended marketing authorisation for Skysona (elivaldogene autotemcel, Lenti-D) for the early treatment of CALD in patients under 18 years old with an ABCD1 genetic mutations, and who do not have a matched sibling haematopoietic stem cell (HSC) donor.
bluebird bio’s Skysona is a potential one-time gene therapy designed to add functional copies of the ABCD1 gene into a patient’s hematopoietic stem cells.
Once this functional gene is added to a CALD patient’s 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 is 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.
Currently, the only treatment for the disease is a stem cell transplant, although this carries a significant risk from the high-dose chemotherapy used to prepare patients for the procedure.
Other complications include graft-versus-host (GvHD) disease, which occurs when the transplanted cells recognise the recipient’s cells as foreign and attack them.
In the phase 2/3 Starbeam study evaluating Skysona, 90% of CALD patients met the month 24 major functional disability- (MFD) free survival endpoint as of the last data cutoff date.
MFDs are the six severe disabilities commonly attributed to CALD, which have the most severe effect on a patient’s ability to function independently.
In addition, 26 out of 28 evaluable patients maintained a neurologic function score (NFS) less than or equal to one until month 24, with 24 of those patients having no change in their NFS.
The CHMP’s positive opinion is now due to be reviewed by the European Commission, with a final decision for Skysona expected in mid-2021.