bluebird bio has revealed new data from its clinical development programme for Lenti-D gene therapy in cerebral adrenoleukodystrophy (CALD).
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 adrenoleukodystrophy protein (ALDP), which eventually causes damage to the adrenal cortex and white matter of the brain and spinal cord.
bluebird bio’s Lenti-D (eli-cel/elivaldogene autotemcel) is a potential one-off gene therapy designed to add functional copies of the ABCD1 gene to a patient’s own hematopoietic stem cells.
Once this functional gene is added to a CALD patient’s stem cells, the body can produce ALDP, which is believed to allow for the breakdown of very-long-chain fatty acids that build up to toxic levels in the brain.
New data from the phase 2/3 Starbeam study (ALD-102) study showed that, out of the patients who reached month 24, 90% met the primary endpoint and continued to be alive and free from major functional disabilities (MFD) at two years of follow-up.
In addition, there was no evidence of MFDs throughout nearly seven years of follow-up in the 27 patients who completed the study.
Data from the LTF-304 study also showed that 14 patients have reached their five-year follow-up visit, and this includes seven patients who have reached their six-year follow-up visit.
bluebird bio added that the two patients from the Starbeam study who had not reached month 24 have also shown no evidence of MFDs.
The company also reported data on several secondary and exploratory efficacy outcomes, including changes in neurologic function score (NFS) – a 25-point score used to evaluate the severity of gross neurologic dysfunction.
According to bluebird bio, out of the 32 patients treated with Lenti-D, 31 had stable NFS at the last available visit and 23 patients maintained an NFS of 0 – this indicated that there is no observed impairment in neurologic functions assessed on the 25-point scale.
On the safety front, bluebird bio also said that no events of acute or chronic graft-versus-host disease (GvHD) have been reported following treatment with Lenti-D, and neither had there been any reports of graft failure or graft rejection.
“The results presented today [15 March] show that at 24 months of follow-up, 90% of patients in our pivotal study of eli-cel (ALD-102) were alive and free of MFDs,” said Richard Colvin, VP, head of severe genetic diseases clinical research and development, bluebird bio.
“As we continue the long-term follow-up of these patients, we are encouraged that there are now 14 boys who have reached at least their year five follow-up visit and continue to be living without MFDs, demonstrating the potential for a prolonged treatment effect,” he added.
In October 2020, the European Medicines Agency (EMA) accepted a marketing authorisation application (MAA) for Lenti-D in CALD.
