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09.20.19

Gene Therapy for Cerebral Adrenoleukodystrophy Successful in Phase 2/3 Clinical Trial

  • KEYWORDS:
  • Cerebral adrenoleukodystrophy
  • Child neurology
  • Gene therapy

In a phase 2/3 study (NCT01896102) assessing efficacy and safety  of autologous CD34+ hematopoietic stem cell transplants genetically modified with a lentiviral vector encoding human adrenoleukodystrophy protein (ALDP) (Lenti-D; Bluebird Bio, Cambrige, MA), 32 boys less than age 17 years with cerebral adrenoleukodystropy (CALD) have been treated. Median follow-up time has been 21.2 months, and 15 children have completed the study and been enrolled in long-term follow-up. 

Of participants who have had 24 months of follow-up after 1-time treatment, 88% (15/17) are alive and free of major functional disabilities (MFD). Most children with CALD develop MFDs, including loss of ability to communicate, cortical blindness, need for tube feeding, total incontinence, wheelchair dependence, and complete loss of voluntary movement.

“With the longest follow-up from the phase 2/3 starbeam study now up to 5 years, the data show that all boys with CALD who were treated with Lenti-D and were free of MFDs at 24 months continued to be MFD-free,” said David Davidson, MD, chief medical officer, Bluebird Bio. “Importantly, there were no reports of graft failure or treatment-related mortality, and adverse events were generally consistent with myeloablative conditioning. These results support the potential of Lenti-D as a treatment for CALD, which we hope may become an option for the boys and their families affected by this devastating disease.”

Cerebral adrenoleukodystrophy (CALD) is an X-linked metabolic disorder affecting 1 in 21,000 male newborns globally and causes cognitive deficits and other MFD. Caused by ABCD1 mutations, CALD alters adrenoleukodystrophy protein (ALDP) production causing very long-chain fatty acid (VLCFAs) deposits primarily in white matter and adrenal cortex. 

Secondary and exploratory efficacy outcomes included changes in neurologic function score (NFS), resolution of gadolinium enhancement (GdE), and change in Loes score (an MRI measurement of white matter changes in CALD). Of the 32 patients treated, 30 had a stable NFS following treatment with Lenti-D, defined as NFS <4, without a change of >3 from baseline. 

No events of acute or chronic graft vs host disease have been reported after Lenti-D treatment and there have been no reports of graft failure, cases of insertional oncogenesis, or replication competent lentivirus. 

These results were announced at the 13th European Pediatric Neurology Society Congress in Athens, Greece.
 

Children with Spinal Muscular Atrophy Who Were Treated With Single-Dose Gene Therapy Continue Making Clinical Gains 

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