Bluebird bio’s stem cell-gene therapy offers hope for CALD patients

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Interim results from bluebird bio’s Phase 2/3 study demonstrate the safety and efficacy of hematopoietic stem cells transduced with Lenti-D lentiviral vector for treating early-stage cerebral adrenoleukodystrophy (CALD).

X-linked adrenoleukodystrophy, also known as Lorenzo’s Oil disease, is caused by mutations in the ABCD1 gene that encodes a protein of the peroxisomal membrane named ALDP. It affects one in every 21,000 male births worldwide. The cerebral form of the disease, CALD is characterized by demyelination and neurodegeneration and is fatal. Allogeneic hematopoietic stem cell transplantation is the only effective treatment option available currently, but it carries significant risk.

In the study published in The New England Journal of Medicine, Eichler et al. report interim results of bluebird bio’s Phase 2/3 STARBEAM trial. The study evaluated the safety and efficacy of transplantation with autologous CD34+ hematopoietic stem cells transduced with Lenti-D (lentiviral vector that encoded ABCD1 gene) for the treatment of cerebral adrenoleukodystrophy in children. The primary end point of the study was being alive and having no major functional disability at 24 months after infusion. The study assessed the occurrence of graft-versus-host disease, death and major functional disabilities, as well as changes in neurologic function.

17 boys were included in the study and received the Lenti-D Drug Product intravenously following myeloablative conditioning. The interim analysis was performed at the median follow-up was 29.4 months. 15 out of 17 patients were alive at the end of 24 months, with no graft failure and no major functional disabilities. Out of the remaining 2, one died from disease progression and the other one was withdrawn from the study and died from complications of a subsequent allogeneic transplantation.

Positive results obtained from the 15 patients suggest that Lenti-D gene therapy may be a safe and effective alternative to allogeneic stem-cell transplantation in boys with early-stage cerebral adrenoleukodystrophy. However, additional follow-up is needed to fully assess the duration of response and long-term safety of the treatment.

Prof. Adrian Thrasher at UCL’s Great Ormond Street Institute of Child Health and co-investigator of the study commented: “This data we are seeing from this study of gene therapy is a really exciting development for boys with CALD. Not only does the data show that Lenti-D has the potential to minimise further progression of this devastating disease, but the technique also avoids the need for a matched bone marrow donor, which can be difficult to find and can delay vital treatment. The results from this trial thus far are very encouraging and will pave the way for further development of state-of-the-art treatments for children with life-limiting conditions.”

Source: Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy. Eichler F et al., The New England Journal of Medicine, October 2017. DOI