CAMBRIDGE, Mass. – bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, today announced that interim data from the ongoing Phase 2/3 Starbeam Study (ALD-102) for the treatment of cerebral adrenoleukodystrophy (CALD) will be presented in an oral presentation during the Clinical Trials plenary session on April 20, 2016 at the American Academy of Neurology (AAN) 2016 Annual Meeting. The meeting is being held April 15 – 21, 2016 in Vancouver, BC, Canada.
“The childhood form of cerebral adrenoleukodystrophy is a devastating neurodegenerative genetic disease that affects boys and is generally fatal if left untreated. Allogeneic hematopoietic stem cell transplant (allo-HSCT) is currently the only available effective therapy, but is potentially associated with serious safety risks, including graft rejection, graft-versus-host disease and transplant-related mortality. The Lenti-D gene therapy product candidate consists of a patient’s own modified hematopoietic stem cells and should avoid the problems of immune-incompatibility that can complicate allo-HSCT,” said David Davidson, M.D., chief medical officer, bluebird bio. “We are excited to report interim data from the Starbeam Study of Lenti-D at this year’s AAN meeting. While these data are still early, we are encouraged by the safety profile and the radiographic and neurologic results reported in the abstract. We look forward to presenting updated data and additional findings in Vancouver next month.”
The Starbeam (ALD-102) Study
The Starbeam Study is assessing the efficacy and safety of an investigational gene therapy approach in boys up to 17 years of age with CALD. It involves transplantation with a patient’s own stem cells, which are modified to contain a functioning copy of the ABCD1 gene. The copy of the gene is intended to allow the body to produce ALDP, a protein critical for the breakdown of very long chain fatty acids (VLCFAs). Buildup of VLCFAs in the central nervous system contributes to neurodegeneration in CALD.
The primary efficacy endpoint for the Starbeam Study is the proportion of subjects with no major functional disabilities (MFDs) at 24 months post infusion. MFDs are six specific components of the Neurological Function Score (NFS) that would have a profound negative impact on patients’ lives: loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence and complete loss of voluntary movement.
Subjects enrolled in the study have:
- Eligibility for allo-HSCT but with no matched sibling donor
- Confirmed early-stage, active CALD as indicated by gadolinium enhancement on MRI (an indicator of active neuroinflammation)
- Loes score (a method for quantifying demyelination and atrophy on brain MRI in patients with ALD) between 0.5 – 9.0
- Neurological Function Score (NFS, a scoring system assessing clinical deficits with 15 functional domains) of one or less
- As of October 2015, 17 subjects with CALD have been treated with Lenti-D drug product with median follow-up time of nine months
- ALDP expression was observed in leukocytes of all subjects
- Reported adverse events were consistent with myeloablative conditioning. One serious adverse event with possible relation to drug product was reported (BK virus cystitis) and resolved with supportive care
- Integration site analyses have demonstrated polyclonal reconstitution in all subjects without evidence of clonal dominance
- In the 12 subjects with at least six months of follow-up:
- No major functional disabilities and no NFS worsening were reported
- The median change in Loes score was 1 (range 0-6)
- All subjects experienced resolution of gadolinium enhancement