– Additional follow-up data to be included in poster presentation at
– 15/17 (88%) of the patients infused with Lenti-D drug product remain alive and free of major functional disabilities (MFDs), the primary efficacy endpoint of the trial –
– No engraftment failure, graft versus host disease (GVHD) or life-threatening infections occurred; no evidence of insertional oncogenesis –
“I have seen firsthand the devastation that CALD can inflict on these
young boys and their families,” said
“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,” said Professor
The Starbeam Study is a global, multi-center study assessing the
efficacy and safety of an investigational gene therapy in boys up to 17
years of age with CALD. As of the
The primary efficacy endpoint for the Starbeam Study is the proportion of patients who are alive and have no major functional disabilities (MFDs) at 24 months post drug product infusion. MFDs are the six severe disabilities commonly attributed to CALD that, if present, 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. The primary safety endpoint is the proportion of patients who experience Grade 2+ acute GVHD or chronic GVHD at 24 months post-treatment. Secondary and exploratory assessments include Neurologic Function Score (NFS; a scoring system of 15 symptoms/signs across multiple domains used to evaluate the severity of gross neurologic dysfunction), gadolinium enhancement on MRI (an indicator of neuroinflammation), MRI Loes score (a method for quantifying brain lesions in patients with CALD using brain MRI), and additional safety assessments.
As of the
Additional secondary and exploratory endpoints as of the data cut-off include:
- 15/17 patients maintained NFS ≤ 1.
- Loes score has stabilized in 12/17 evaluable patients (71%). Stabilization is characterized as maintaining a Loes score ≤9 or not increasing a Loes score by ≥6 points.
- Gadolinium enhancement, positive in all patients at baseline, was negative in 16/17 patients by month 6. Diffuse gadolinium enhancement re-emerged in 6 patients at month 12. Subsequent fluctuations in gadolinium enhancement were observed, with 11/17 patients negative for gadolinium enhancement at their last follow-up. In all patients showing gadolinium re-emergence, the enhancement was less extensive compared to baseline. Initial results suggest that re-emergence of gadolinium enhancement does not correlate with clinical outcome.
Two patients did not meet the primary efficacy endpoint:
- Patient 2016 had not experienced an MFD, but withdrew from the study due to radiographic progression of disease and underwent allogeneic hematopoietic stem cell transplantation (HSCT). He subsequently died from complications of the allogeneic transplantation.
Patient 2018, as previously reported in
April 2016, had rapid disease progression beginning early in his participation in the study, resulting in multiple MFDs and an NFS of 15. The rapidity of his disease progression suggests it would have been difficult to alter his early neurological decline given that Lenti-D treatment takes months to exert a therapeutic effect in CALD.
“The founding of bluebird bio was based in large part on the potential
for Lenti-D to benefit boys with CALD,” said
CNS Presentation: Autologous hematopoietic stem cell gene therapy for cerebral adrenoleukodystrophy – Interim results and initial long-term follow-up of an international clinical study (Poster #133)
An update of the Starbeam study data will be presented at the CNS Annual
Meeting. As of
- The final patient in the initial cohort of 17 patients has achieved 24 months of post-treatment follow-up
- 15 of the first 17 patients (88%) (95% CI: 64% to 99%) infused with Lenti-D drug product remain alive and free of major functional disabilities (MFDs), the primary efficacy endpoint of the trial
- An additional 4 patients have been infused with Lenti-D drug product with a median drug product vector copy number (VCN) of 1.4 (range 1.2-1.9)
- The safety profile in 21 treated patients remains consistent with the previously reported safety profile
Secondary and exploratory outcome measures in the initial cohort of 17
patients were generally consistent with data as reported in the
publication in the
New England Journal of Medicine:
- 15/17 patients maintained NFS ≤ 1 at 24 months. Loes score is stable at 24 months in 12/17 patients defined as maintaining a Loes score of ≤ 9 or not increasing by ≥ 6 from baseline.
- 14/17 patients negative for gadolinium enhancement at their last follow-up
About the Starbeam (ALD-102) Study
The Starbeam Study is assessing the efficacy and safety of an investigational gene therapy 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 functional copies of the ABCD1 gene. This gene addition should result in the production of functional adrenoleukodystrophy protein (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.
Subjects enrolled in the study:
- Are eligible for allogeneic HSCT but with no matched sibling donor
Have confirmed early-stage, active CALD as indicated by:
- Gadolinium enhancement on MRI
- Loes score between 0.5 and 9.0
- NFS of one or less
Patients in the Starbeam study have been treated at Boston Children’s
Also known as Lorenzo’s Oil disease, adrenoleukodystrophy (ALD) is estimated to affect one in every 21,000 male births worldwide. The cerebral form of the disease, cerebral adrenoleukodystrophy (CALD), is a potentially fatal form of ALD. CALD involves a breakdown of the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control.
Currently, the only effective treatment option for patients with CALD is allogeneic hematopoietic stem cell transplant (HSCT). Potential complications of allogeneic HSCT, which can be fatal, include graft failure, graft versus host disease (GVHD) and opportunistic infections, particularly in patients who undergo allogeneic HSCT using cells from a donor who is not a matched, unaffected sibling.
Early diagnosis of CALD is important, as the outcome of HSCT varies with
clinical stage of the disease at the time of transplant. Favorable
outcomes have been observed in patients who undergo transplant in the
early stages of cerebral disease. Newborn screening for ALD is a
critical enabler of early diagnosis and successful treatment of ALD. In
About bluebird bio, Inc.
With its lentiviral-based gene therapies, T cell immunotherapy expertise and gene editing capabilities, bluebird bio has built an integrated product platform with broad potential application to severe genetic diseases and cancer. bluebird bio’s gene therapy clinical programs include its Lenti-D™ product candidate, currently in a Phase 2/3 study, called the Starbeam Study, for the treatment of cerebral adrenoleukodystrophy, and its LentiGlobin® BB305 product candidate, currently in three clinical studies for the treatment of transfusion-dependent β-thalassemia, also known as β-thalassemia major, and severe sickle cell disease. bluebird bio’s oncology pipeline is built upon the company’s leadership in lentiviral gene delivery and T cell engineering, with a focus on developing novel T cell-based immunotherapies, including chimeric antigen receptor (CAR T) and T cell receptor (TCR) therapies. bluebird bio’s lead oncology programs, bb2121 and bb21217, are anti-BCMA CAR T programs partnered with
bluebird bio has operations in
LentiGlobin and Lenti-D are trademarks of bluebird bio, Inc.
This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the clinical and market potential of the Company’s Lenti-D product candidate. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the preliminary efficacy and safety data for our Lenti-D product candidate from the Starbeam Study will not continue or persist, the risk of cessation or delay of any of the ongoing clinical studies and/or our development of Lenti-D, the risks regarding future potential regulatory approvals of Lenti-D, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the
Source: bluebird bio, Inc.
bluebird bio, Inc.
Investors & Media:
Elizabeth Pingpank, 617-914-8736