Bluebird Bio gene therapy sees encouraging early results in treatment of rare brain disease
- At the American Association of Neurology's annual meeting in Vancouver, BC, Bluebird Bio revealed promising, but very preliminary, clinical trial results for a gene therapy aimed at treating a rare and fatal neurological disease in young boys.
- In a small, ongoing study of 17 boys with cerebral adrenoleukodystrophy (CALD), none of the patients treated with Bluebird's Lenti-D gene therapy developed the major functional disabilities which are typical of the condition. The therapy also helped stabilize neurological function in all but one participant.
- Typically, CALD patients are treated with stem cell transplants from genetically matched donors. Bluebird's therapy, in contrast, uses transplantation with a patient's own stem cells, reducing the risk of graft versus host disease, and other complications.
Bluebird's study, known as Starbeam, still is a ways away from proving the effectiveness of its gene therapy. The data reported this week comes from a baseline of six months follow up with the 16 trial participants, eight of whom have between 12 and 24 months of follow up. Starbeam's primary objective is the proportion of patients with no major functional disabilities at 24 months post treatment, so a large portion of the participants still have not run the full course of the trial.
But the early results give some hope that Bluebird's therapy could prove an effective, and safer, alternative to allogeneic (donor-derived) stem cell transplantation. Not only did all patients remain free of major functional disabilities, but many also saw stabilization of neurological function with only one possible drug-related serious adverse event reported.
“CALD is a rare and deadly disease, and currently the only available treatment option is allogeneic hematopoietic stem cell transplant, which is often challenging for patients without a matched sibling donor,” said David A. Williams, the principal investigator of the Starbeam study and president of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. “It is exciting to see a potential autologous treatment option for these patients."
The disease is an inherited through a faulty X chromosome and causes progressive destruction of the protective sheath around nerve cells in the brain. It typically manifests itself in boys through learning and behavioral problems during childhood. If untreated, CALD leads to neurological function loss and eventual death.
Allogeneic stem cell transplantation, the only treatment option currently available, can be effective but risks graft-versus-host complications and requires a matched donor, usually a sibling. If Bluebird's Lenti-D can prove as effective a treatment option after two or more years post-treatment, the lower safety risks of the Lenti-D could prove compelling, notes Xconomy.
But given the need to demonstrate superior safety, the one serious adverse event and other adverse event reported merit attention. Five patients had re-emergence of gadolinium enhancement, a marker for CALD progression, at the 12-month mark, although two saw that issue resolved after 18 months.
Bluebird Bio is working on other gene therapies, including a treatment for transfusion-dependent ß-thalassemia, as well as several other T-cell cancer immunotherapies.
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