- While the study is small, interim data from the Starbeam Phase 2/3 trial of bluebird bio's Lenti-D has shown a flutter of hope for patients with cerebral adrenoleukodystrophy (CALD), a fatal disease also known as Lorenzo's Oil disease.
- Published in the New England Journal of Medicine, the study results showed bluebird bio's hematopoietic stem-cell gene therapy met the primary endpoint, with 15 of the 17 patients (or 88%) receiving the therapy free of major functional disabilities (MFD) 24 months after treatment. Median follow-up at the time of data analysis was 29.4 months. This is higher than the pre-defined efficacy success benchmark of 76% MFD-free survival at 24 months.
- One of the two remaining patients withdrew because of disease progression, and the other had not reached 24 month follow up at the data cutoff. Most of the adverse events were linked with the chemotherapy needed pre-transplant. There was one Grade 3 case of hemorrhagic cystitis that has since been resolved but may be linked with the treatment.
Correction: A previous version of this article incorrectly described the phase of the SUNBEAM trial.
This is early news on a small study in a rare disease, but — in addition to providing hope for a debilitating, disabling and sometimes fatal disease — it provides validation for the technology behind bluebird bio's lead therapeutic, Lenti-D.
The study is ongoing, and as of Aug. 25, 15 of the 17 remain alive and free of MFDs. These are the six severe disabilities linked with CALD that can have a negative impact on patients’ lives: loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence and complete loss of voluntary movement.
The 16th patient had disease that progressed early and rapidly, ending up with multiple MFDs. "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," bluebird said in an Oct. 4 statement.
"The founding of bluebird bio was based in large part on the potential for Lenti-D to benefit boys with CALD," bluebird's Chief Medical Officer David Davidson said. "It is encouraging to see patients doing clinically well more than three years following treatment for this rare and devastating disease, and we are excited to have achieved excellent Lenti-D drug product vector copy numbers for the first four patients treated in the expansion cohort."
Cerebral adrenoleukodystrophy (CALD) is a potentially fatal form of adrenoleukodystrophy (ALD), an X-linked genetic disorder sometimes known as Lorenzo's Oil disease. ALD affects just one in 21,000 male births worldwide, and destroys the protective myelin sheath around the neurons in the brain. It leads to deafness, blindness, seizures, loss of muscle control and dementia, resulting in permanent disability or death. The only current effective treatment is allogeneic hematopoietic stem cell transplant (HSCT).
bluebird bio had a shares boost at the end of September, with an 11% jump on the news of the first patient to be treated with the company's CAR-T therapy, bb21217, for the treatment of relapsed/refractory multiple myeloma. The share price has fallen by a similar amount since then, despite the Lenti-D news.