Bluebird Bio has claimed an FDA breakthrough designation for its Lenti-D gene therapy for cerebral adrenoleukodystrophy (CALD) – a rare neurological disease mainly affecting young males.
The new status – which could result in a speedy review by the US regulator and shorten the time to market for the therapy – comes after impressive data from a phase II/III trial suggesting it could stabilise disease for more than two years in boys with the highly progressive and life-threatening disorder.
Data from 17 patients in the STARBEAM study was published in the New England Journal of Medicine last October, and showed that Lenti-D (elivaldogene tavalentivec) stabilised disease in 15 of them, with one boy dying as a result of the disease and another progressing despite therapy.
CALD – also known as Lorenzo’s Oil disease – is caused by progressive destruction of the myelin sheath that surrounds nerves responsible for thinking and muscle control, resulting in a relentless deterioration that typically leads to a vegetative state or death within a few years of diagnosis. Most patients die before the age of 10.
Lenti-D tries to interrupt that process by replacing a mutated gene in CALD patients with a functional gene. A viral vector is used to insert the new sequence into haematopoietic stem cells harvested from the patent, which are then given back and have the potential to develop into multiple cell types that can produce a functional version of the ALD protein that is lacking in CALD.
Bluebird’s gene therapy approach could do away with the need for stem cell transplants in CALD patients. This is currently the only treatment for the disease but carries a significant risk from the high-dose chemotherapy used to prepare patients for the procedure and other potential complications such as graft-versus-host disease, when the transplanted cells recognise the recipient’s cells as ’foreign’ and attack them.
The STARBEAM trial enrolled patients without matched donors, who are particularly unlikely to have a good outcome after a stem cell transplant.
“The founding of bluebird was inspired by the potential to develop a one-time gene therapy for boys suffering from this potentially fatal form of adrenoleukodystrophy,” said Bluebird’s chief medical officer David Davidson.
The breakthrough designation “brings us one step closer to realising this mission to bring new hope to the patients and families affected by this devastating disease”, he added.
Lenti-D is Bluebird’s lead gene therapy programme, after its sickle cell disease candidate LentiGlobin missed the mark in a clinical trial in 2015 because of varying responses to treatment, forcing the company to revamp its manufacturing process.
The company has also made significant progress in the interim with its Celgene-partnered CAR-T cancer immunotherapy programme, reporting dramatic responses with its multiple myeloma candidate bb2121 last December.