After good news in sickle cell, bluebird bio follows up with positive long-term data in Lorenzo’s Oil disease
Less than a week after bluebird bio said their sickle cell gene therapy was “very unlikely” to have caused a case of acute myeloid leukemia, the company is presenting some more good news for a different program.
Revealing long-term data in the rare genetic disorder cerebral adrenoleukodystrophy (CALD), bluebird said Monday that 27 of 30 evaluable patients in a pivotal Phase II/III study were alive and free of major functional disabilities at the two-year mark. And they’re also highlighting data from a follow-up study where 14 patients remain unaffected by such disabilities through five years.
Bluebird is hoping to provide an alternative to allogeneic stem cell transplants, which is the current standard of care for CALD, also known as Lorenzo’s Oil disease, the company’s head of rare genetic disease R&D Richard Colvin said in a statement. The five-year data have especially “encouraged” the team that the therapy, dubbed Lenti-D, can have a safe and prolonged treatment effect.
Data come from a total of 32 patients, with a median follow-up of 38.6 months. The follow-ups ranged from 13.4 to 82.7 months, and in addition to the 14 who reached five years since treatment, seven of those individuals have hit the six-year milestone.
Two patients dropped out at investigator discretion, as bluebird has previously said. A third patient also — bluebird reported several years ago — experienced rapid progression of the disease early on in treatment and ultimately died.
Another two additional patients have not yet reached the slated two-year timeframe, and neither have shown any evidence of major functional disabilities.
CALD is the most severe form of adrenoleukodystrophy; it’s a rare, X-linked metabolic disorder that affects about one in 21,000 male newborns around the world, bluebird says. Mutations in the ABCD1 result in toxic buildup of very long-chain fatty acids, usually in the parts of the brain and spinal cord.
The disease is associated with six major functional disabilities that bluebird is looking to stamp out with its treatment. These include the loss of communication, cortical blindness, the need for tube feeding, incontinence, wheelchair dependence and the loss of all voluntary movement.
Bluebird is also evaluating Lenti-D in a separate Phase III trial, looking at CALD patients after they’ve received busulfan and fludarabine conditioning. Researchers have treated 19 patients with a median follow-up of 8.6 months, and 17 of those 19 have achieved neutrophil engraftment. Fifteen of 19 also had platelet engraftment as of the November data cutoff date.
Since this study doesn’t yet have any patients who have reached the 24-month mark, bluebird’s not releasing any efficacy data from this trial just yet. All reported data from the Phase II/III and parallel Phase III studies are current as of October 2020, bluebird said.
The Cambridge, MA-based biotech has been plagued by setbacks and safety issues over the last year, with two serious adverse events popping up in the sickle cell program last month triggering a fresh round of concerns over its lentivirus delivery platform. But last week’s news proved a momentary sigh of relief as researchers continue to look into a second event, thought to be myelodysplastic syndrome.
With the Lenti-D data being presented at a scientific forum Monday, bluebird remains on track to submit its BLA pitch to the FDA in “mid-2021.”