RESEARCH TRIANGLE PARK – bluebird bio, a global gene therapy company with a new manufacturing facility in Durham, has unveiled positive results in clinical trials of its treatment for boys with a rare and deadly neurological disorder.

The company is developing the gene therapy, elivaldogene autotemcel (eli-cel, branded as Lenti-D), to treat boys suffering from cerebral adrenoleukodystrophy (CALD). It’s a hereditary disease that involves a breakdown of the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control.

bluebird bio’s Durham facility. — bluebird bio photo

bluebird presented the updated results at the 46th Annual Meeting of the European Society for Blood and Marrow Transplantation, taking place virtually through Sept. 1.

Adrenoleukodystrophy (ALD) is a rare, X-linked metabolic disorder that is estimated to affect one in 21,000 male newborns worldwide. Approximately 40% of boys with ALD will develop CALD, the most severe form of the genetic disease. CALD is a progressive neurodegenerative disease that involves breakdown of myelin, the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control.

Symptoms of CALD usually occur in early childhood and progress rapidly, if untreated, leading to severe loss of neurologic function, and eventual death, in most patients. It typically results in loss of communication, blindness, a need for tube feeding, total incontinence, wheelchair dependence, and complete loss of voluntary movement. Nearly half of boys with CALD who do not receive treatment will die within five years of symptom onset.

David Davidson, M.D., chief medical officer at bluebird, said the only treatment currently available is allogeneic hematopoietic stem cell transplantation (allo-HSCT), using cells donated from another person. That comes with associated, significant risks, he noted, including transplant-related mortality, graft failure or rejection, and graft-versus-host disease (GVHD).

87% survival without major functional disabilities

Davidson said a solid majority of the boys involved in bluebird’s trial, called Starbeam, have responded well to the Lenti-D treatment.

“Eighty-seven percent of patients in our Phase 2/3 Starbeam study of eli-cel are alive and free of major functional disabilities (MFDs) at 24 months or more of follow-up, he reported. “Importantly, there were no reports of graft failure, graft rejection, or GVHD. It is gratifying to see the consistent outcomes with eli-cel and the durability of the treatment effect demonstrated in the children participating in our long-term follow-up study – including 10 boys who have now reached at least their Year 5 follow-up visit.”

bluebird bio exterior
bluebird bio’s Durham facility. — bluebird bio photo

Another scientist involved in the Starbeam study who reported results at the annual meeting is Jörn-Sven Kühl, of the Department of Pediatric Oncology, Hematology and Hemostaseology in the University Hospital Leipzig’s Center for Women’s and Children’s Medicine.

“Patients with CALD experience a rapid decrease in neurologic function after the initial onset of clinical symptoms, so early diagnosis and treatment is critical in order to stop the disease progression and preserve their neurological function,” said Kühl. “In the Phase 2/3 Starbeam study, 31 of 32 patients had a stable neurologic function score, suggesting that disease progression had stabilized and minimal neurological function was lost, following eli-cel infusion. These results … are very encouraging and suggest treatment with eli-cel may prevent neurological decline in boys with CALD.”

Eli-cel is a one-time investigational gene therapy designed to address the underlying genetic cause of CALD by adding functional copies of the targeted gene into a patient’s own blood stem cells. The company corrects the cellular abnormality in a lab procedure by introducing the genetic fix using the Lenti-D lentiviral vector (LVV).

That addition of a functional gene allows patients to produce the normal protein needed to break down the toxins in the brains of CALD sufferers.

Patients who complete the Starbeam trial subsequently enroll in a long-term follow-up study to monitor their progress.

(C) N.C. Biotech Center