Benzinga | Mar 15, 2021 05:40AM EDT

bluebird bio Announced Long-Term Data for elivaldogene autotemcel (eli-cel, Lenti-D) Gene Therapy for Cerebral Adrenoleukodystrophy (CALD) Show 90% of Evaluable Patients (27/30) Alive and Free of Major Functional Disabilities at Two Years Follow-up in Phase 2/3 Starbeam Study

bluebird bio, Inc. (NASDAQ:BLUE) announced new data from the clinical development program for its investigational elivaldogene autotemcel (eli-cel, Lenti-D™) gene therapy in patients with cerebral adrenoleukodystrophy (CALD), including updated results from the pivotal Phase 2/3 Starbeam study (ALD-102) and the long-term follow-up study LTF-304, as well as safety outcomes from the Phase 3 ALD-104 study. Data were presented today in an oral presentation during the Presidential Symposium at the 47th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT 2021), taking place virtually from March 14 - 17, 2021.

"The progression of CALD may occur rapidly, leading to severe neurological decline, and often death, of boys with this disease if untreated. The results presented today show that at 24 months of follow-up, 90% of patients (27/30) in our pivotal study of eli-cel (ALD-102) were alive and free of major functional disabilities (MFDs). As we continue the long-term follow-up of these patients, we are encouraged that there are now 14 boys who have reached at least their Year 5 follow-up visit and continue to be living without MFDs, demonstrating the potential for a prolonged treatment effect," said Richard Colvin, M.D., Ph.D., VP, head of severe genetic diseases clinical research and development, bluebird bio. "There is a great need for alternative treatment options that reduce the risk of the serious immune complications associated with allogeneic stem cell transplantation, the current standard of care for CALD. Today's presentation continues to illustrate the potential of eli-cel as a one-time, durable treatment option for this devastating disease."

Adrenoleukodystrophy (ALD) is a rare, X-linked metabolic disorder that is estimated to affect one in 21,000 male newborns worldwide. ALD is caused by mutations in the ABCD1 gene that affect the production of adrenoleukodystrophy protein (ALDP) and subsequently cause toxic accumulation of very long-chain fatty acids (VLCFAs) primarily in the adrenal cortex and white matter of the brain and spinal cord.

Approximately 40% of boys with adrenoleukodystrophy will develop CALD, the most severe form of ALD, which is progressive and neurodegenerative, involving the breakdown of the nerve cells in the brain that are responsible for thinking and muscle control. CALD is associated with six MFDs, which severely compromise a patient's ability to function independently: loss of communication, cortical blindness, need for tube feeding, total incontinence, wheelchair dependence, and complete loss of voluntary movement. CALD usually occurs in early childhood and progresses rapidly, if untreated, leading to severe loss of neurologic function, and eventual death, in most patients.

Eli-cel is a one-time investigational gene therapy designed to add functional copies of the ABCD1 gene into a patient's own hematopoietic (blood) stem cells (HSCs) that have been transduced ex vivo with the Lenti-D lentiviral vector (LVV). The addition of the functional ABCD1 gene allows patients to produce the adrenoleukodystrophy protein (ALDP), which is thought to activate the breakdown of VLCFAs. The goal of treatment with eli-cel is to stabilize the progression of CALD and consequently preserve as much neurological function as possible. Importantly, with eli-cel, there is no need for donor HSCs from another person.

"CALD is a terrible disease that occurs in early childhood and, if left untreated, often leads to eventual death for these boys, a difficult fact for any clinician to bear. These data from the Phase 2/3 Starbeam study show some potentially promising evidence, with up to almost seven years of follow-up and nearly all patients have a stable neurologic function score (n=31/32), indicating that minimal neurologic function was lost following eli-cel infusion. In addition there were no reports of graft failure, graftrejection, or graft-versus-host disease," said Dr. Jrn-Sven Khl, Department of Pediatric Oncology, Hematology and Hemostaseology, Center for Women's and Children's Medicine, University Hospital Leipzig. "These long-term results therefore suggest treatment with eli-cel may stabilize disease progression and consequently preserve as much neurological function as possible in boys with CALD."