Capsule with DNA inside
Tablets with genetic code inside. Concept of the advancement of medicine in the treatment of diseases.

A U.S. FDA advisory committee unanimously approved bluebird bio’s elivaldogene autotemcel (eli-cel) gene therapy for early active cerebral adrenoleukodystrophy (CALD) in certain patients. The committee’s recommendation is based on the Biologics License Application (BLA) currently under priority review by the FDA with a PDUFA goal date set for September 16, 2022.

“For decades, the CALD community has fought for the opportunity to stave off the rapid, irreversible decline associated with this devastating disease,” said Andrew Obenshain, chief executive officer, bluebird bio. “Today we are one step closer to delivering a potentially lifesaving therapy for CALD.”

The nod came from the US Food and Drug Administration’s (FDA) Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC). On the question “Do the benefits of eli-cel outweigh the risks, for the treatment of any sub-population of children with early active cerebral adrenoleukodystrophy (CALD)?” the CTGTAC voted 15 (yes) to 0 (no), bluebird reported in a press release.

CALD is a rare, progressive, neurodegenerative disease that primarily affects young boys and causes behavioral, cognitive, and neurological deficits. Nearly half of patients who do not receive treatment die within five years of symptom onset.

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is currently the only effective treatment option but is associated with serious potential complications and mortality that increase in patients without a matched sibling donor. If approved, eli-cel will be the first gene therapy approved to address the underlying genetic cause of CALD—offering the more than 70% of U.S. patients diagnosed with CALD an alternative to allo-HSCT.

bluebird is seeking approval for the treatment of early CALD in patients less than 18 years of age who do not have an available and willing human leukocyte antigen (HLA)-matched sibling hematopoietic stem cell donor.

The eli-cel clinical program was placed on a clinical hold following a Suspected Unexpected Serious Adverse Reaction (SUSAR) of myelodysplastic syndrome (MDS) in August 2021. Two additional cases of MDS have subsequently been reported. The company reports that “All patients who received eli-cel in the clinical program continue to be closely monitored, per study protocols.”

The CTGTAC also discussed the overall safety of lentiviral vector (LVV) gene therapies, concluding in a 13 to 1 vote that the safety data from lovo-cel for sickle cell disease is not relevant to the review of eli-cel.

In addition to granting eli-cel BLA priority review, the FDA previously granted eli-cel Orphan Drug status, Rare Pediatric Disease designation, and Breakthrough Therapy designation. bluebird bio is eligible to receive a priority review voucher upon potential approval of eli-cel.

Adrenoleukodystrophy (ALD) is a rare, X-linked metabolic disorder that primarily affects males; worldwide, an estimated one in 21,000 male newborns are diagnosed with ALD. The disorder is caused by mutations in the ABCD1 gene that affect the production of adrenoleukodystrophy protein (ALDP). Approximately 40% of boys with ALD will develop CALD, a progressive and irreversible neurodegenerative disease that involves the breakdown of myelin, the protective sheath that nerve cells need to function effectively, especially for thinking and muscle control.

eli-cel uses ex vivo transduction via LVV to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells. Bluebird also has research programs for sickle cell disease and beta-thalassemia.

Also of Interest