Rare Daily Staff

The U.S. Food and Drug Administration placed a clinical hold on Bluebird Bio’s experiment gene therapy eli-cel for cerebral adrenoleukodystrophy follow a report of a suspected unexpected serious adverse reaction of myelodyplastic syndrome in a patient treated with the product more than a year ago in a phase 3 study.

News of the halt sent shares of Bluebird down more than 25 percent to $18.58 in intraday trading.

The company said evidence currently available suggests that specific design features of Lenti-D LVV, the vector used for its gene therapy, likely contributed to this event. The company has shared this information with the independent data monitoring committee of the study and the FDA has placed the program on a clinical hold.

The company said it does not anticipate the clinical hold to impact its programs in sickle cell disease (SCD), β-thalassemia or oncology. Subject to resolution of the clinical hold, the company anticipates completing the submission of the rolling BLA for eli-cel in 2021.

“Our hearts go out to this patient and his family, who are dealing with a challenging diagnosis,” said Nick Leschly, chief executive of Bluebird Bio. “Given what we know, we remain confident that eli-cel can offer hope for patients and families impacted by this devastating disease who have very few treatment options. We are committed to working with regulators and physicians in order to resolve this hold as soon as possible and bring this important therapy to patients in need.”

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 and subsequently cause toxic accumulation of very long-chain fatty acids primarily in the adrenal cortex and white matter of the brain and spinal cord.

Approximately 40 percent of boys with adrenoleukodystrophy will develop CALD, the most severe form of ALD. 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. Nearly half of boys with CALD who do not receive treatment will die within five years of symptom onset.

Eli-cel is a one-time investigational gene therapy designed to address the underlying genetic cause of CALD by adding functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells that have been transduced ex vivo with the Lenti-D lentiviral vector. The addition of a functional gene allows patients to produce the adrenoleukodystrophy protein, which is thought to break down the toxic accumulation of very long-chain fatty acids in the brain. There is no need for donor hematopoietic stem cells from another person, as is required for allogenic transplantation.

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