RARE Daily

European Regulators Give Bluebird Bio Positive Opinion for CALD Gene Therapy

May 21, 2021

The recommendation is for patients less than 18 years of age with early cerebral adrenoleukodystrophy (CALD) who have an ABCD1 genetic mutation and for whom a human leukocyte antigen (HLA)-matched sibling hematopoietic stem cell (HSC) donor is not available.

Photo: Richard Colvin, interim chief medical officer, Bluebird Bio

If approved by the European Commission, Skysona will be the first one-time gene therapy approved to treat CALD, a rare neurodegenerative disease that occurs in childhood and can lead to progressive, irreversible loss of neurological function and death.

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) and subsequently cause toxic accumulation of very long-chain fatty acids (VLCFAs), primarily in the adrenal gland and white matter of the brain and spinal cord. Approximately 40 percent of boys with ALD will develop CALD, the most severe form of ALD. CALD is a progressive and irreversible neurodegenerative disease that involves the breakdown of myelin, the protective sheath of the nerve cells in the brain responsible for thinking and muscle control. The onset of symptoms of CALD typically occurs in childhood (median age 7).

Skysona is a one-time investigational gene therapy that uses ex vivo transduction with the Lenti-D lentiviral vector (LVV) to add functional copies of the ABCD1 gene into a patient’s own hematopoietic (blood) stem cells (HSCs). The addition of the functional ABCD1 gene allows patients to produce the ALD protein, which is thought to facilitate the breakdown of VLCFAs. The goal of treatment with SKYSONA is to stabilize the progression of CALD and, consequently, preserve as much neurological function as possible, including the preservation of motor function and communication ability. Importantly, with Skysona, there is no need for donor HSCs from another person.

Skysona was accepted into the EMA’s Priority Medicines scheme (PRIME) in July 2018 and was previously granted Orphan Medicinal Product status. The U.S. Food and Drug Administration granted Skysona Orphan Drug status, Rare Pediatric Disease designation and Breakthrough Therapy designation for the treatment of CALD. Bluebird Bio is currently on track to submit the Biologics License Application in the United States by mid-2021.

The CHMP’s positive opinion will now be reviewed by the EC, which has the authority to grant marketing authorization for Skysona in the European Union. A CHMP positive opinion is one of the final steps before the EC decides whether to authorize a new medicine. A final decision by the EC for Skysona is anticipated in mid-2021.

“The goal of treatment with Skysona is to stabilize disease progression in children with CALD for whom a matched sibling donor is not available, in order to prevent further neurological decline and improve survival for these young patients,” said Richard Colvin, interim chief medical officer, Bluebird Bio. “This positive opinion from the CHMP marks the first regulatory approval recommendation for any gene therapy for CALD, bringing us closer to a one-time, durable treatment option that stabilizes neurological disease while reducing the risk of the serious immune complications associated with allogeneic stem cell transplantation (allo-HSCT), which is the only therapeutic option for children with this devastating disease.”

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