The one-time therapy comes with a price tag of $3m and will become available at the end of this year through a limited number of Qualified Treatment Centers (QTCs) in the US, including Boston Children’s Hospital and Children’s Hospital of Philadelphia.
The approval of Skysona follows last month’s green light for Zynteglo, bluebird’s one-time gene therapy for beta thalassemia, marking two milestones for the company.
CALD is a rare, progressive, neurodegenerative disease that primarily affects young boys and causes irreversible neurologic decline, including major functional disabilities such as loss of communication, cortical blindness, requirement for tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement.
Nearly half of patients who do not receive treatment die within five years of symptom onset.
Up to now, treatments options have been limited to allogeneic hematopoietic stem cell transplant (allo-HSCT), which is associated with the risk of serious potential complications including death, that can increase dramatically in patients without a human leukocyte antigen (HLA) matched donor.
Although Skysona was approved in the EU last year, it was withdrawn shortly after as the company exited the region.
bluebird bio has been pinning its hopes on the US approvals of Zynteglo (granted last month) and Skysona, having warned that it was facing financial challenges along the long path to getting gene therapies to approval.
The Skysona Biologics License Application (BLA) was reviewed by the FDA under Priority Review, and consequently bluebird receives a rare pediatric priority review voucher upon approval.
SKYSONA was previously granted Orphan Drug designation, Rare Pediatric Disease designation, and Breakthrough Therapy designation.
As a condition of the Accelerated Approval, bluebird will provide confirmatory long-term clinical data to the FDA. bluebird anticipates that this will include data from the ongoing long-term follow-up study (LTF-304), which follows patients treated in clinical trials for 15 years, and from commercially treated patients.
CALD is a progressive and irreversible neurodegenerative disease that primarily affects young boys.
The disorder is caused by mutations in the ABCD1 gene that affect the production of adrenoleukodystrophy protein (ALDP) and subsequently leads to accumulation of very long-chain fatty acids (VLCFAs), primarily in the white matter of the brain and spinal cord. This accumulation leads to the breakdown of myelin, the protective sheath that nerve cells need to function effectively, especially for thinking and muscle control.
Skysona is a one-time gene therapy custom-designed to treat the underlying cause of CALD. It 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 stem cells (HSCs). The addition of the functional ABCD1 gene allows patients to produce the ALD protein (ALDP), which can then participate in the local degradation of very long-chain fatty acids (VLCFAs). This degradation of VLCFAs is believed to slow or possibly prevent further inflammation and demyelination.
FDA approval of Skysona was based on data from bluebird bio’s Phase 2/3 study ALD-102 (Starbeam) (N=32) and Phase 3 ALD-104 (N=35) study. All patients are encouraged to participate in a long-term follow-up study (LTF-304) to continue monitoring safety and efficacy over 15 years post treatment.
In August 2021 the FDA placed a clinical hold on the trial following a Suspected Unexpected Serious Adverse Reaction (SUSAR) of myelodysplastic syndrome (MDS). The hold was lifted in September 15 2022 prior to the completion of its review for the BLA.