Research & Development
Bluebird bio Receives EC Approval for Skysona Gene Therapy for Patients Less Than 18 Years of Age with Early Cerebral Adrenoleukodystrophy Without Matched Sibling Donor
22 July 2021 - - The European Commission has granted marketing authorization of Skysona (elivaldogene autotemcel, Lenti-D), a one-time gene therapy for the treatment of early cerebral adrenoleukodystrophy in patients less than 18 years of age with an ABCD1 genetic mutation, and for whom a human leukocyte antigen -matched sibling hematopoietic (blood) stem cell donor is not available, US-based gene and cell therapies developer bluebird bio, Inc. (NASDAQ: BLUE) said.

Skysona is the first one-time gene therapy approved in the European Union to treat CALD, a rare neurodegenerative disease that occurs in childhood and can rapidly lead to progressive, irreversible loss of neurologic function, and death.

Adrenoleukodystrophy 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 and subsequently causes 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% 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 that nerve cells need to function effectively, especially for thinking and muscle control. The onset of symptoms of CALD typically occurs in childhood (median age 7).

Early diagnosis of CALD is essential as the outcome of treatment varies with the clinical stage of the disease. Therefore, treatment must be administered before the disease progresses too far.

Skysona is a one-time gene therapy custom-designed to treat the underlying cause of the neurologic condition CALD.

Skysona uses ex vivo transduction with the Lenti-D lentiviral vector to add functional copies of the ABCD1 gene into a patient's own 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 expression of ALDP and effect of Skysona is expected to be life-long. The goal of treatment with SKYSONA is to stop 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.

Previously, the only therapeutic option available to CALD patients was transplantation of stem cells from a donor, called allogeneic hematopoietic stem cell transplant (allo-HSCT), which is associated with severe potential complications and mortality that increase in patients without a matched sibling donor.

It is estimated that more than 80% of patients diagnosed with CALD do not have an MSD.

Skysona was reviewed as part of the European Medicines Agency's Priority Medicines scheme (PRIME) and was previously granted Orphan Medicinal Product status. The marketing authorization is valid in all 27 member states of the EU, as well as Norway, Liechtenstein, and Iceland.

The marketing authorization of Skysona is supported by efficacy and safety data from the Phase 2/3 Starbeam study (ALD-102).

Additionally, the Phase 3 ALD-104 study (N=19; as of October 2020) is ongoing.

All patients who completed ALD-102, as well as those who will complete ALD-104, will be asked to participate in a long-term follow-up study (LTF-304).

The primary efficacy endpoint of the pivotal ALD-102 study was Major Functional Disabilities -free survival, measuring the proportion of patients who did not have any of the six MFDs, were alive, did not receive a second allo-HSCT or rescue cell administration, and had not withdrawn or been lost to follow-up at Month 24.

In ALD-102, 32 patients have been treated with Skysona and, as of October 2020, 30 of 32 patients were evaluable for follow-up at Month 24.

As of the data cutoff date, 90% (27/30) of the patients met the Month 24 MFD-free survival endpoint. As previously reported, two patients withdrew from the study at investigator discretion, and one experienced rapid disease progression early in the study, resulting in MFDs and subsequent death.

In ALD-102, 26 of 28 evaluable patients maintained a neurologic function score less than or equal to 1 through Month 24, and 24 of those patients had no change in their NFS, which showed maintenance of neurological function in the majority of patients.

All patients who completed ALD-102 enrolled for long-term follow-up in the LTF-304 study.

Skysona showed a durable effect on MFD-free survival, with most patients (26/27, 96.3%) that enrolled in LTF-304 remaining alive and maintaining their MFD-free status through their last follow-up on study, the company said.


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