On July 21, 2021, bluebird bio announced that the European Commission (EC) has granted it a single-dose gene therapy Skysona (elivaldogene autotemcel, also known as Lenti-D) marketing license for the treatment of patients under the age of 18 with mutations in the ABCD1 gene Patients with early cerebral adrenoleukodystrophy (CALD). These patients cannot obtain matching donors for hematopoietic stem cell (HSC) transplantation.

The news pointed out that Skysona is the first gene therapy approved by the European Union (EU) for the treatment of CALD. Previous trials have proved that Skysona has a long-lasting effect in improving patient survival outcomes and preserving neurological function, with the longest follow-up time of nearly 7 years (82.7 months).

This approval is based on the results of the pivotal Phase 2/3 ALD-102 trial. The primary efficacy endpoint of the trial is MFD-free survival. 90% (n=27/30) of patients reached the MFD-free survival endpoint at the 24th month, and the neurological function of most patients was maintained. In addition, its phase 3 ALD-104 trial is also underway. All patients who complete ALD-102 and those who complete ALD-104 in the future will be enrolled in a long-term follow-up study called LTF-304.

During long-term follow-up, Skysona showed a lasting effect on MFD-free survival. Most patients (n=26/27, 96.3%) survived and remained MFD-free during the last follow-up of the study. The median follow-up time was 3.2 years (38.6 months, 13.4-82.7 months).

In terms of safety, adverse reactions observed in clinical trials include viral cystitis, pancytopenia and vomiting. To date, there have been no reports of graft-versus-host disease (GVHD), graft failure or rejection, or transplant-related deaths (n=51). Although no lentiviral vector-mediated tumorigenesis related to Skysona (including myelodysplasia, leukemia or lymphoma) has been reported, there is a potential risk of malignant tumors after Skysona treatment.

bluebird bio is currently planning to submit a Biologics License Application (BLA) to the FDA in mid-2021.

Mr. Andrew Obenshain, president of bluebird bio for serious genetic diseases, said: “One of the missions of bluebird bio when it was founded was to develop a method to treat CALD at the gene level. Skysona is the first single-dose gene therapy approved by the EU for CALD patients. The approval represents an important milestone in our more than two decades of research and development work."