FDA Approves First Gene Therapy for Rare Neurodegenerative Disease

September 20, 2022

The Food and Drug Administration granted accelerated approval to elivaldogene autotemcel (eli-cel), marketed as Skysona (Bluebird Bio), to slow the progression of neurologic dysfunction in adolescent boys with early, active cerebral adrenoleukodystrophy (CALD).

Eli-cel is the first FDA-approved gene therapy for CALD, a rare, progressive, neurodegenerative disease caused by mutations in the ABCD1 gene that leads to irreversible neurologic decline, including major functional disabilities. According to Bluebird, the mortality rate for those who do not receive treatment within five years of symptom onset is almost 50%. The only other therapeutic option for CALD is hematopoietic stem cell transplantation.

FDA based the approval on data from Bluebird Bio’s Phase 2/3 study ALD-102 and Phase 3 ALD-104 study. Investigators assessed patients treated with eli-cel for neurologic function score (NFS) (with less than or equal to 1 indicating limited changes in neurologic function). They also monitored patients for the emergence of six major functional disabilities (MFDs) associated with CALD.

At 24 months from the time of first NFS greater than or equal to 1, patients treated with eli-cel had an estimated 72% likelihood of MFD-free survival, compared with an estimated 43% among untreated patients. Bluebird has now treated all patients in both studies, and a follow-up study that will monitor patients through 15 years post-treatment is underway.  

FDA approved eli-cel with a boxed warning for hematologic malignancy, including life-threatening cases of myelodysplastic syndrome, which has developed in patients treated with eli-cel in clinical studies. Additional considerations for prescribing clinicians are available from FDA.