Richard Colvin, MD, PhD, Vice President of Clinical Development and Interim Chief Medical Officer at Bluebird Bio, discusses the recent announcement by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) that they have adopted a positive opinion recommending marketing authorization for Skysona (elivaldogene autotemcel, Lenti-D™), a one-time gene therapy for the treatment of early cerebral adrenoleukodystrophy (CALD).
CALD is a progressive neurodegenerative disease that involves the breakdown of myelin. Symptoms of CALD usually occur in early childhood and, if untreated, rapidly leads to severe loss of neurologic function and eventual death in most patients. CALD is associated with six major functional disabilities (MFDs), which severely compromise a patient’s ability to function independently: loss of communication, cortical blindness, need for tube feeding, total incontinence, wheelchair dependence, and complete loss of voluntary movement. Nearly half of boys with CALD who do not receive treatment will die within five years of symptom onset.
The positive CHMP opinion is supported by positive efficacy and safety data from the Phase 2/3 Starbeam study (ALD-102). The primary efficacy endpoint of the pivotal ALD-102 study was 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not have any of the six MFDs, were alive, did not receive a second allo-HSCT or rescue cell administration, and had not withdrawn or been lost to follow-up at Month 24. As Dr. Colvin states, to date, 32 patients have been treated with elivaldogene autotemcel in ALD-102. Ninety percent of the patients met the Month 24 MFD-free survival endpoint. Two patients withdrew from the study at investigator discretion, and one experienced rapid disease progression early on in the study, resulting in MFDs and subsequent death.
Additional efficacy data from the ALD-102 study showed that 26 of the 28 evaluable patients maintained a neurologic function score (NFS) less than or equal to one 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. The treatment regimen, comprising mobilization/apheresis, conditioning and elivaldogene autotemcel infusion, had a safety/tolerability profile primarily reflective of the known effects of mobilization/apheresis and conditioning.
To learn more about CALD and other rare neurological disorders, visit checkrare.com/diseases/neurology-nervous-system-diseases/
