The U.S. Food and Drug Administration (FDA) has granted accelerated approval for elivaldogene autotemcel (el-cel) to treat males 4-17 years of age with early, active 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 die within five years of symptom onset.
The accelerated approval was granted based on the results from the Phase 2/3 study ALD-102 and the Phase 3 ALD-104 study. Both open-label, single-arm studies enrolled boys with early, active CALD who had elevated very long chain fatty acid (VLCFA) values, a Loes score between 0.5 and 9 (inclusive), and gadolinium enhancement on magnetic resonance imaging (MRI) of demyelinating lesions. Additionally, patients were required to have a neurologic function score (NFS) of ≤ 1, indicating limited changes in neurologic function. The efficacy of the gene therapy was compared to a natural history population.
The studies observed MFD-free survival from onset of symptoms (NFS ≥ 1) in el-cid treated patients (N=11) was 72% compared to 43% in untreated patients (N=7).
As a condition of the Accelerated Approval, bluebird bio must provide confirmatory long-term clinical data to the FDA.
In a news release, bluebird bio noted that the gene therapy will have a wholesale acquisition cost of $3.0 million. The gene therapy will likely be available later this year in a limited number of Qualified Treatment Centers (QTCs) in the United States, including Boston Children’s Hospital and Children’s Hospital of Philadelphia.
The therapy comes with a Boxed Warning for hematologic malignancy. Boys have been diagnosed hematologic malignancies after el-cid administration, and the cancers appear to be the result of the el-cid lentiviral vector, Lenti-D, integrating in proto-oncogenes. Monitor patients closely for evidence of malignancy through complete blood counts at least every 6 months and through assessments for evidence for clonal expansion or predominance at least twice in the first year and annually thereafter; consider bone marrow evaluations as clinically indicated.
Last year, we talked with Richard Colvin, MD, PhD, Vice President of Clinical Development and Interim Chief Medical Officer at Bluebird Bio, about the gene therapy and the transformative impact it has had for CALD patients.
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