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FDA Advisory Committee Recommends Approval of Adrenoleukodystrophy Treatment
A US Food and Drug Administration (FDA) advisory panel unanimously recommended the approval of the investigational gene therapy elivaldogene autotemcel (eli-cel) for the treatment of early active cerebral adrenoleukodystrophy in pediatric patients without an available and willing human leukocyte antigen (HLA)-matched sibling hematopoietic stem cell donor.
The Cellular, Tissue, and Gene Therapies Advisory Committee voted 15-0 on June 9, 2022, that the benefits of eli-cel outweigh the risks.
Cerebral adrenoleukodystrophy is a rare, progressive neurodegenerative disease that primarily affects young boys and causes behavioral, cognitive, and neurological deficits, eli-cel developer Bluebird Bio explained in a news release. Without treatment, nearly half of patients die within 5 years of symptom onset. The only effective treatment at this time is allogeneic hematopoietic stem cell transplant (allo-HSCT). However, in patients without a matched sibling donor, allo-HSCT is linked with serious potential complications and mortality.
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The Biologics License Application for eli-cel is supported by efficacy and safety data from the phase 2/3 ALD-102 trial of 32 patients. Additionally, the application contains data for 35 participants from the phase 3 ALD-104 study. Patients treated with eli-cel were more likely to achieve both overall and event-free survival at 2 years than patients without a matched sibling donor, Bluebird Bio reported, with the clearest benefit for patients without a matched donor of any type.
In August 2021, the eli-cel clinical program was placed on clinical hold following a suspected, unexpected serious adverse reaction of myelodysplastic syndrome (MDS). Two additional cases have since been reported.
In its approval recommendation, the advisory committee advised the close monitoring of any patients treated with eli-cel for the development of MDS, MedPage Today reported.
“The FDA is concerned that with more time to follow subjects [from the ALD102 and ALD-104 trials], more will be diagnosed with cancer,” said Leah Crisafi, MD, an FDA clinical reviewer in the MedPage Today article.
“There are a number of subjects who are currently being closely watched due to concerns that they may be developing a hematologic malignancy,” Dr. Crisafi reportedly said. “And it is concerning that nearly all subjects who have received eli-cel have integration into the proto-oncogene MECOM, which is implicated in two of the three cancer cases diagnosed so far.”
The FDA is expected to respond to the Biologics License Application by September 16, 2022.
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