FDA Investigates Malignancy Risk Linked to Zolgensma Gene Therapy

Vector DNA integration was identified near or within the GLI1 oncogene in tumors from two treated patients

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The FDA is investigating malignancy risk after molecular testing linked two tumors to integration of Zolgensma vector DNA into patients’ genomes.
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The FDA received reports of tumors in the central and peripheral nervous systems, spinal and paraspinal regions, and kidney.
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Three cases involved abnormal GLI1 activity; the mechanism behind GLI1 overexpression in the third case remains under investigation.
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Novartis reported nine tumor cases among more than 6,000 Zolgensma-treated patients, with vector integration identified in two.
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The FDA said the risk also applies to Itvisma, reported no tumors after its use to date, and advised monitoring treated patients for tumors.