FDA Investigates Cancer Risk in Novartis's Zolgensma Gene Therapy
The FDA is investigating postmarket reports of malignancies, including confirmed cases of product-related insertional oncogenesis, in patients treated with Novartis's gene therapy Zolgensma for spinal muscular atrophy, according to a Nov. 6 agency safety communication. Reports include tumors of the central and peripheral nervous systems, spinal and paraspinal regions, and kidney; three cases involved the GLI1 oncogene, and in two the therapy's viral vector DNA had integrated near or within that gene. The FDA determined the risk applies to both onasemnogene abeparvovec products, Zolgensma (IV infusion for children under 2) and Itvisma (intrathecal injection for patients 2 and older), since they share the same vector and construct, though no neoplasia cases have been reported after Itvisma. The agency said overall benefits still outweigh risks for approved uses but is evaluating whether the product label and Novartis's long-term follow-up studies are adequate.