FDA Investigates Tumor Risk Linked to Novartis Gene Therapy Zolgensma

The U.S. Food and Drug Administration said on Friday it is investigating a risk of tumor formation linked to Zolgensma, Novartis's gene therapy used to treat young children with spinal muscular atrophy, after the drugmaker disclosed two cases in which tumors in children showed evidence of being connected to the treatment.

Novartis said it had received nine reports overall of tumors in patients previously treated with Zolgensma since the therapy was first approved in the United States in May 2019. In two of the cases, molecular analysis of tumor tissue showed that DNA from the therapy's viral vector had integrated into the patients' genomes within the GLI1 gene, which can promote cancer when activated, according to the FDA. The agency said it was also investigating a third tumor linked with GLI1.

The FDA said the reported tumors included malignancies of the central and peripheral nervous systems, the spinal and paraspinal regions, and the kidney. The agency described the cases as confirmed reports of product-related insertional oncogenesis, in which genetic material carried by the treatment inserts itself into a patient's DNA.

The finding matters because the current prescribing information for Zolgensma describes the risk of tumor formation from vector integration as only theoretical. The FDA said it is expeditiously evaluating whether the current prescribing information and Novartis's long-term follow-up studies are adequate to investigate and mitigate the risk, and whether regulatory action is appropriate.

The agency said the risk applies to both of Novartis's products that use the same vector and construct: Zolgensma, given by intravenous infusion to children under two years old, and Itvisma, given by injection into the spinal fluid to patients aged two and older. No cases of tumor formation have been reported following Itvisma treatment so far, the FDA said.

For now, the FDA said the overall benefits of both Zolgensma and Itvisma continue to outweigh their potential risks for their approved uses. Zolgensma is a one-time gene therapy for spinal muscular atrophy, a rare and serious muscle-wasting condition, and Novartis said it has been given to more than 6,000 children. The investigation does not amount to a conclusion that the treatment caused the reported tumors, and a reliable assessment of the risk is not yet possible.