FDA Probes Tumour Risk Linked to Novartis Gene Therapy Zolgensma
The US Food and Drug Administration is investigating a serious tumour risk linked to Zolgensma, Novartis’s one-time gene therapy for spinal muscular atrophy, after two children’s tumours showed evidence that the treatment’s viral vector had inserted itself into their DNA.
The agency said in a safety communication on 6 November that it had received post-marketing reports of malignancies in patients treated with Zolgensma, including confirmed reports of product-related insertional oncogenesis involving the GLI1 gene. It is assessing whether regulatory action is needed and whether the drug’s long-term follow-up studies adequately address the risk.
The findings matter far beyond two patients. More than 6,000 children have received Zolgensma since it was first approved in the United States in 2019, and the cases are the first confirmed instance of a commercially approved gene therapy’s vector causing tumours in patients.
What the FDA found
Zolgensma is a one-time intravenous gene therapy given to children under two with spinal muscular atrophy, a rare genetic disorder that causes progressive muscle weakness. It uses an adeno-associated virus, or AAV, vector to deliver a working copy of the SMN1 gene.
Novartis disclosed that it had received nine reports of tumours in patients previously treated with Zolgensma since the therapy was first approved. The tumours were found in the central and peripheral nervous systems, the spinal and paraspinal regions, and the kidney.
The FDA said the risk applies to both of Novartis’s onasemnogene abeparvovec products — Zolgensma, given by intravenous infusion to children under two, and Itvisma, given by intrathecal injection to patients aged two and older — because the two products contain the same vector and construct. No cases of tumour formation have been reported after Itvisma, which was approved on 24 November 2025.
Two cases with a direct link
In two of the nine cases, molecular analysis of tumour 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. The FDA said it was also investigating a third tumour linked with GLI1.
England’s national multidisciplinary team for Zolgensma said histological examination had been completed for tumours in three of the nine children, and concluded that two of those tumours were linked to the treatment while the third appeared unrelated. The remaining six cases had not yet had histology results.
Novartis said both patients whose tumours showed evidence of vector integration had received treatment for their tumours and continued to be monitored. Reports cited by BioSpace suggested the two confirmed cases developed between 18 and 60 months after infusion — a year and a half to five years after the one-time dose.
“Patients and clinical trial participants receiving treatment with these products should be monitored for tumor formation,” the FDA said, adding that it is closely monitoring the risk in other similar AAV vector-based gene therapy programmes.
A risk the label still calls theoretical
The cases expose a gap in the drug’s existing prescribing information. Section 5.6 of Zolgensma’s US label states there is a “theoretical risk of tumorigenicity due to integration of AAV vector DNA” and that a causal relationship with the treatment has not been established — language that no longer reflects the confirmed cases.
As of Thursday evening, the label had not been updated. The FDA said it was expeditiously evaluating the adequacy of the current prescribing information and the long-term follow-up studies, and Novartis is conducting long-term safety studies.
The agency stressed that the overall benefits of both Zolgensma and Itvisma continue to outweigh their potential risks for their approved uses. Families of treated children should not stop any treatment, the FDA said, but should watch for signs of tumour formation and report suspected adverse reactions.
What happens next
The investigation lands in a year of heightened scrutiny of paediatric medicines. The FDA recently fast-tracked a paediatric sleep drug for children with insomnia, and the government has just made Medicare drug price negotiations permanent — signs of a regulator moving quickly on both access and safety.
For Novartis, the immediate questions are whether the FDA will require a label change, stronger warnings, or changes to the long-term monitoring of the thousands of children already treated. For families, the advice for now is vigilance rather than alarm: the confirmed cases remain rare — two in more than 6,000 treated children — but they are no longer theoretical.
Healthcare providers who see a tumour develop in a patient who received Zolgensma should contact Novartis Gene Therapies at 1-833-828-3947 or report the case to the FDA through MedWatch.
