What the FDA announced
The US Food and Drug Administration said on Friday, 6 November 2026, that it is investigating a serious risk of malignancy linked to Zolgensma, Novartis' one-time gene therapy for spinal muscular atrophy (SMA), after nine children treated with the drug were reported to have developed tumours. In two of the cases, laboratory analysis found evidence that the therapy's viral delivery vehicle had inserted its genetic material into the patients' own DNA — a process known as insertional oncogenesis.
The announcement, published on the FDA's safety pages, marks a significant escalation in the scrutiny of a treatment given to more than 6,000 children worldwide since its approval in 2019. The agency said it was evaluating whether regulatory action was appropriate, while stressing that the overall benefits of the therapy continue to outweigh its potential risks for its approved uses.
Nine tumour reports, three linked to the same gene
According to the FDA, the postmarketing reports of tumour formation — known as neoplasia — include tumours of the central and peripheral nervous systems, the spinal and paraspinal regions, and the kidney. Three of the cases involved tumours associated with GLI1, an oncogene that can cause cancer when it is overexpressed or abnormally activated.
In two of those three cases, molecular analysis of tumour tissue demonstrated that the Zolgensma adeno-associated virus (AAV) vector DNA had integrated into the host genome, with the promoter region of the therapy's genetic construct inserted upstream of or within the GLI1 gene. The mechanism of GLI1 overexpression in the third case remains under investigation, the FDA said.
Novartis, which disclosed the two confirmed cases earlier on Friday, said it had received nine reports of tumours in patients previously treated with Zolgensma since the therapy was first approved. In another case, pathology findings suggested the tumour was unrelated to treatment, and a causal relationship has not been established for the remaining cases. The two patients whose tumours showed vector integration received treatment for their tumours and remain under monitoring.
Why this matters: Zolgensma was approved in the United States in May 2019 as a one-time treatment for children under two with SMA, a rare and often fatal genetic disease that destroys the nerve cells controlling movement. A single intravenous infusion delivers a working copy of the SMN1 gene. The possibility that the delivery vehicle itself could switch on a cancer-causing gene was long listed in the prescribing information only as a theoretical risk — the new cases are the first in which that mechanism has been confirmed in patients.
A risk the label still calls theoretical
The current US prescribing information for Zolgensma describes a "theoretical risk of tumorigenicity due to integration of AAV vector DNA into the genome" under its warnings and precautions. The FDA said it was "expeditiously evaluating the adequacy of the current prescribing information and long-term follow-up studies" in light of the new safety information.
Novartis said the potential risk of tumours was already included in Zolgensma's prescribing information and that it had notified health authorities "in a timely and appropriate manner" in both confirmed cases. The company is conducting long-term follow-up safety studies of treated patients, the FDA said.
"The overall benefits of Zolgensma and Itvisma continue to outweigh their potential risks for their approved uses, though FDA is investigating the identified risk of neoplasia, including malignancy, with serious outcomes, and is evaluating whether regulatory action is appropriate."
— US Food and Drug Administration, 6 November 2026
Patient advocates have pressed for more openness. SMA Europe, a patient advocacy organisation, had urged Novartis to provide information on what is known, what is uncertain, and what the findings could mean for children who have already received the treatment. Advocates have also complained that the company was slow to share information about the cases, Reuters reported.
Itvisma, the sister therapy, is also under review
The FDA said it had determined that the risk of neoplasia applies to both products containing the same onasemnogene abeparvovec vector and construct: Zolgensma, given by intravenous infusion to children under two, and Itvisma, given by injection into the spinal fluid for SMA patients aged two and older. Itvisma was approved on 24 November 2025.
No cases of neoplasia have been reported following Itvisma administration to date, the agency said. It added that it was closely monitoring the risk in other similar AAV vector-based gene therapy programmes, and pointed to two published reports of vector integration-driven cancer in other programmes — a GLI1 integration event in the FBX-101 programme and a PLAG1 integration event in the RGX-111 programme.
| Product | How it is given | Who it is for | Approved | Tumour reports |
|---|---|---|---|---|
| Zolgensma | Intravenous infusion, one time | Children under 2 with SMA | 24 May 2019 | 9 reports; 2 confirmed vector integration |
| Itvisma | Injection into spinal fluid | SMA patients aged 2 and over | 24 Nov 2025 | None reported to date |
What this means for families
The FDA's message to families is, for now, one of vigilance rather than alarm. The agency said patients and clinical trial participants receiving these products should be monitored for tumour formation, and it asked healthcare providers to report any suspected adverse reactions through its MedWatch system or directly to Novartis.
For the more than 6,000 children who have already received Zolgensma, the practical question is what monitoring should look like — and how long it should last. The confirmed cases are understood to have developed months to years after the single infusion, which is why long-term follow-up studies are central to the FDA's review. Novartis has not provided details on where the two new cases occurred.
What is not yet known: the FDA has not said how many of the nine reported tumours were malignant, what regulatory action — if any — it may take, or whether the prescribing information will be updated. A causal relationship has not been established for six of the nine cases, and the mechanism in the third GLI1 case is still under investigation. The European Medicines Agency did not immediately respond to a request for comment from Reuters.
What happens next
The FDA said it was evaluating the adequacy of the current prescribing information and of Novartis' long-term follow-up studies, and would decide whether regulatory action was appropriate. Possible outcomes range from a label update that replaces the "theoretical" wording with a confirmed risk, to strengthened monitoring requirements for treated patients. Any change would also have implications beyond Zolgensma: AAV vectors are the delivery system for a growing number of approved gene therapies, and regulators in the US and Europe will be watching how the agency handles confirmed cases of vector integration causing cancer in a commercial product.
For now, the therapy remains available, and the FDA has not restricted its use. The investigation is a reminder of the bargain at the heart of gene therapy: a single, potentially life-saving dose, carrying risks that can take years to surface — and that only long-term follow-up can fully reveal.
Frequently asked questions
What is Zolgensma?
Zolgensma is a one-time gene therapy for spinal muscular atrophy, a rare genetic disease that weakens and destroys the muscles. It uses a modified virus, an AAV vector, to deliver a working copy of the SMN1 gene into the patient's cells. It was approved in the US in May 2019 for children under two.
How many children have been affected?
Novartis has received nine reports of tumours in patients previously treated with Zolgensma. In two cases, analysis confirmed that the therapy's viral vector had inserted itself into the patients' DNA near the GLI1 cancer gene. More than 6,000 children have received the treatment worldwide.
Does this mean Zolgensma causes cancer?
Not in every case. A causal link has been confirmed in two of the nine reported cases. In one case the tumour appeared unrelated to treatment, and for the remaining cases a causal relationship has not been established. The FDA is investigating and has not yet decided on regulatory action.
What should families of treated children do?
The FDA says patients receiving these products should be monitored for tumour formation. Families with concerns should speak to their child's treating physician, and healthcare providers can report suspected adverse reactions to the FDA's MedWatch programme or to Novartis.
Key takeaways
- The FDA is investigating a serious risk of malignancy linked to Zolgensma, Novartis' one-time gene therapy for spinal muscular atrophy, after nine tumour reports in treated children.
- In two cases, laboratory analysis confirmed that the therapy's viral vector had inserted its DNA into the patients' genomes near the GLI1 cancer gene — a risk the drug's label still describes as theoretical.
- The risk applies to both onasemnogene abeparvovec products, Zolgensma and the newer Itvisma, though no tumour cases have been reported after Itvisma.
- The FDA says the benefits of both therapies continue to outweigh the risks and has not restricted their use, but it is evaluating whether regulatory action is appropriate.
- More than 6,000 children have received Zolgensma since 2019; long-term monitoring of treated patients is now central to the investigation.
BreakingHour will update this article as the FDA investigation develops and as Novartis or European regulators respond.
