FDA says it is investigating tumour reports in Novartis's Zolgensma

What the FDA said on 6 November

The agency's update describes a mechanism called insertional oncogenesis. Genetic material that a gene therapy delivers becomes part of a patient's DNA and drives abnormal cell growth.

In two cases, tests on tumour tissue found vector DNA inserted at the GLI1 gene, an oncogene that can drive cancer when abnormally activated. A third tumour linked to GLI1 is still under investigation. The tumours reported so far affected the central and peripheral nervous systems, the spinal and paraspinal regions, and the kidney.

Zolgensma's label already carries a boxed warning for serious liver injury and acute liver failure, including fatal cases. It also lists thrombocytopenia, thrombotic microangiopathy and the potential risk of tumorigenicity from AAV vector integration.

For now, the FDA says the benefits of Zolgensma and Itvisma outweigh the potential risks in their approved uses.

Nine reports, seven of them new

Novartis disclosed on 5 November that it had received nine reports of tumours in patients treated with Zolgensma since the therapy's approval in 2019. Seven of those cases were previously unknown, Endpoints News reported.

Two of the nine showed evidence that vector DNA had integrated into the patients' genomes. Both patients have received treatment and remain under medical monitoring, according to Novartis. More than 6,000 patients have received Zolgensma across clinical trials, managed access programmes and commercial treatment, the company says. STAT reported that an advocacy group and a Facebook page publicised the seven new cases on Thursday, after Novartis told neurologists earlier that week. The company has not said where the two new cases were reported, Times Now reported.

Zolgensma won US approval in May 2019 and costs $2.125 million for a one-time infusion. Itvisma, approved in November 2025, costs $2.59 million per treatment.

Why AAV vectors are the centre of the case

Children under two receive Zolgensma intravenously; patients aged two and older receive Itvisma by injection into the spinal canal.

The theoretical risk of tumour formation from vector integration was already in Zolgensma's prescribing information. What is new is the evidence. STAT reported that a series of cases this year has presented powerful evidence that AAVs can cause cancer. That evidence settles a debate that ran for two decades. Sam Mackenzie, a neurologist at the University of Rochester, told STAT: "It will change the calculus for some patients". The FDA said it is closely monitoring neoplasia risk in other AAV-based gene therapy programmes and referred to two technical reports on cancer cases with comparable treatments.

AAV vectors deliver genes in other approved therapies too, not only in Novartis's two products.

What it means for patients and for Itvisma

The FDA has determined that the neoplasia risk applies to both Zolgensma and Itvisma because they contain the same vector and construct. The agency says it has received no reports of neoplasia after Itvisma administration.

Zolgensma treats spinal muscular atrophy, a rare genetic disorder that progressively weakens muscles and often leads to death before age two if untreated. Itvisma carries a boxed warning for acute serious liver injury and elevated aminotransferases, and its label also lists peripheral sensory neuropathy and elevated cardiac troponin I.

The FDA said patients receiving either therapy need monitoring for tumour growth. SMA Europe, a patient group, urged Novartis to explain clearly what is known, what is still uncertain and what the findings could mean for children who have already received treatment. Novartis said in a statement: "Patient safety is our priority. In each case, we timely and appropriately notified health authorities and will continue to work with them on next steps."

The Zolgensma Group combines Zolgensma and Itvisma. It recorded $1.071 billion in sales in the first nine months of 2026, against $925 million in the same period of 2025.

What happens next

The FDA is still deciding whether to take regulatory action, and has not said what form it might take. It is also checking whether the long-term safety studies now under way can track the risk properly.

The FDA has not published a timeline for that decision. SMA Europe said regulatory authorities are examining the cases. Novartis said it will continue to work with health authorities on next steps.