The U.S. Food and Drug Administration said on Friday, November 6, that it is investigating a serious risk of cancer linked to Zolgensma, the one-time gene therapy used to treat babies and toddlers with spinal muscular atrophy, after post-marketing reports of tumours in treated patients — including cases in which laboratory analysis found the therapy's own genetic material inserted into a known cancer gene.

Source: U.S. Food and Drug Administration

The FDA's safety communication, published on November 6, 2026, says the agency has received post-marketing adverse-event reports of malignancies in patients treated with Zolgensma, including confirmed reports of what scientists call insertional oncogenesis — a tumour caused when a delivery virus inserts its genetic cargo into the patient's own DNA in a place that switches a cancer-promoting gene on.

What the FDA found in the tumours

According to the FDA, the reported tumours include cancers of the central and peripheral nervous systems, tumours in the spinal and paraspinal regions, and a kidney tumour. Three of the cases involved tumours associated with GLI1 (Glioma-Associated Oncogene Homolog 1), a gene that can drive cancer when it is overexpressed or abnormally activated. In two of those three cases, molecular analysis of the tumour tissue demonstrated that DNA from Zolgensma's adeno-associated virus (AAV) vector had integrated into the patient's genome, with the promoter region of the therapy's construct inserted upstream of, or within, the GLI1 gene. How GLI1 was switched on in the third case is still under investigation, the agency said.

Novartis, the Swiss drugmaker that sells Zolgensma, disclosed the cases a day earlier. The company said it had received nine reports of tumours in previously treated patients since the therapy was first approved in 2019, and that of the tumours examined in detail, two showed evidence of the vector integration while a third appeared unrelated. An update from England's national multidisciplinary team for Zolgensma, dated November 4, reached the same split: tissue examination had been completed for three of the nine children, two tumours were linked to the treatment, and one appeared unrelated. Novartis says more than 6,000 patients have received Zolgensma through clinical trials, access programmes and commercial use.

Source: The Hindu BusinessLine

Two products, one delivery virus

The FDA said the risk applies to both of Novartis's onasemnogene abeparvovec products, because they contain the same vector and construct. Zolgensma is given as an intravenous infusion to children under 2 years of age with spinal muscular atrophy (SMA) and was first approved on May 24, 2019. Itvisma, given by intrathecal injection into the spinal canal, treats SMA in adults and in children 2 years and older and was first approved on November 24, 2025. The agency stressed that no cases of tumour formation have been reported after Itvisma treatment so far. It is also monitoring other AAV gene-therapy programmes, and noted two published reports of the same kind of event elsewhere in the field — a GLI1 integration case in the FBX-101 programme and a PLAG1 integration case in the RGX-111 programme.

A risk the label still calls 'theoretical'

The current U.S. prescribing information for both products already mentions this danger — but only as a possibility. Under Warnings and Precautions it states that there is a 'theoretical risk of tumorigenicity due to integration of AAV vector DNA into the genome.' Coverage of Novartis's disclosure noted that the label also says a causal relationship with Zolgensma has not been established — wording that now sits uneasily beside two laboratory-confirmed cases. One parent whose child saw a neurologist on November 4 told BioSpace the two confirmed cases appeared to have developed between 18 and 60 months after the one-time infusion, which would mean the risk can surface anywhere from about a year and a half to five years after treatment.

What happens next

The FDA said it is 'expeditiously evaluating' whether the current prescribing information and the long-term follow-up studies Novartis is required to run are adequate to investigate and reduce the risk. Novartis is conducting long-term follow-up safety studies of treated patients, and the agency said patients and clinical-trial participants receiving either product should be monitored for tumour formation. Doctors who see a tumour develop in a patient who received Zolgensma are asked to contact Novartis Gene Therapies at 1-833-828-3947, or the FDA at 1-800-FDA-1088 or through its MedWatch reporting site.

Spinal muscular atrophy is a rare genetic disorder that destroys the motor neurons controlling movement, causing progressive muscle weakness; before gene therapy, its most severe form was a leading genetic cause of infant death. Zolgensma works by delivering a working copy of the SMN1 gene — the gene SMA patients are missing — using the AAV virus as the delivery vehicle. That delivery step is exactly what investigators are now examining: the same insertion into a patient's DNA that makes the one-time treatment durable is the step the FDA says went wrong, in the wrong place, in at least two children.

For families — including Punjabi and other South Asian families in the United States whose children have received SMA gene therapy — the practical message from regulators is narrow and specific: the treatment is not being withdrawn, its benefits are still judged to outweigh its risks, and the new instruction is vigilance. Any tumour in a treated patient should be reported through the numbers above, because each report is part of how the FDA will decide whether the label's 'theoretical' warning becomes something stronger.