US regulator investigates tumour risk in children given Novartis gene therapy

The FDA is examining a possible cancer-related risk linked to Zolgensma, Novartis’s gene therapy for children under two with spinal muscular atrophy. The concern is neoplasia, meaning abnormal tumour growth, including malignancy. The investigation matters because Zolgensma is a one-time treatment given to thousands of children.

Novartis disclosed two cases in which doctors found evidence that the modified virus used by Zolgensma had inserted genetic material into the children’s own DNA. The company has received nine tumour reports overall among patients treated since the therapy was approved in 2019. These findings suggest a possible connection, but they do not establish that Zolgensma caused every reported tumour.

The FDA said Zolgensma’s benefits still outweigh its potential risks for approved uses. However, it is evaluating whether regulatory action is appropriate. The agency also said no neoplasia cases had been reported after Itvisma, Novartis’s other spinal muscular atrophy gene therapy.

Neoplasia is the formation of abnormal tissue caused by cells growing or multiplying in an uncontrolled way. The resulting growth is called a tumour or neoplasm. Neoplasms can be benign, meaning non-cancerous, or malignant, meaning cancerous. The distinction matters because malignant tumours can invade nearby tissue and spread elsewhere in the body.

In this article, the FDA uses neoplasia as the broader concern, covering tumour formation including malignancy. Novartis reported nine tumour cases among patients previously treated with Zolgensma. In two cases, doctors found evidence that the therapy’s viral carrier had inserted genetic material into the patients’ DNA. That finding could help explain how abnormal growth might occur, but it does not prove causation.

The FDA is assessing the risk while saying the therapy’s benefits continue to outweigh potential risks for approved uses. Zolgensma’s prescribing information already includes the potential tumour risk. The investigation will help determine whether warnings or other regulatory steps are needed.

Novartis said it had received nine reports of tumours in patients previously treated with Zolgensma since the therapy was first approved in 2019. The treatment had been given to more than 6,000 children. Thus, the article reports nine tumour cases within that treated population, although it does not provide a confirmed rate or establish that Zolgensma caused all of them.

The most concerning detail involves two of the nine cases. Doctors found evidence that the modified virus used to deliver the working gene had inserted its genetic material into the patients’ own DNA. Such insertion raised the possibility of a connection between the treatment and tumour formation, but the article does not give enough information to determine causation or compare the cases with background tumour risk.

The FDA continues to say Zolgensma’s benefits outweigh potential risks for approved uses. It is investigating the possible risk and deciding whether regulatory action is appropriate. The article also notes that no neoplasia cases had been reported after Itvisma.

Both Zolgensma and Itvisma are Novartis gene therapies for spinal muscular atrophy, but they differ in how and when they are given. Zolgensma is administered through an intravenous infusion and is approved for paediatric patients younger than two. Itvisma is administered through an intrathecal injection and is used for adults and children aged two or older.

Their delivery routes also reflect different treatment groups. Zolgensma uses a modified virus to deliver a working copy of a gene into cells. The article does not describe Itvisma’s delivery mechanism beyond identifying its intrathecal route. No neoplasia cases had been reported after Itvisma, according to the FDA, although the agency is evaluating potential risks for both therapies.

The FDA said the benefits of both products continue to outweigh their potential risks for approved uses. However, it is considering whether regulatory action is appropriate because of the Zolgensma tumour reports. Zolgensma’s prescribing information already includes the potential tumour risk.

Zolgensma uses a modified virus as a carrier to deliver a working gene into cells. In two reported tumour cases, doctors found evidence that this carrier had inserted its genetic material into the patients’ DNA. That matters because DNA helps control how cells function, divide and respond to growth signals.

If inserted material disrupts a gene that normally restrains cell growth, or changes how nearby genes work, a cell could potentially begin multiplying abnormally. That is a recognised biological concern with genetic insertion. However, the article reports evidence of insertion, not proof that insertion caused the tumours. It also does not explain the exact genetic changes in either child.

The FDA is therefore investigating the possible link rather than announcing a confirmed cause. Novartis said the potential tumour risk already appears in Zolgensma’s prescribing information. The FDA continues to judge the benefits favourable for approved uses while assessing whether further action is needed.

The FDA’s investigation could lead to regulatory action if the agency decides the tumour risk requires a stronger warning, altered prescribing information, additional monitoring, or changes to how the therapy is used. The article does not say which action, if any, will occur. It only says the FDA is evaluating whether action is appropriate.

One important point is that the potential tumour risk is already included in Zolgensma’s prescribing information, according to Novartis. The agency is reviewing new evidence: two cases in which doctors found that the therapy’s modified viral carrier had inserted genetic material into patients’ DNA. Novartis has reported nine tumours overall among treated patients.

For now, the FDA says the benefits of Zolgensma and Itvisma continue to outweigh their potential risks for approved uses. Future decisions could depend on the agency’s assessment of the cases and the possible genetic mechanism. Patient advocates are also pressing for clearer information about what is known and uncertain.

Spinal muscular atrophy, or SMA, is a rare inherited disorder that causes progressive weakness because nerve cells controlling voluntary movement do not function properly. The article identifies SMA as the condition treated by Novartis’s gene therapies and describes it as a rare muscle disorder. In severe childhood forms, weakness can affect movement, swallowing and breathing.

A gene therapy aims to address the underlying genetic problem rather than only manage symptoms. Zolgensma uses a modified virus to deliver a working copy of a gene into cells. Those cells may then make the protein needed for the affected nerve cells to survive and function. This is why delivering a working gene can help children with SMA, although the article does not describe clinical outcomes in individual patients.

Zolgensma is approved for paediatric patients under two and has been given to more than 6,000 children. The FDA says its benefits outweigh potential risks while investigating tumour reports. Itvisma is the other Novartis therapy, used from age two onward and in adults.