Zolgensma and Cancer Concerns: What the FDA Is Investigating in Children

TVS News AI, editorially supervised, presents Zolgensma and Cancer Concerns: What the FDA Is Investigating in Children.

A few years ago, Zolgensma cost around two million euros, making it the world's most expensive drug. Now, a different number is at the center of attention: The US Food and Drug Administration is investigating reports of cancer in several children who had been treated with this therapy.

The report concerns a one-time gene therapy that has been approved in the United States and Europe since around 2020 for children under two. Zolgensma treats spinal muscular atrophy, a rare genetic disease that causes muscle wasting, among other things, and often leads to death before the age of two.

For families and treating teams, the central distinction is important: The FDA is investigating a possible link between the treatment and the reported tumors. According to the information available, such a link has not been confirmed. At the same time, the agency says that Zolgensma's expected benefits outweigh its possible risks overall.

Three Tumor Cases Put the Oncogene GLI1 in Focus

What is known so far

According to the FDA, the tumors that appeared after the therapy affected the central and peripheral nervous systems, the spinal column and the kidney. In three cases, the oncogene GLI1 was involved. This gene can contribute to the development of cancer.

The agency is therefore investigating a specific biological approach rather than simply searching for side effects in general. In two of the three cases, analyses found DNA from the virus used in the therapy in the tumor tissue. The third case is still under investigation.

This does not mean that the treatment definitively explains the cause of the tumors. It only shows where DNA from the therapy virus was detected in the tumor tissue. The exact relationship between this DNA, integration into the genome and tumor formation remains under investigation.

How Zolgensma Works

Zolgensma is intended to treat the genetic cause of spinal muscular atrophy. To do this, the child is given a single intravenous infusion. The therapy replaces the function of the missing or nonfunctioning SMN1 gene.

Modified viruses, known as AAV vectors, serve as gene-delivery vehicles. They deliver a healthy copy of the SMN1 gene into the body's cells. These AAV vectors are at the center of the current safety question. According to the source text, they are also used as gene-delivery vehicles in other gene therapies.

More Than 6,000 Treated Patients and Nine Tumor Reports

The extent of the experience

The patient organization SMA Europe quotes a letter from Novartis saying that more than 6,000 patients have been treated with Zolgensma since 2019. The company had received tumor reports for a total of nine patients.

The reports can therefore be placed in the broader context of treatment. The source text cites nine tumor reports and three cases in which GLI1 was involved. However, it does not turn this into a confirmed total of nine cases of cancer caused by Zolgensma. The reports, investigated cases and the oncogene GLI1 are therefore considered separately.

According to the Novartis letter cited, vector DNA was integrated into the genome in two of the affected patients. They were treated and will continue to be monitored. The company also notes that the prescribing information warns of the potential risk of tumors caused by vector integration.

What the FDA Is Additionally Investigating

The drug regulator explicitly refers to two expert reports on cancer cases involving other, comparable AAV-based gene therapies. It is therefore monitoring not only Zolgensma, but also the risk of neoplasms, including malignant tumors, in similar gene therapy programs.

Whether regulatory action is required is under investigation. At present, the FDA concludes that Zolgensma's benefits outweigh its possible risks. This assessment does not replace a final investigation of the reported cases, but it shows the position the agency currently takes publicly.

The Report Is an Investigation, Not Proof of Harm

What is certain

It is certain that the FDA is investigating reports of cancer in several children treated with Zolgensma. The tumors affected the central and peripheral nervous systems, the spine and the kidney. In two cases, DNA from the AAV vector used in the therapy was found in the tumor tissue.

Just as clear is what remains unresolved: The third GLI1 case is still being investigated. The source text does not provide a confirmed cause, a final number of cases investigated or a date for the results.

A fair assessment

The story deserves attention because it identifies a possible mechanism and specific molecular findings. The strongest argument against premature conclusions is the large treated population of more than 6,000 patients against only nine tumor reports — although these reports do not automatically establish confirmed causality.

At the same time, the FDA continues to assess Zolgensma's possible benefits as greater than its possible risks. Families therefore need to view the report neither as an all-clear nor as proof of harm. It is the beginning of a regulatory investigation whose key questions will become apparent through the three GLI1 cases, the two detections of viral DNA and the continued monitoring of similar gene therapies.