FDA Investigates Tumors Linked to Zolgensma After Gene Integration Found in Two Cases
Key Facts
The U.S. Food and Drug Administration said on November 6, 2026, that it is investigating the risk of tumors, including malignant tumors, in patients who received Zolgensma to treat spinal muscular atrophy. The agency said its review includes tumor cases in the central and peripheral nervous systems, the spinal and surrounding areas, and the kidneys. In the molecular details, it said three cases involved tumors linked to the GLI1 gene. Analysis of tumor tissue in two of those cases showed integration of the vector DNA used in Zolgensma into the patient’s genome, near or within the gene. The FDA said the mechanism behind increased GLI1 expression in the third case remains under investigation, as it assesses whether current regulatory information is sufficient and whether action is needed.
The FDA statement distinguishes between finding vector integration in a patient’s genome and identifying the mechanism in cases that remain unclear: the molecular finding it reported applies to two cases, while the explanation for the third remains under investigation. U.S. prescribing information already included a warning about a theoretical risk of tumor formation due to integration of AAV vector DNA into the genome. The warning places gene integration among the potential risks the agency is monitoring, but it does not by itself identify the cause of every tumor in the cases reported. The FDA’s review includes the adequacy of information in the products’ labeling, as well as safety studies and long-term follow-up. The agency did not announce a change to the approved use in its statement and said the overall benefits of Zolgensma and Itvisma continue to outweigh potential risks in their approved indications.
The review also covers Itvisma, another Novartis treatment for spinal muscular atrophy, because the two products contain the same vector and genetic construct, according to the FDA. Zolgensma is given by intravenous infusion to children under 2 years old with the disease, while Itvisma is administered by intrathecal injection to adults and children aged 2 years and older. The agency said it had received no reports of tumors following Itvisma administration as of the date of its statement. Itvisma received its initial approval on November 24, 2025, according to the FDA, while the agency was assessing the adequacy of its labeling and long-term follow-up studies. The treatments’ shared vector and genetic construct broaden the scope of the safety review, while their age groups and methods of administration differ.
Zolgensma received FDA approval on May 24, 2019, when the agency described it as the first gene therapy approved for children under 2 years old with spinal muscular atrophy, an inherited disease it said was a leading cause of infant deaths. Since its launch, the treatment has reached more than 6,000 patients worldwide through the third quarter of 2026, according to Novartis’ interim financial report. Zolgensma franchise sales were $404 million in the third quarter of 2026, compared with $301 million in the third quarter of 2025, a 34% increase in dollars year over year. The investigation comes as a widely used treatment has posted higher sales over the comparison period and the agency reviews related safety data. Novartis shares closed at $162.55 on November 6, 2026, according to EL7 data.
The FDA recommended monitoring patients and clinical trial participants receiving Zolgensma or Itvisma for tumor formation. It said Novartis is conducting long-term safety follow-up studies, which are among the information the agency is reviewing. The FDA is also assessing whether the current labeling for both treatments is adequate and whether the evidence warrants regulatory action. It said the mechanism behind increased GLI1 expression in the third case remains under investigation, without giving a timeline for completing that work. For now, the agency says the overall benefits of both products continue to outweigh potential risks for their approved uses.