FDA Investigates Serious Cancer Risk Linked to Zolgensma Gene Therapy

What was announced

The FDA issued a safety communication regarding postmarketing adverse event reports of tumors in patients treated with Zolgensma. Zolgensma is an adeno-associated virus vector-based gene therapy approved to treat spinal muscular atrophy in pediatric patients under two years old. Reports include tumors in the central and peripheral nervous systems, spinal or paraspinal regions, and kidney.

Laboratory analysis of three tumor cases involved the GLI1 gene, an oncogene capable of causing cancer when abnormally activated. In two cases, researchers confirmed that Zolgensma vector DNA inserted into the patient's DNA near or within GLI1. The FDA noted that this risk also applies to Itvisma, an intrathecal gene therapy approved in November 2025 for older spinal muscular atrophy patients, because both products share the same vector construct. No tumors have been reported after Itvisma treatment to date.

What it means

The FDA is evaluating whether regulatory actions, such as updates to prescribing information, are appropriate. Current U.S. prescribing information lists a theoretical risk of DNA integration for these products under Warnings and Precautions. The agency is now assessing whether existing warnings and long-term follow-up safety studies conducted by sponsor Novartis Gene Therapies, Inc. are adequate to address the confirmed cases of insertional oncogenesis.

Despite the investigation, the agency stated that the overall benefits of Zolgensma and Itvisma continue to outweigh their potential risks for their approved uses. The FDA recommends that healthcare providers monitor patients and trial participants for tumor formation. Providers who identify a tumor in a Zolgensma patient can report it directly to Novartis at 1-833-828-3947.

What the announcement does not tell us

The safety communication does not state what specific regulatory changes or label updates the FDA might require. It does not explain the biological mechanism behind GLI1 overexpression in the third reported tumor case, which remains under investigation.

The alert also does not reveal how many total postmarketing cases of tumor formation have been reported to date, nor does it detail the medical outcomes or current conditions of the affected patients. Finally, the announcement does not specify how long patients should be monitored for tumor growth after receiving treatment.