Gene Therapy Under Scrutiny After Nine Tumor Reports

Novartis said Thursday it has received reports of nine tumors in patients previously treated with Zolgensma, its gene therapy for spinal muscular atrophy (SMA). The company said two cases showed evidence that DNA from the therapy’s viral vector had integrated into patients’ DNA, while the available information does not establish whether the treatment caused either tumor.

In comments to MedPage Today, a Novartis spokesperson said the reports had been received since Zolgensma’s first approval in 2019. The company said that in two of the nine cases, testing found evidence of vector DNA integration. It did not provide details about when those tumors developed, what types they were, or how the patients were doing beyond saying they had undergone treatment and remained under monitoring.

Novartis said it had notified health authorities in both cases and would work with regulators on next steps. The company described the reports as part of its ongoing safety monitoring. It said more than 6,000 patients had received Zolgensma through clinical trials, managed access programs and commercial treatment. That total does not, by itself, indicate the rate of tumor reports or establish a comparison with untreated patients.

The disclosure follows concern among SMA advocates after some families reportedly heard about tumor reports from doctors. SMA Europe said regulatory authorities were assessing the available evidence. In the United States, the Muscular Dystrophy Association said it was seeking information, reviewing available safety and scientific data with experts, and had contacted Novartis.

Safety Monitoring for Zolgensma Patients

The reports matter because Zolgensma is used to treat a serious inherited disease in children, and the possibility of tumors linked to genetic material from a gene therapy is a significant safety question for patients, families and clinicians. The finding of vector DNA integration in two cases warrants evaluation, but integration alone does not show that the therapy caused a tumor.

Regulators and researchers will need case details to assess whether the tumors are biologically connected to treatment, whether any pattern exists and whether changes to monitoring or product information are appropriate. For families whose children have received the therapy, the disclosure may prompt questions about follow-up. The source material does not establish a new monitoring recommendation or a change in Zolgensma’s availability.

Zolgensma and the Tumor Risk

Zolgensma, whose generic name is onasemnogene abeparvovec, uses an adeno-associated virus (AAV) vector to deliver a working copy of the SMN1 gene. SMA results from reduced levels of survival motor neuron protein, commonly because of changes or deletions in both copies of SMN1. The treatment was approved in 2019 for pediatric patients younger than 2 with SMA and bi-allelic SMN1 mutations.

The therapy’s prescribing information already describes a theoretical risk of tumorigenicity if vector DNA integrates into a patient’s genome. Earlier reports involving individual patients do not settle the question raised by the new disclosure. A 2023 case report described a spinal cord epithelioid neoplasm diagnosed 14 months after treatment in a 16-month-old boy, but considered the finding inconclusive. A 2025 report described a pilocytic astrocytoma in a treated child; molecular analysis suggested its development was causally independent of the therapy.

Separately, researchers reported vector integration in a brain tumor in a child with Hurler syndrome who had received a different AAV gene therapy. That case is relevant to wider questions about AAV-based treatments, but it involved another disease and another therapy. It does not establish the cause of any of the nine tumors reported to Novartis.

“We understand that the relevant regulatory authorities are actively involved and are currently assessing the available evidence and determining what further steps may be needed.”

— SMA Europe

Key Details Still Missing

The public disclosure does not specify the tumor types, patients’ ages, timing of diagnosis or the clinical circumstances for the nine reports. Novartis also did not explain when the other seven tumors were identified or whether testing found vector integration in those cases. It is unclear whether all reports have been independently reviewed or whether they represent a consistent clinical pattern.

The evidence described by the company establishes vector integration in two patients, but the source material does not establish that integration caused either tumor. It also gives no comparison rate for tumor diagnoses among treated and untreated patients. Regulators’ assessment, including whether the reports change the product’s safety guidance, remains pending.

Regulators Review the Case Evidence

Health authorities are assessing the available evidence, according to SMA Europe, and Novartis said it would continue working with them. The next meaningful developments are likely to include more detail about the cases and any regulatory conclusions or advice for clinicians and patients. No specific decision date or change to the prescribing information was reported.

The MDA said it was consulting clinical and research experts and had contacted Novartis. Until further information is available, the reasons for the tumors and any implications for monitoring remain unresolved. Patients and families should direct individual treatment or follow-up questions to a qualified health professional familiar with their care.

Key Questions

How many tumor reports did Novartis disclose?

Novartis said it had received nine reports of tumors in patients previously treated with Zolgensma since the therapy’s first approval in 2019.

Do the reports show that Zolgensma caused tumors?

No causal link is established by the information disclosed. Novartis said two cases showed evidence of vector DNA integration, but that finding alone does not prove the therapy caused either tumor.

What is known about the two cases with vector integration?

The company said both patients underwent treatment and continue to be monitored. It did not publicly provide the tumor types, diagnosis dates or further clinical details.

Are regulators reviewing the reports?

SMA Europe said relevant regulatory authorities were assessing the available evidence. Novartis said it had notified health authorities in the two cases with evidence of vector integration and would work with them on next steps.

Has guidance for Zolgensma patients changed?

The source material reports no change to the prescribing information or new monitoring recommendation. The company’s prescribing information already describes a theoretical tumor risk from integration of AAV vector DNA.

Source: medpagetoday.com