Could a gene therapy used to treat spinal muscular atrophy (SMA) carry a potential tumour risk? Novartis has acknowledged nine reports of tumours in children previously treated with its gene therapy onasemnogene abeparvovec (Zolgensma), including two cases showing evidence of the therapy’s genetic material integrating into patients’ DNA.
Novartis Reports Nine Tumour Cases
According to the pharmaceutical company, it has received nine tumour reports since Zolgensma was first approved in 2019. Of these, two cases have shown evidence of vector DNA integration into the patients’ DNA.
A Novartis spokesperson told MedPage Today that both patients received treatment and continue to undergo monitoring. The company also stated that it had notified the relevant health authorities and would continue working with regulators to determine the next steps.
However, Novartis has not disclosed when the tumours developed or were identified in the remaining seven cases.
How Does Zolgensma Work?
Zolgensma is an adeno-associated virus (AAV) vector-based gene therapy approved in 2019 for children under two years of age with spinal muscular atrophy and bi-allelic SMN1 mutations.
SMA is a genetic disorder caused by insufficient levels of survival motor neuron (SMN) protein, which is essential for motor neuron function. The condition results from deletions or mutations in the SMN1 gene. Although the closely related SMN2 gene produces some functional SMN protein, the amount is usually insufficient.
Zolgensma works by delivering a functional copy of the SMN1 gene through an AAV vector, helping the body produce the essential SMN protein.
Prescribing Information Already Notes Potential Tumour Risk
The integration of AAV vector DNA into a patient’s genome carries a theoretical risk of tumour development. Novartis noted that the potential risk of tumours associated with vector integration is already included in Zolgensma’s prescribing information.
Meanwhile, concerns about the reported cases have also surfaced among patient advocacy groups and families. SMA Europe, an umbrella organisation representing SMA patient groups across Europe, acknowledged the reports and said regulatory authorities were assessing the available evidence to determine whether further action was necessary.
In the United States, the Muscular Dystrophy Association (MDA) said it was seeking additional information, reviewing available scientific and safety data with clinical and research experts, and had contacted Novartis. The organisation also highlighted that information about the timing and nature of the tumours and possible long-term monitoring remains limited.
Earlier Research Examined Tumour Cases After Gene Therapy
Previous case reports have also examined tumours in patients who received Zolgensma. A 2023 report described a 16-month-old boy with SMA who developed an epithelioid neoplasm of the spinal cord 14 months after treatment. However, researchers considered the findings inconclusive.
Similarly, a 2025 case report documented a pilocytic astrocytoma in a child with SMA who had received Zolgensma. Molecular analysis suggested that the tumour’s development was not causally linked to the gene therapy.
Furthermore, researchers earlier identified AAV vector integration in a brain tumour in a five-year-old boy with severe mucopolysaccharidosis type I (Hurler syndrome) who had received a different AAV-based gene therapy. The findings were published in the New England Journal of Medicine.
More Than 6,000 Patients Have Received Zolgensma
Novartis stated that more than 6,000 patients have received Zolgensma through clinical trials, managed access programmes and commercial treatment. The company added that it continuously monitors the safety of its medicines, evaluates new safety information and assesses reported cases.
The therapy has also faced regulatory scrutiny in the past. Following its approval, the US Food and Drug Administration (FDA) criticised Novartis’ AveXis unit over data manipulation that affected the accuracy of animal product-testing results.
The latest tumour reports have renewed attention on the long-term safety monitoring of gene therapies, while regulatory authorities continue to assess the available evidence. As reported by medpagetoday.com, Novartis continues to monitor the reported cases and evaluate emerging safety information in coordination with regulatory authorities to assess the potential risks associated with Zolgensma.