Novartis has confirmed nine instances—seven of them newly disclosed—in which tumors have developed in children treated with its marketed spinal muscular atrophy gene therapy Zolgensma (onasemnogene abeparvovec-xioi). [Rost-9D/Getty Images]
Novartis has confirmed nine reports—seven of them newly disclosed—in which tumors have developed in children treated with its marketed spinal muscular atrophy gene therapy Zolgensma® (onasemnogene abeparvovec-xioi).
“Of those, two cases to date have shown evidence of vector integration into the DNA of the patients. In both cases, the patients underwent treatment and continue to be monitored,” Novartis said in a statement furnished to GEN and other news outlets.
“Patient safety is our priority. In each case, we timely and appropriately notified health authorities and will continue to work with them on next steps,” the pharma giant added.
To date, Novartis stated, Zolgensma has been used to treat more than 6,000 patients worldwide across clinical trials, managed access programs, and commercial treatment.
The statement added: “The potential risk of tumors due to vector integration is currently included in the Zolgensma prescribing information.”
Zolgensma is an adeno-associated virus (AAV) vector-based gene therapy indicated for the treatment of pediatric patients less than two years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
Zolgensma is designed to address the genetic root cause of SMA by replacing the function of the missing or nonworking SMN1 with a new working copy of the gene delivered into a patient’s cells. The gene therapy consists of a recombinant, non-replicating AAV serotype 9 (AAV9) vector whose DNA persists largely in episomal form, according to the therapy’s prescribing information label.
Random integration of recombinant AAV vector DNA into human DNA has been reported with Zolgensma and in published studies about other AAV gene therapies, Novartis has acknowledged.
“The clinical relevance of individual integration events is unknown, but it is acknowledged that individual integration events could potentially contribute to a risk of tumorigenicity. Cases of tumor have been reported in patients who received Zolgensma post-approval,” the label added.
‘Theoretical risk’
Zolgensma’s prescribing label includes a section titled “AAV Vector Integration and Risk of Tumorigenicity.” That section, however, states: “There is a theoretical risk of tumorigenicity due to integration of AAV [adeno-associated virus] vector DNA into the genome.”
The label urges prescribers to report cases of tumors in patients who received Zolgensma to Novartis.
Novartis’ statement followed a statement issued Thursday by the Muscular Dystrophy Association (MDA). In the MDA statement, the association acknowledged awareness of reports about tumors developing in Zolgensma patients.
MDA stated that it “understand[s] that this raises questions and concerns for families, particularly those who have made important treatment decisions for themselves or their children. We take these reports seriously and believe families deserve transparent, timely, and science-based information as more is learned.”
“MDA is seeking additional information, reviewing the available scientific and safety data with clinical and research experts, and has reached out to Novartis,” the association added. “We recognize the sense of urgency from families to access additional information about these reports in order to make informed treatment and monitoring decisions. MDA is working to learn more as soon as possible.”
‘Confidential channels’
SMA Europe, an umbrella organization for SMA patient groups across the continent, issued its own statement Thursday saying it was informed about the tumor cases “through confidential channels, and have made clear to Novartis that the SMA community now needs timely public communication.”
“We have strongly urged the company to provide clear information on what is currently known, what remains uncertain, what this may mean for people who have already received treatment, and whether any additional monitoring or action is recommended,” SMA Europe added.
SMA Europe and MDA spoke out after a hospice chaplain shared on LinkedIn the post of a private Facebook group in which the parent of a child with SMA wrote of being informed by his neurologist that Novartis was withholding information about some of the tumor cases and opting instead for a “tiered rollout” of data.
“I am also sending this screenshot to reporters. I strongly encourage you to abandon any belief that Novartis can control this narrative, and to do something radical for your company: tell the truth,” Rev. Carolyn Philstrom urged.
During the first three quarters of this year, Novartis’ Zolgensma Group—consisting of the namesake IV-formulation gene therapy and an intrathecal formulation approved last year and marketed as Itvisma® (onasemnogene abeparvovec-brve)—generated $1.071 billion in net sales, up 16% from $925 million in January–September 2025. Of that total, $404 million was generated during the third quarter, up 34% from $301 million in Q3 2025.
Zolgensma Group finished last year with $1.232 billion in net sales, up 1.5% from $1.214 billion in 2024. Zolgensma is one of Novartis’ top 20 brands.
Novartis shares traded on the SIX Swiss exchange barely budged, dipping 0.1% to CHF 134.12 ($163.25) on Thursday. Novartis’ American Depositary Receipts, traded on the New York Stock Exchange, slid 1.85% to $161.93.
Past safety issues
The nine acknowledged tumors are not the first instances of safety issues tied to Zolgensma.
In 2022, Novartis acknowledged that two patients died of acute liver failure following treatment with Zolgensma. Both cases occurred at approximately five to six weeks post Zolgensma infusion, and approximately 1-10 days following the initiation of corticosteroid taper, Novartis stated at the time.
In response, Novartis revised Zolgensma’s label to specify that fatal acute liver failure had been reported. That marked a change from the previous wording of the gene therapy’s “black box” warning, which previously included acute liver failure as a known side effect that has been reported following treatment.
Zolgensma was developed by AveXis, a gene therapy developer that was acquired by Novartis for $8.7 billion in a deal completed in 2018.
A year later, the FDA approved Zolgensma for the treatment of SMA in children under age two with SMA with bi-allelic mutations in the SMN1 gene. Zolgensma was the second gene therapy authorized by the FDA for an inherited disease.
Later in 2019, the FDA announced AveXis’ acknowledgement that the accuracy of data from product testing performed in animals submitted in its Biologics License Application (BLA) for Zolgensma had been impacted by an unspecified manipulation of data intended to support the development of its production process for the gene therapy. AveXis replaced its two top scientific executives, one of whom publicly denied wrongdoing.
A 2020 paper published in The Journal of Pediatrics detailed two cases of transient, drug-induced subacute liver failure following treatment with Zolgensma.
And a 2021 study in Nature-published Gene Therapy showed that of nine children treated with the gene therapy in Qatar, none experienced failure—but all patients experienced elevated levels of the liver enzymes aspartate aminotransferase (AST) or alanine transaminase (ALT), two experienced high prothrombin time, and one experienced elevated bilirubin. One patient experienced vomiting after infusion.
Beyond Zolgensma
Zolgensma isn’t the only gene therapy linked to tumors this year.
In January, Regenxbio announced that the FDA placed a clinical hold on its AAV9 gene therapy candidate RGX-111 for the treatment of mucopolysaccharidosis type I (MPS I or Hurler syndrome) after a single case where an intraventricular CNS tumor developed in a 5-year-old boy treated in its Phase I/II trial (NCT03580083). The FDA also placed a clinical hold on a similar gene therapy RGX-121 for the treatment of MPS II (Hunter Syndrome), citing the similarities in products, study populations, and shared risk between the clinical studies. The clinical holds remain in effect.
“The tumor was successfully resected, and the patient remains in neurologically stable condition with advanced cognitive function at five years of age—an outcome that is inconsistent with the natural history of severe MPSI,” the study’s corresponding author, Lindsey A. George, MD, of the Perelman Center for Cellular and Molecular Therapeutics at Children’s Hospital of Philadelphia, reported in May in The New England Journal of Medicine (NEJM).
“Data from three decades of experience with more than 6000 patients have shown that AAV gene therapy is associated with a favorable safety profile1 and clinical benefits among diverse patient populations,” George and colleagues commented. “That said, our findings support the hypothesis that rare AAV integration can contribute to human oncogenesis, which emphasizes the need to optimize gene delivery methods and monitor transduced tissues after treatment.”
And in October, Michigan-based researchers led by Arul M. Chinnaiyan, MD, PhD, of the Michigan Center for Translational Pathology reported in The New England Journal of Medicine a case of paraspinal neoplasm in a 3-year-old boy with infantile-onset Krabbe disease (with biallelic GALC variants p.Arg220Ter and p.Tyr319Cys) following treatment with Forbes biologics’ AAV gene therapy FBX-101.
“At the time of the last follow-up, the patient remained asymptomatic,” Chinnaiyan and colleagues wrote. “These findings emphasize the need for cassette designs without splice donors, as well as attention to vector purity and extended genomic surveillance after AAV gene therapy.”
And in October, Michigan-based researchers led by Arul M. Chinnaiyan, MD, PhD, of the Michigan Center for Translational Pathology reported in The New England Journal of Medicine a case of paraspinal neoplasm in a 3-year-old boy with infantile-onset Krabbe disease (with biallelic GALC variants p.Arg220Ter and p.Tyr319Cys) following treatment with Forbes biologics’ AAV gene therapy FBX-101.
“At the time of the last follow-up, the patient remained asymptomatic,” Chinnaiyan and colleagues wrote. “These findings emphasize the need for cassette designs without splice donors, as well as attention to vector purity and extended genomic surveillance after AAV gene therapy.”
