Advocates are sounding the alarm on social media as they learn from their doctors that Novartis has received reports of tumors in patients who have been treated with the spinal muscular atrophy gene therapy.
Novartis’ Zolgensma has faced its share of controversy. Now, the spinal muscular atrophy gene therapy is making the rounds on social media again, as patient advocates sound the alarm over tumors possibly related to the product.
“Just wanted to give people a heads-up, just got back from a neurologist appointment where we were informed that Zolgensma has been linked to two cases of kids developing tumors with seven more cases that are likely tied to it,” Dustin Brondyke, who said he has a child with spinal muscular atrophy (SMA), wrote Wednesday on LinkedIn in a post shared by patient advocate Carolyn Philstrom. “Novartis, the pharmaceutical company is withholding information on some of the cases and is doing a ‘tiered rollout’ of information instead of publishing the findings,” Brondyke added.
In communications shared with BioSpace by Philstrom on Thursday morning, another parent of a child with SMA “came to know about this tumor issue last week.” The patient’s appointment was Nov. 4. “It seems Novartis has written to everyone at the same time,” the anonymous parent wrote. “So far, the two confirmed cases seems to have happened 18-60 months after dosing.”
Since Zolgensma was approved in 2019 for children under two years old with SMA, nine tumors have been reported in patients previously treated with the therapy, Novartis confirmed with BioSpace in a Thursday morning statement.
“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,” the spokesperson said. “The potential risk of tumors due to vector integration is currently included in the Zolgensma prescribing information.”
Indeed, Zolgensma’s label includes a warning about the theoretical risk of tumorigenicity stemming from the gene therapy’s adeno-associated viral (AAV) vector. Seven reports of tumors have not been causally linked to the therapy.
As of Thursday, more than 6,000 patients have been treated with Zolgensma across clinical trials, managed access programs and commercial treatment, Novartis said in its email. “As part of Novartis’ ongoing commitment to monitoring the safety of our medicines, we continually evaluate new safety information and assess all reported cases.”
SMA Europe acknowledged the reports in a statement published Thursday morning.
“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,” the organization said. “SMA Europe has also been informed about the situation through confidential channels and have made clear to Novartis that the SMA community now needs timely public communication.”
Zolgensma uses an AAV vector to deliver a transgene encoding the human survival motor neuron (SMN) protein, which is essential for motor neuron function. SMA is caused by a mutation or deletion in the SMN1 gene.
This is not the first time Zolgensma has come under the microscope for safety concerns. The focus of previous scrutiny, however, had focused on liver-related adverse events. In September 2021, two years after Zolgensma’s approval, an FDA advisory committee was held to discuss both Novartis’ therapy and Spark Therapeutics’ Luxturna, a gene therapy for an inherited retinal disease.
About one-third of the 500 patients who had received Zolgensma at that time had experienced a liver-related adverse event, including one case of serious liver failure, according to FDA documents published at the time, Fierce Biotech reported. A summary of the adcomm meeting concluded that “Benefit-risk evaluations of AAV gene therapy (GT) products should be made on a case-by-case basis.”
The reports of tumors among patients who received Zolgensma come as Novartis is already dealing with safety concerns over its investigational CAR T therapy rapcabtagene autoleucel (rap-cel). Late this summer, it was revealed that the company had paused multiple studies of zola-cel after three patients who received the therapy died from immune effector cell-associated hemophagocytic syndrome.
Clarification (Nov. 5): BioSpace has edited the headline to most clearly reflect that a causal link has not been made in all nine cases.
