Novartis’ Zolgensma has faced its share of controversies. Now, gene therapy for spinal muscular atrophy is making the rounds on social media again, as patient advocates sound the alarm about tumors possibly linked to the product.
“I just wanted to warn people, I just got back from an appointment with a neurologist where we were informed that Zolgensma has been linked to two cases of children developing tumors and seven other cases that are likely linked to it,” Dustin Brondyke, who said he has a child with spinal muscular atrophy (SMA), wrote on LinkedIn in a post Wednesday. job shared by patient advocate Carolyn Philstrom. “Novartis, the pharmaceutical company, is withholding information about some cases and doing a ‘phased rollout’ of the information instead of publishing the results,” Brondyke added.
In communications shared with BioSpace by Philstrom Thursday morning, another parent of a child with SMA “learned about this tumor problem last week.” The patient’s appointment was November 4. “It appears Novartis wrote to everyone at once,” the anonymous parent wrote. “So far, the two confirmed cases appear to have occurred 18 to 60 months after administration.”
Since Zolgensma was approved In 2019, in children under two years of age with SMA, nine tumors were reported in patients previously treated with the therapy, Novartis confirmed with BioSpace in a statement Thursday morning.
“Of these, two cases to date have shown evidence of integration of the vector into patients’ DNA. In both cases, the patients have undergone treatment and continue to be monitored,” the spokesperson said. “The potential risk of tumors due to vector integration is currently included in the prescribing information for Zolgensma.”
Indeed, Zolgensma label includes a warning about the theoretical risk of tumorigenicity from the adeno-associated viral (AAV) vector of gene therapy. Seven reports of tumors were not causally related to treatment.
As of Thursday, more than 6,000 patients have been treated with Zolgensma in clinical trials, managed access programs and commercial treatments, 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 evaluate all reported cases.”
SMA Europe has taken note of these reports in a statement published Thursday morning.
“We understand that the relevant regulatory authorities are actively involved and are currently evaluating the available evidence and determining what additional measures may be necessary,” the organization said. “SMA Europe was also informed of the situation through confidential channels and made it clear to Novartis that the SMA community now requires 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 embarrassed.
This is not the first time that Zolgensma has been scrutinized for security reasons. However, previous studies have 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 a third of the 500 patients who had received Zolgensma at that time had experienced a liver-related adverse event, including one case of severe liver failure, according to FDA documents released at the time. Fierce biotechnology reported. A summary of the adcomm meeting concluded that “benefit-risk assessments of AAV gene therapy (GT) products should be carried out on a case-by-case basis.”
The reports of tumors among patients who received Zolgensma come as Novartis already faces safety concerns over its experimental CAR T treatment rapcabtagene autoleucel (rap-cel). At the end of summer it was revealed that the company had suspended several studies of zola-cel after three patients who received the treatment died from immune effector cell-associated hemophagocytic syndrome.
Novartis has suspended several studies of a CAR T candidate after three patients who received the treatment suffered fatal cases of immune effector cell-associated hemophagocytic syndrome. BMS, meanwhile, suspended some CAR T trials after separately observing “transient and reversible inflammatory events” with its therapy.
Clarification (November 5): BioSpace has amended the title to reflect as clearly as possible that a causal link has not been established in all nine cases.
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