The US Food and Drug Administration (FDA) has launched an investigation into a Novartis gene therapy for potential links to tumour growth in patients.
The Swiss drug maker disclosed on Friday that two children who had received Zolgensma (onasemnogene abeparvovec), a spinal muscular atrophy treatment for patients under two years old, had developed tumours which showed evidence of being linked to the drug.
Novartis said that overall, it had received nine reports of tumours in patients who have been treated with Zolgensma since it was first approved in 2019.
Zolgensma is one of two separate gene therapies for the treatment of spinal muscular atrophy developed by Novartis, and is administered via intravenous infusion exclusively in patients below the age of two.
The other, Itvisma (onasemnogene abeparvovec-brve), is given via intrathecal injection into the spinal fluid, and is used in adults and children over the age of two.
Both drugs work by delivering a working gene into a patient’s cells using a modified virus called AAV as a delivery vehicle. The treatment is intended to help cells make a protein that people with spinal muscular atrophy lack.
Typically, the delivered genetic material stays separate from the patient’s own DNA. However, in the two cases where children presented with tumours, some of the material had become inserted into the patient’s DNA, near or inside a gene called GLI1, the FDA reported.
The GLI1 gene helps control cell growth and if it becomes too active, can contribute to cancer growth.
The treatment’s genetic material includes a “promoter” or on-switch that prompts cells to activate a certain gene.
Researchers found that the switch was inserted in a position where it could abnormally activate GLI1, helping drive tumour growth, pointing to a possible link between the therapy and the tumours.
The FDA said, however, that while investigations are ongoing, the benefits of both Zolgensma and Itvisma continue to outweigh the potential risks of their approved use.
The agency also announced that it is considering whether regulatory action is appropriate considering the risk.
These findings follow complaints from patient advocacy groups that Novartis was slow to share information about the cases and have since not provided all relevant details.
SMA Europe, an umbrella organisation of spinal muscular atrophy (SMA) patient organisations across Europe, released a statement on the matter ahead of the FDA’S announcement following reports on social media.
It acknowledged that the news, which had been confirmed to it through “confidential channels”, is “concerning” for families of children who have already received the treatment or are considering going forward with it
The statement followed as: “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.”
Cure SMA and the Muscular Dystrophy Association in the US, have contacted Novartis and are consulting experts to obtain answers for families.
Their questions include when the tumours developed, whether treatment caused them and what follow-up patients may need
Novartis said in a statement that it had notified health authorities of the risk in a timely and appropriate manner in both cases and that the potential risk of tumours is included in Zolgensma’s prescribing information.
The one-time therapy has been administered to over 6000 children. Novartis did not provide details on where the two new cases were in its statement.
Featured image: Michael Derrer Fuchs on AdobeStock
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