FDA Probes Whether Novartis Gene Therapy Zolgensma Spurs Tumors in Kids

The FDA has opened an investigation into Zolgensma, Novartis's gene therapy for spinal muscular atrophy, after two children who received it developed tumors that showed evidence of being tied to the treatment. Novartis disclosed the cases on Friday. Since Zolgensma won approval in 2019, the company has logged nine reports of tumors in treated patients, according to emjreviews.com.

The biology points at a specific spot in the genome. In both pediatric cases, some of the delivered genetic material had slotted into the patient's DNA near or inside GLI1, a gene that governs cell growth and can fuel cancer when it runs too hot. The therapy carries a promoter — an on-switch meant to activate its own gene — and researchers found it sitting where it could abnormally fire up GLI1, a possible link to the tumors.

The agency isn't pulling the drug. It said the benefits of Zolgensma and of Itvisma, Novartis's related therapy, still outweigh the risks of their approved use while the review continues, and that it is weighing whether regulatory action is warranted. Zolgensma is infused intravenously and cleared only for patients under two; Itvisma is injected into spinal fluid and used in adults and children over two. Both rely on a modified AAV virus to ferry a working gene into cells.

Patient groups aren't waiting for answers. SMA Europe said the news, confirmed to it through confidential channels, is concerning for families whose children have already been treated or are weighing it, and urged Novartis to spell out what's known, what's uncertain and whether extra monitoring is needed. Cure SMA and the Muscular Dystrophy Association in the US have contacted the company and are consulting experts on when the tumors developed, whether treatment caused them and what follow-up patients need.

Novartis pushed back on any suggestion it sat on the information, saying it notified health authorities in a timely and appropriate manner in both cases and that the potential tumor risk already appears in Zolgensma's prescribing information. The company did not say where the two new cases occurred. More than 6,000 children have received the one-time therapy.