ZURICH, November 08 (AJP) -A U.S. investigation into tumors linked to Zolgensma is raising questions about long-term monitoring for children in South Korea and worldwide who received the one-time gene therapy for a potentially fatal muscle-wasting disease.
The findings also have implications for other treatments using similar technology. The U.S. Food and Drug Administration (FDA) said Friday it was reviewing whether stronger warnings or other regulatory action were needed, while maintaining that the benefits of Zolgensma and the related treatment Itvisma outweigh their potential risks for approved uses.
For Korea, the findings put the focus on how children are followed after treatment and how emerging risks are explained to families. National health insurance has covered Zolgensma since August 2022, opening access to a treatment previously beyond the financial reach of most households.
At the time, authorities set its reimbursed price at about 1.98 billion won per dose and said eligible patients would pay no more than 5.98 million won under the applicable out-of-pocket ceiling. Those figures describe the coverage terms announced in 2022.
Korea’s monitoring requirements extend beyond the five-year treatment-response assessments associated with insurance coverage. When the Ministry of Food and Drug Safety approved Zolgensma in 2021, it designated the medicine for 15 years of follow-up for adverse events. The distinction matters: assessing whether a treatment works and tracking delayed safety problems serve different purposes.
Made by Swiss drugmaker Novartis, Zolgensma treats spinal muscular atrophy (SMA), an inherited condition that destroys the nerve cells controlling muscles. Severe cases can rob babies of the ability to move, swallow and breathe.
The therapy uses a modified viral carrier to deliver a functioning copy of the SMN1 gene. In the United States, it is administered as a single intravenous infusion to eligible children under two.
Novartis said it had received nine reports of tumors among patients treated since the drug’s first approval in 2019. More than 6,000 patients have received Zolgensma through trials, access programs and commercial treatment. The reports do not establish that the medicine caused all nine tumors or provide a reliable measure of an individual patient’s risk.
The FDA identified two cases in which the treatment’s viral DNA had inserted into the patients’ genome near or within GLI1, a gene capable of driving cancer. A third GLI1-associated case remains under investigation.
The agency also said the risk applies to Itvisma because it uses the same viral carrier and genetic construct, although no tumors had been reported following that treatment. Itvisma is approved in the United States for patients aged two and older.
The FDA is examining whether existing product warnings and follow-up studies adequately address the findings. It is also monitoring similar gene therapy programs, widening the implications beyond Novartis’s SMA treatments.
For families, a central issue is what should change in their children’s care. In a November 4 update, England’s specialist Zolgensma team said the information then available did not warrant additional scans, tests or changes to routine follow-up. The FDA subsequently advised monitoring treated patients for tumor formation. These statements came from different authorities and do not establish a new Korean screening protocol.
SMA Europe has urged Novartis to explain clearly what is known, what remains uncertain and whether additional monitoring is needed. Novartis said it had notified health authorities promptly and appropriately and was working with them on next steps.
AJP Takeaways
- The US Food and Drug Administration said on Friday it is investigating a “serious risk” of cancer linked to Zolgensma, Novartis’s one-time gene therapy for spinal muscular atrophy.
- Novartis said it has received nine tumor reports in patients treated with Zolgensma since 2019, two of which showed evidence of a link to the gene therapy.
- Zolgensma has been covered by South Korea’s national health insurance since August 2022, with Korean families required to agree to five years of follow-up checks.
- Tags: Novartis, Zolgensma, Itvisma, US Food and Drug Administration, FDA, spinal muscular atrophy, gene therapy, GLI1, SMA Europe, Ministry of Food and Drug Safety, European Medicines Agency, Swissmedic, South Korea, national health insurance, Switzerland
Copyright ⓒ Aju Press All rights reserved.