Medicines agency examines: Suspicion of tumor formation in children due to gene therapy

Silver Spring/USA. A few years ago, Zolgensma was the most expensive drug in the world with a price of around two million euros. The US Food and Drug Administration (FDA) says it is currently investigating reports of cancer in several children who were treated with this therapy. The gene therapy from Novartis, which will be approved in the USA and Europe for children under the age of two from around 2020, is aimed at the so-called spinal muscular atrophy (SMA). This rare hereditary disease causes, among other things, muscle wasting and often leads to death before the child reaches the age of two.

Zolgensma is designed to target the genetic cause of spinal muscular atrophy by using a single intravenous infusion to replace the function of the missing or non-functioning SMN1 gene. Modified viruses - so-called AAV vectors - are supposed to act as gene ferries and introduce a healthy copy of this gene into the body's cells.

Maybe this is where the problem lies. According to FDA information, tumors that appeared after therapy affected the central and peripheral nervous system, the spinal area and the kidney. The oncogene GLI1, which can contribute to the development of cancer, is involved in three cases. In two of them, analyzes discovered DNA from the virus used in the therapy in the tumor tissue; the third case is still being examined, it said.

Such viruses are also used as gene ferries in other gene therapies. The Medicines Agency explicitly refers to two specialist reports on cancer cases in the context of other comparable treatments. “The FDA is closely monitoring the risk of neoplasia, including malignancies, in other similar AAV vector-based gene therapy programs,” it said. Whether regulatory measures are necessary is being examined. Overall, however, the benefits of therapy with Zolgensma exceed the possible risks, the authority writes.

The patient organization SMA Europe quotes from a letter from Novartis that more than 6,000 patients have been treated with Zolgensma since 2019. The company received a total of nine reports of tumors in patients treated in this way. The two affected people, whose genetic material was integrated with vector DNA, have been treated and are continuing to be monitored, it said. The company emphasizes that it points out the potential risk of tumors due to vector integration in the specialist information.