• Zolgensma (onasemnogene abeparvovec-xioi), a treatment for children with spinal muscular atrophy (SMA), can sometimes lead to liver problems.
• The liver problems are usually mild, but in rare cases may be severe.
• Zolgensma’s label has been updated to indicate that when children with SMA take this treatment, they need to first undergo liver tests and should take corticosteroids before and after Zolgensma infusion.

New research suggests that Zolgensma — used to treat children with SMA — can cause liver damage and liver failure in rare instances. This revelation has prompted the U.S. Food and Drug Administration (FDA) to change the drug’s label to alert people about the potential side effects.

Zolgensma is a type of gene therapy that acts to correct the gene mutations that cause SMA. Zolgensma spurs neurons into making more SMN protein, which helps correct SMA symptoms like muscle weakness and breathing problems. A recent study found that children with SMA type 1 benefited from being treated with Evrysdi (risdiplam) after one-time treatment with Zolgensma

The FDA first approved Zolgensma in May 2019. This treatment, which is given as a one-time IV infusion, can be taken by children under 2 with SMA.

The FDA continues to monitor treatments after initially approving them to see whether they cause any side effects. The FDA recently updated Zolgensma’s label to include a boxed warning about potential liver problems. The warning states that the treatment can cause:

• Increased levels of liver enzymes, including aspartate aminotransferase, alanine aminotransferase, and bilirubin
• Liver damage
• Liver failure

How Does Zolgensma Affect the Liver?

These liver problems were reported in a recent study published by Novartis, the maker of Zolgensma. In this study, researchers collected data from 100 children who took part in Zolgensma clinical trials.

Tests showed that 90 out of 100 of the children had higher-than-normal levels of liver enzymes. In most cases, levels were increased only slightly. Additionally, 61 out of 100 children had increased liver enzymes before they were given Zolgensma, meaning that they may have had some preexisting liver problems before being treated.

For most children in Zolgensma clinical trials, liver enzyme levels returned to normal within two months. However, high enzyme levels can sometimes progress to worse liver problems. Out of 43 children treated with Zolgensma outside of clinical trials, two developed liver injury, which was successfully treated. One additional child was diagnosed with liver failure and required a liver transplant.

Ways To Prevent Liver Damage

Doctors usually administer corticosteroid medications, such as prednisolone, along with Zolgensma. Giving steroids before and after treatment can help prevent liver damage from the gene therapy.

Additionally, the new warning on the Zolgensma label recommends that doctors perform blood tests to examine how well the liver is working before giving the treatment. If a child has preexisting signs of liver damage, they may be more likely to experience liver-related side effects after taking Zolgensma. In some cases, doctors may recommend children with preexisting liver problems do not receive Zolgensma.