Zolgensma Safe in Children with SMA Heavier than Clinical Trial Weights

In clinical trials evaluating Zolgensma for children with spinal muscular atrophy (SMA), the maximum weight of participants was 18.7 pounds. However, parents with children weighing over that weight might be concerned about the safety, efficacy, and tolerability for their children. According to SMA News Today, an analysis of data from the Global Managed Access Program highlighted that Zolgensma is safe for use in heavier children, with safety and tolerability consistent with that described in the initial trials. 

Interested in learning more? Take a look at the study findings published in Pediatric Neurology

What is Spinal Muscular Atrophy (SMA)?

Spinal muscular atrophy (SMA) is a rare genetic disorder caused by SMN1 gene mutations. These gene mutations cause the loss and degeneration of motor neurons in the brainstem and spinal cord. Normally, motor neurons transmit impulses from the spinal cord to the muscles. So, motor neurons degeneration causes muscle weakness and atrophy. Altogether, there are four types of SMA which differ in age of onset and symptom severity. Some common symptoms can include:

  • Developmental delays
  • Scoliosis
  • Difficulty swallowing, walking, crawling, sitting, or supporting the head
  • Tremors or muscle twitching
  • Muscle weakness
  • Limited mobility
  • Spontaneous tongue movements
  • Respiratory muscle weakness and difficulty breathing

Zolgensma and Clinical Studies

To begin, let’s look at what Zolgensma is. Developed by Novartis Therapeutics, Zolgensma is a 1-time, intravenous therapy designed for children aged 2 and younger with any form of SMA. Cure SMA describes Zolgensma as a: 

SMN-enhancing therapy that works by replacing the function of the missing or nonworking SMN1 gene with a new, working copy of an SMN gene. A virus, AAV9, carries the replacement gene into the body [and] ‘infects’ the cells with the new DNA.

Throughout different areas of the globe, Zolgensma is given to children weighing up to 46 pounds. However, clinical trial data only utilized children weighing up to 18.7 pounds, leaving a huge gap in the understanding of how the drug might affect heavier children. Currently, Novartis is exploring this in more depth through the Phase 3 SMART trial. 

However, in the meantime, researchers used data from the Global Managed Access Program to better understand the potential effects. Data was sourced from 102 children with SMA who weighed at least 18.7 pounds when they received their Zolgensma treatment. The findings showed that:

  • 53% of patients experienced adverse reactions such as fever, appetite loss, thrombocytopenia (low platelet counts), heightened liver enzymes, nausea, and vomiting. However, in a majority of patients, these were not serious reactions. 40% of those weighing 29.8-37.5 lbs. at the time of dosing also showed signs of liver toxicity, as did 45% of the overall group of patients. No patients experienced liver failure. 
  • 0.98% of patients experienced thrombotic microangiopathy, although the condition resolved itself within 4 weeks. 
  • No deaths reported were considered related to Zolgensma treatment. 

Although there were a number of potentially concerning reactions, these are in-line with safety and tolerability data from clinical trials.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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