Evelina-led study published into real-world use of Zolgensma

A study led by Evelina London Children's Hospital and published in the latest issue of The Lancet Regional Health - Europe, provides important information about Zolgensma's use in real-world clinical settings for children with type 1 Spinal Muscular Atrophy (SMA).

SMA affects a group of nerve cells that run from the spinal cord to the muscles. They carry messages to the muscles needed to move our arms, hands, head and neck so we can roll, sit, crawl and walk. They also carry messages to the muscles we use to breathe and swallow. The condition is caused by a fault (mutation) in a gene called survival motor neuron 1 (SMN1).

Zolgensma, or onasemnogene abeparvovec, is a licensed gene therapy that replaces the faulty gene with a new copy. It can allow babies and young children with SMA type 1 to reach motor milestones such as sitting and crawling, to breathe without a ventilator, and to live for longer. Evelina London is 1 of 6 centres across the UK that can treat babies and young children with SMA type 1 with Zolgensma.

Since Zolgensma was introduced into clinical practice in 2019, evidence has been published about its use in real world settings for children younger than 2 years old and weighing less than 13.5kg. However, there was a lack of information on its use in older, heavier patients.

To address this information gap, clinicians at Evelina London studied data from 99 patients with genetically confirmed SMA type 1 treated with Zolgensma at the 6 UK centres between May 2021 and January 2023. As the patients treated included patients over 2 years old and weighing more than 13.5kg, it was possible to observe the treatment's impact on symptoms, how safe it is to use and to get a better understanding of steroid use in this group of patients.

Dr Vasantha Gowda, consultant paediatric neurologist at Evelina London and the study's lead author, said: "It is really important to continue to study the real-world experience of delivering Advanced Therapy Medicinal Products as this will help address the gaps in the data regarding the safety and efficacy of these transformative medications in wider groups of patients. Gene therapies are an evolving technology and we need to continue to collate data to further our knowledge regarding long-term efficacy and safety."

This study was only possible thanks to the support of neuromuscular colleagues from other UK centres and I'd like to thank all our collaborators. By studying the available data across the UK patient population, we have increased our understanding of its use in a group of patients for whom real-world data was previously lacking. The findings will help inform clinical practice and help clinical teams provide more accurate information about potential benefits and risks to families to aid decision-making around treatment options.

7-year-old Reyansh was treated with Zolgensma at an older age and heavier weight than most children with SMA type 1. He was 5 and weighed 14.2kg when he received the treatment in September 2022.

Reyansh has been a regular patient at Evelina London throughout his life. He was immediately transferred to the hospital as a newborn baby after a stroke at birth. He remained weak after going home, and this was thought to be due to his stroke. However, when Reyansh's movements had not improved, doctors suspected SMA. Genetic tests carried out at the hospital confirmed he has the condition.

The Evelina London team gave Reyansh's parents, Prashant and Sarada, lots of information, such as how Reyansh's movement and speech would probably be affected and the likely course of his condition.

Prashant and Sarada explained:

Dr Gowda and the neuromuscular team have been fantastic from the start, giving us the information we need, answering our questions and supporting us through all of Reyansh's appointments and treatments. 

"Reyansh was initially treated with nusinersen, another available treatment for SMA. But this requires regular injections. As Reyansh got older, he started to get more anxious and resistant about coming into hospital every few months for an injection."

Prashant and Sarada initially discussed the possibility of Reyansh being treated with Zolgensma with Dr Gowda and the team in March 2022 and he received the one-off treatment in September 2022.

They continued: "The team were great at explaining everything to us. They were clear that at 5 years old, Reyansh was older than most children who had received Zolgensma treatment and that there could be additional risks. They reassured us that he'd be closely monitored. We weighed up the options and decided to go for it."

At the time of receiving the one-off gene therapy treatment, Reyansh spent 4 days in hospital. He was given steroids which were important to minimise the side effects from the gene therapy and returned to the hospital every few days for blood tests. It was through the frequent blood tests that some abnormality of liver enzymes caused by the gene therapy were detected and successfully treated.

Prashant and Sarada have seen improvements in Reyansh's SMA since receiving Zolgensma. They explained:

Since receiving Zolgensma, Reyansh's arm strength has definitely gone up. He is more confident about doing things on his own, such as helping with tidying, moving something from one point to another, helping while shopping and adjusting himself so he's comfortable in bed. His speech has improved too. He can tell us what happened at school and is better at telling us what he needs.

"He is also keen to try to eat more food by mouth and got better at using the spoon himself, having been previously fed via a tube. He wants to participate in things more, and is less anxious, although like a lot of young children he doesn't like being told what to do when he has to do his physio exercises!"

"As parents you want to make the right decisions for your child, and you want to base these on having the best available information available to you. It's great to know that the findings from the analysis carried out by Dr Gowda and her team, which included information about the impact of the treatment on older children like Reyansh, will be useful to clinical teams across the world and help other families with their decision-making in future. It's also so important to us as a family that Reyansh is under the care of a specialist children's hospital where he can get the expert support he needs from various different teams."