A world-leading research program has seen the Sydney Children’s Hospital, Randwick, be the first hospital globally to deliver a cutting-edge gene therapy for children up to six years old with spinal muscular atrophy (SMA).

SMA is a rare genetic disease causing progressive muscle weakness. Without intervention, the most severe types of SMA can have a life expectancy of less than 2 years old.

The international clinical trial, dubbed the SMART trial, investigated the safety and efficacy of gene therapy, Zolgensma®, in a cohort of 24 young children, ranging from nine months to six years old and weighing between 8.5 and 21 kg. These children had varying severities of SMA symptoms, with many already undergoing other treatments.

The trial builds on the success of the SPR1NT trial, which led to Zolgensma® being listed on the Pharmaceutical Benefits Scheme (PBS) for use in eligible infants under nine months old with SMA who have specific gene variations. Unlike other treatments that require daily administration, the life-changing treatment is a one-time injection that delivers the missing gene causing SMA. 

Thanks to the outstanding work by the Kids Advanced Therapeutics (KAT) program, the Sydney Children’s Hospital, Randwick, was successful in being chosen as a study site for the SMART trial and was the first site globally to dose its participants.

KAT’s role is to navigate complex regulatory procedures, handle feasibility assessments, submitting budgets, support governance and ethics approvals to streamline processes for innovative clinical trials.

Study co-lead, Professor Michelle Farrar, praised the KAT program for expediting the SMART trial through the hospital. 

“Without the support of KAT, it would have taken twice as long to start-up the study. Instead, we had a dedicated project officer from the KAT team who communicated with the sponsor and advocated for us to be a site for the study. They also helped us with the study start-up processes,” Professor Farrar said.

“This support made us the first site to be study-ready and because of this, were the first in the international study to dose a patient, and meant we were able to get outcomes for the patients who come to our hospital.”

The findings from the SMART trial, published in the prestigious journal Neurology, have been revolutionary in helping gather evidence to expand the use of the gene therapy for other cohorts of young children diagnosed with SMA. 

“The results of the study were positive with all participants reaching a stable disease trajectory.”

“The study also provided us with an understanding of tolerability in this population and enabled tailored information to be provided based on characteristics of the child.” 

The SMART trial is one example of how research enabling programs like KAT are helping accelerate novel research and enable access to innovative therapies across the Sydney Children’s Hospitals Network, ensuring children receive the best possible care.

The KAT program is operated through Kids Research, the research arm for the Sydney Children’s Hospitals Network, and is kindly supported by Luminesce Alliance and Sydney Children’s Hospitals Foundation.

Prof Farrar leads the Paediatric Neurology Research Group, an affiliated group with the University of NSW School of Clinical Medicine working within the Department of Neurology based at the Sydney Children’s Hospital, Randwick.