Evaluating Spinal Muscular Atrophy Gene Therapy Zolgensma in Heavier and Older Patients


Sandra P. Reyna, MD, the chief scientific advisor and head of global medical engagement for SMA at Novartis, discussed data from the phase 3b SMART clinical trial (NCT04851873) that were presented at MDA's 2024 conference.

Sandra P. Reyna, MD, the chief scientific advisor and head of global medical engagement for SMA at Novartis

Sandra P. Reyna, MD

Data from the phase 3b SMART clinical trial (NCT04851873), which evaluated marketed adeno-associated virus vector (AAV)-based gene therapy nasemnogene abeparvovec (Zolgensma; Novartis) in patients with spinal muscular atrophy (SMA), showed evidence of clinical benefit in patients heavier and older than those treated in previous clinical trials. These results were recently presented in a poster at the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 3-6, in Orlando, Florida.

Shortly after the conference, CGTLive® reached out to Sandra P. Reyna, MD, the chief scientific advisor and head of global medical engagement for SMA at Novartis, to learn more. Reyna discussed the broader context of these findings and the key implications, as well as areas of interest for further study.

CGTLive: Can you give some background info about Zolgensma’s current place in the landscape of care for SMA and the relevance of patient age and weight to its established safety/efficacy profile?

Sandra P. Reyna, MD: Zolgensma is unique in that it’s the only one-time gene therapy treatment for SMA. It replaces the function of the missing or nonworking SMN1 gene, treating the genetic root cause of the disease. in the US, Zolgensma is FDA-approved to treat patients under the age of 2, but many other countries have broader indications, which are not based on age but are guided by weight recommendations.

What were the key findings from this new research on Zolgensma in older and heavier patients that was presented at MDA’s 2024 conference?

Historically, Zolgensma clinical trials have only included treatment-naïve patients under the age of 2. In contrast, the SMART study enrolled patients weighing 8.5 to 21 kg, regardless of age, with the eldest participant aged just over 9 years old at the time of dosing. The mean age was around 4.6 years old. Notably, 21 of 24 patients had previously received either nusinersen or risdiplam, while the other 3 were treatment-naïve. No new safety signals were observed in the study and most patients maintained motor milestones observed at baseline at the end of the 1-year study. The results provide evidence that Zolgensma is clinically beneficial for older and heavier patients with SMA.

What would you say are the main implications that doctors and the broader healthcare community should take away from these findings?

The results from the SMART study supplement a growing body of evidence on the use of Zolgensma in this older and heavier population. This data should build confidence among caregivers and healthcare professionals as they make informed treatment decisions for the studied population.

Are there any limitations of the data or areas of interest for further research in this space?

SMART assessed Zolgensma’s impact on a specific set of patients that are older and heavier than those previously studied in Zolgensma intravenous (IV) clinical studies. In addition to our IV treatment, we are also investigating the use of an intrathecal formulation of gene therapy in ages 2 to 18. Novartis is committed to reimagining possibilities for those with SMA, including in patients with later-onset SMA.

Is there anything else you would like to share with our audience?

The takeaway from this trial is that Zolgensma is clinically beneficial to those with SMA who are older, heavier, and those who have been previously treated. Treatment makes all the difference in a child and family’s journey. Knowing this, we continue to explore safety and efficacy in more diverse patient groups, and we continue to look for opportunities to reimagine possibilities for the SMA community.

This transcript has been edited for clarity.

1. McMillan H, Baranello G, Farrar M, et al. Safety and efficacy of intravenous onasemnogene abeparvovec in pediatric patients with spinal muscular atrophy: findings from the phase 3b SMART study. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6; Orlando, FL. Poster #S110
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