John Day, PhD, MD, Director of Neuromuscular Medicine at Stanford University, discusses the development of Itvisma gene therapy for patients with spinal muscular atrophy (SMA).
SMA is a group of genetic neuromuscular disorders that affect the motor neurons, causing progressive muscle weakness and loss of movement. Many types of SMA affect the muscles involved in walking, sitting, arm movement, and head control. Breathing and swallowing may also become difficult as the disease progresses. SMA types 1, 2, 3, and 4 are caused by mutations in the SMN1 gene. Extra copies of the nearby related gene, SMN2, modify the severity of SMA. There are other rarer types of SMA caused by changes in different genes.
In the last decade, gene therapy for SMA has evolved significantly. In 2017, an intravenous adeno-associated virus (AAV) vector-based gene therapy, Zolgensma (onasemnogene abeparvovec), was developed. Later approved in 2019, the therapy was indicated for patients less than 2 years of age with SMA due to weight-based dosing limitations. As Dr. Day explains, the treatment’s intravenous administration and large viral load caused concerns on reactions and side effects.
To address these limitations, researchers began the development of a new administration route, an intrathecal injection (i.e., injection into the spinal column). Dr. Day explains how this allows for a more targeted approach that can be dosed in lower amounts, thus decreasing concerns regarding adverse reactions.
Itvisma (onasemnogene abeparvovec), approved in November 2025, is a one-time intrathecal injection for patients with SMA. It is the first gene therapy licensed to be given via spinal injection, which Dr. Day believes may change the landscape for other genetic central nervous system disorders.
The approval of Itvisma was based on data from the registrational phase 3 STEER clinical trial and supported by the open-label phase 3b STRENGTH study. Itvisma was observed to significantly improve motor function and stabilization of motor abilities typically not seen in the natural history of the disease, with effects sustained over 52 weeks of follow-up. Additionally, the safety profile of Itvisma was consistent across both studies. The most common adverse events in the STEER study were upper respiratory tract infection and pyrexia, and the most common adverse events in the STRENGTH study were common cold, pyrexia, and vomiting.
For more information, visit https://www.itvisma-hcp.com
To learn more about SMA, visit https://checkrare.com/sma-in-focus-practical-insights-from-mda-2026/