Itvisma Gene Therapy for Patients With Spinal Muscular Atrophy

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 due to atrophy. Many types of SMA mainly affect the muscles involved in walking, sitting, arm movement, and head control. Breathing and swallowing may also become difficult as the disease progresses in many types of SMA. SMA type 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, there has been growing development in gene therapy for SMA. 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 spinal injection administration. Dr. Day explains how this allows for a more targeted approach that can be dosed in lower amounts, thus decreasing concerns on 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 highlights will 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. CHAPTERS Introduction 00:00 SMA Overview 00:25 Current Management 1:46 The Development of Itvisma Gene Therapy 2:38 Status of Nerves at Treatment 7:06 Advice to Newly Diagnosed Families 10:37 Take Home Message 13:00