Novartis Phase III trial of onasemnogene abeparvovec achieves primary goal in SMA patients

On December 30, 2024, in Basel, Switzerland, Novartis announced promising results from its Phase III STEER study. This pivotal research evaluated the efficacy and safety of intrathecal onasemnogene abeparvovec, known as OAV101 IT, an investigational therapy for patients with Spinal Muscular Atrophy (SMA) Type 2. The study focused on treatment-naïve patients aged between two and 18 years who can sit but have never walked independently.

The STEER study primarily aimed to assess improvements in motor function using the Hammersmith Functional Motor Scale – Expanded (HFMSE). This scale is a standard measure for evaluating motor abilities and disease progression specifically in SMA patients. OAV101 IT was compared against a sham control, which is a simulated procedure without delivering the actual treatment. Results showed a significant increase in HFMSE scores in patients treated with OAV101 IT compared to those who received the sham control, indicating enhanced motor function in the treated group.

In terms of safety, the trial revealed a favorable profile for OAV101 IT. The incidence of adverse events was comparable between the treatment and control arms. The most frequently reported adverse events included upper respiratory tract infections, fever, and vomiting. These safety findings support the potential of OAV101 IT as a viable treatment option for SMA.

Novartis intends to present these results to regulatory bodies such as the US Food and Drug Administration (FDA) in 2025. The company aims to make OAV101 IT accessible to SMA patients who are in need of effective treatment. Additionally, the detailed data from this study will be showcased at a medical conference scheduled for 2025.

Dr. Shreeram Aradhye, President of Development and Chief Medical Officer at Novartis, highlighted the significance of the STEER trial’s outcomes. He emphasized the trial's demonstration of the efficacy, safety, and tolerability of OAV101 IT for SMA patients aged two and older, showcasing a positive risk-benefit profile. Dr. Aradhye reiterated Novartis's commitment to innovating SMA treatments through their gene therapies designed to restore the function of the SMN1 gene.

Dr. Crystal Proud, a pediatric neurologist and principal investigator involved in the study, underscored the importance of maintaining motor function for older SMA patients. The treatment's ability to not only maintain but also improve motor function was seen as a substantial advantage, potentially enhancing patients' independence in daily activities.

The STEER study builds upon previous findings from the Phase I/II STRONG study, which showed meaningful improvements in HFMSE scores in younger patients with SMA Type 2. Overall, the results from these studies contribute to the growing body of evidence supporting the use of one-time gene therapies for treating SMA.

The Phase III STEER study was a comprehensive, randomized, double-blind, sham-controlled investigation involving over 100 patients. Participants were assigned either to receive OAV101 IT or undergo a sham procedure. At the conclusion of a 52-week period, eligible patients had the opportunity to receive the alternative treatment they did not initially receive, ensuring all participants had access to the potential benefits of OAV101 IT.

OAV101 IT's development is part of a broader clinical program that includes multiple studies evaluating its safety and efficacy across various patient groups and settings. As part of its extensive research portfolio, Novartis has collaborated with several institutions worldwide to harness gene therapy technologies aimed at addressing SMA and improving patient outcomes.