Gene Therapy Shown to Improve Motor Ability for Children with SMA

Treatment with OAV101 IT (intrathecal onasemnogene abeparvovec; Novartis, Cambridge, MA) was associated with significant improvements in motor ability when administered to children with spinal muscular atrophy type 2 (SMA 2). Top-line results of the phase 3 STEER clinical study (NCT05089656) presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference suggest that 1-time injection of OAV101 IT into the spine may be safe and potentially effective as a treatment for SMA 2.

SMA 2 is caused by the loss of motor neurons due to reduced levels of the SMN protein resulting from the mutation or deletion of the SMN1 gene. OAV101 IT is a 1-time treatment that delivers a working copy of the SMN1 gene to cells via a genetically engineered adeno-associated virus serotype 9.

STEER was a double-blind, sham-controlled clinical study that included 126 treatment-naïve, sitting and never ambulatory participants aged 2 to <18 years with SMA 2 who were randomized to receive treatment with either OAV101 IT (n=75) or sham (n=51). The primary endpoint of the study was change from baseline to week 52 in total Hammersmith Functional Motor Scale–Expanded (HFMSE) score: a tool that measures ability in nonambulatory individuals with SMA 2.

Key results include the following:

• The primary endpoint of the study was met, with a mean improvement of 2.39 points in HFMSE score for OAV101 IT–treated participants vs a 0.51-point improvement for those who received sham.
• The most common adverse events (AEs) across both study groups were upper respiratory tract infection and pyrexia.
• Safety findings were consistent across groups in terms of overall incidence of AEs, serious AEs (SAEs), and AEs of special interest (AESIs).
• Pneumonia and vomiting were the most common SAEs for the OAV101 IT–treated participants.

“Many patients with SMA currently rely on chronic treatments to manage their disease,” said Shreeram Aradhye, President and Development and Chief Medical Officer at Novartis. “These positive top-line results from the STEER trial underscore the efficacy, safety and tolerability of OAV101 IT in patients with SMA aged 2 and above.”

According to a statement from the company, the results of STEER are consistent with findings from the phase 1/2 STRONG clinical study (NCT03381729).