STEER Data Open Door to SMA Gene Therapy for Wider Age Range of Children

Results from the phase 3 STEER study of intrathecal onasemnogene abeparvovec showed encouraging efficacy and safety data for children aged 2 to 17 years with spinal muscular atrophy (SMA), paving the way for much broader uptake of this disease-modifying gene therapy.¹ The findings were presented in a late-breaking research session of the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in Dallas, Texas, held March 16-19, 2025.

Onasemnogene abeparvovec (Zolgensma; Novartis) has been FDA approved since 2019 for patients younger than 2 years, in whom it is administered intravenously and has been shown to significantly extend lifespan and functioning.² But this indication leaves out those older than 2 years, who are currently limited to non–gene therapy options like nusinersen (Spinraza; Biogen) and risdiplam (Evrysdi; Genentech), and in whom the availability of a one-time gene therapy would be especially coveted for this degenerative neuromuscular disease that can cause young patients to quickly lose the ability to roll over, chew food, and brush their hair.

Seeking to expand the use of onasemnogene abeparvovec, researchers undertook the STEER study (NCT05089656), a phase 3, multicenter, multinational, randomized, double-blind trial of the efficacy of the gene therapy into the intrathecal space in the spinal canal.¹ Results were delivered today at the MDA meeting by Crystal Proud, MD, director of neurology and neuromuscular medicine at the Children's Hospital of the King's Daughters in Norfolk, Virginia.

Proud noted that participants had to be treatment naïve and to be able to sit independently, but they had never been ambulatory. Of the 136 participants, 126 received either this intervention (n = 75) or a sham procedure (n = 51). The participants ranged in age from 2.1 to 16.6 years, and the mean age at dosing was 5.88 years.

After 52 weeks, the study met its primary efficacy end point, with the treatment arm demonstrating a 2.39-point improvement in the Hammersmith Functional Motor Scale – Expanded (HFMSE) score vs 0.51 points in the sham arm (P = .0074). The HFMSE is a validated scale used to assess patients’ motor function, including motions like standing, crawling, and sitting; recent research suggests that a cutoff of 1.5 points may indicate meaningful improvement.³

Results could pave the way for much broader uptake of this disease-modifying gene therapy. | Image Credit: © Rochu_2008 - stock.adobe.com

Exploratory efficacy analyses in the subgroup 5 years and older also favored the treatment arm, with a 2.45-point treatment effect on HFMSE (P = .0193) and a 1.72-point on the Revised Upper Limb Module (P = .033).¹

Safety analyses revealed adverse event rates that were similar between the 2 arms; pneumonia and vomiting were the most prevalent serious adverse events in the treatment arm whereas pneumonia and lower respiratory infection were most common in the sham arm. “Peripheral sensory neuropathy presented in 2 cases, with symptoms managed with additional therapies, and improvements were seen over time,” Proud noted.

“The Hammersmith from an efficacy perspective demonstrated improvement of motor function in this very broad SMA patient population,” Proud concluded. “The primary end point was met with a mean difference of 1.88 points between the treatment and sham groups, and overall, the safety profile was favorable.”

The second period of STEER will involve the sham and treatment arms crossing over for an additional 12 weeks, after which the participants will be eligible to enroll in a long-term follow-up study.

If these results lead to a label expansion for onasemnogene abeparvovec to include children older than 2 years, payers will have to grapple with the implications of covering the high-priced gene therapy for a much larger pool of patients, and treatment centers will need to adjust their workflows and infrastructure to keep up with presumed demand.

References

1. Proud C, Wilmshurst JC, Sanmaneechai O, et al. Intrathecal onasemnogene abeparvovec for patients with spinal muscular atrophy: phase 3, randomized, sham-controlled, double-blind STEER study. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-18, 2025; Dallas, TX. Abstract LB450.

2. Rosenberg J. FDA approves gene therapy with $2.1M price tag for spinal muscular atrophy in pediatric patients. AJMC^®. May 24, 2019. Accessed March 19, 2025. https://www.ajmc.com/view/fda-approves-gene-therapy-with-21m-price-tag-for-spinal-muscular-atrophy-in-pediatric-patients

3. Coratti G, Bovis F, Pera MC, et al; ISMAC group. Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: an international study. Eur J Neurol. 2024;31(8):e16309. doi:10.1111/ene.16309