Gene therapy improves motor function in spinal muscular atrophy at 52 weeks
Key takeaways:
- Patients treated with onasemnogene abeparvovec recorded higher scores on all metrics vs. sham at 52 weeks.
- Onasemnogene abeparvovec demonstrated a favorable safety profile.
Intrathecal treatment with a vector-based gene therapy was associated with a greater improvement in motor function at 52 weeks compared with sham in patients aged 2 to 18 years with spinal muscular atrophy, data show.
The findings were presented at the Muscular Dystrophy Association Clinical & Scientific Conference.
“While many children and young adults with SMA receive chronic SMA therapies, there is still a critical unmet need for a single-administration therapy that helps halt functional decline and addresses the genetic root cause of the disease by providing a functional copy of the SMN1 gene,” Daniel Grant, vice president and global program head at Novartis, which funded the study, told Healio.
Crystal Proud, MD, a board-certified neurologist at the Children’s Hospital of the King’s Daughters, and colleagues assessed the safety and efficacy of intrathecal onasemnogene abeparvovec (OA; Zolgensma, Novartis), an adeno-associated vector-based gene therapy for SMA, in the STEER clinical trial, a phase 3, multicenter, randomized, sham-controlled, double-blind study.
The study included 126 treatment-naïve, nonambulatory patients with SMA aged 2 to 18 years who were randomly assigned on a 3:2 basis to receive either OA (n = 75; mean age, 5.89 years; 54.7% girls) or sham (n = 51; mean age 5.87 years; 54.9% boys).
The primary outcome was comparative efficacy measured as change from baseline in Hammersmith Functional Motor Scale – Expanded (HFMSE) total score over 52 weeks. Secondary outcomes included improvement of at least three points in HFMSE score and change from baseline in the Revised Upper Limb Module (RULM) at 52 weeks for the total study population, as well as total change from baseline in HFSME and RULM and improvement of at least three points in HFMSE at week 52 for those aged 2 to younger than 5 years.
Proud and colleagues also conducted safety assessments to evaluate adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI), along with liver function evaluations.
According to the results, patients treated with OA registered an improvement of 2.39 points in the HFMSE at 52 weeks, compared with 0.51 points for patients given sham treatment.
In the overall study population, data showed the treatment cohort logged an improvement of 2.44 points in the RULM vs. 0.92 points for the sham cohort, while 29 of 74 patients given OA (39.2%) posted a 3-point increase in the HFMSE against 13 of 50 (26%) given sham treatment.
Patients aged 2 to 4 years who received OA had an improvement of three points vs. 1.56 for the sham cohort in HFSME, with an improvement of 3.27 vs. 1.82 in RULM. Nine of 33 (27.3%) patients in this cohort recorded a three-point HFSME improvement in the OA group vs. two of 21 (9.5%) for sham.
Proud and colleague reported that the overall incidence of adverse events, serious adverse events and adverse events of special interest were similar between both groups. The most common reported adverse events were upper respiratory tract infection and pyrexia, while the most frequent serious adverse events were pneumonia and vomiting for the treatment group and pneumonia and lower respiratory tract infection for sham.
“Results from both trials support the potential of this therapy to provide patients the opportunity to avoid repeated treatment administration while maintaining or improving motor function among patients,” Grant said.
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Proud C, et al. Intrathecal onasemnogene abeparvovec for patients with spinal muscular atrophy: Phase 3 randomized, sham-controlled, double-blind STEER study. Presented at: Muscular Dystrophy Association Clinical & Scientific Conference; March 16-19, 2025; Dallas.
