Intrathecal onasemnogene abeparvovec in treatment-naive patients with spinal muscular atrophy: a phase 3, randomized controlled trial

STEER ( NCT05089656 ) was a 52-week, phase 3, multicenter, randomized, sham-controlled, double-blind trial evaluating intrathecal onasemnogene abeparvovec (OAV101 IT), a one-time gene transfer therapy, in patients with spinal muscular atrophy (SMA). Participants ranged in age from 2 years to <18 years, were treatment-naive and were able to sit but never walked independently. Primary efficacy endpoint was change from baseline in Hammersmith Functional Motor Scale-Expanded (HFMSE) score. In total, 126 patients received OAV101 IT (n = 75) or a sham procedure (n = 51). The primary endpoint was met: patients treated with OAV101 IT demonstrated a significant increase in HFMSE score compared with sham (least squares mean difference, 1.88 (95% confidence interval: 0.51-3.25); P = 0.0074). Overall incidence of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) was similar between groups. Transaminase increases were infrequent; most were low grade and transient. Two participants in the OAV101 IT arm and one participant in the sham arm developed sensory symptoms. One-time OAV101 IT demonstrated a statistically significant improvement in motor function compared with sham control. The overall safety findings were acceptable, with similar incidences of AEs, SAEs and AESI in the OAV101 IT and sham groups. Trial registration: ClinicalTrials.gov identifier: NCT05089656 .

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Publication Details

Journal
Nature Medicine
Published
2025-12-08
DOI
https://doi.org/10.1038/s41591-025-04103-w
Citations
4
Primary Topic
Neurogenetic and Muscular Disorders Research
Type
article
Field-Weighted Citation Impact
6.50

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article

Intrathecal onasemnogene abeparvovec in treatment-naive patients with spinal muscular atrophy: a phase 3, randomized controlled trial

Mohammad A. Al–Muhaizea, Iulian Alecu, Jo M. Wilmshurst, Oranee Sanmaneechai et al.
4 citations
Nature Medicine
Neurogenetic and Muscular Disorders Research
6.50
article

Intrathecal onasemnogene abeparvovec in treatment-naive patients with spinal muscular atrophy: a phase 3, randomized controlled trial

Mohammad A. Al–Muhaizea, Iulian Alecu, Jo M. Wilmshurst, Oranee Sanmaneechai, S K Tay, Jeannie Visootsak, Yuh‐Jyh Jong, Anna W. Lee, Sitra Tauscher‐Wisniewski, Heitor Moreno, Dzung H. Vu, Crystal M. Proud, Sheffali Gulati, Rutvick Parlikar, Richard S. Finkel, Meow‐Keong Thong, Adriana Banzzatto Ortega, Alfred Peter Born, Hui Xiong
article en
4 citations

Abstract

STEER ( NCT05089656 ) was a 52-week, phase 3, multicenter, randomized, sham-controlled, double-blind trial evaluating intrathecal onasemnogene abeparvovec (OAV101 IT), a one-time gene transfer therapy, in patients with spinal muscular atrophy (SMA). Participants ranged in age from 2 years to <18 years, were treatment-naive and were able to sit but never walked independently. Primary efficacy endpoint was change from baseline in Hammersmith Functional Motor Scale-Expanded (HFMSE) score. In total, 126 patients received OAV101 IT (n = 75) or a sham procedure (n = 51). The primary endpoint was met: patients treated with OAV101 IT demonstrated a significant increase in HFMSE score compared with sham (least squares mean difference, 1.88 (95% confidence interval: 0.51-3.25); P = 0.0074). Overall incidence of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) was similar between groups. Transaminase increases were infrequent; most were low grade and transient. Two participants in the OAV101 IT arm and one participant in the sham arm developed sensory symptoms. One-time OAV101 IT demonstrated a statistically significant improvement in motor function compared with sham control. The overall safety findings were acceptable, with similar incidences of AEs, SAEs and AESI in the OAV101 IT and sham groups. Trial registration: ClinicalTrials.gov identifier: NCT05089656 .

Nature MedicineVol. 32(2)
Novartis (Switzerland) (CH), St. Jude Children's Research Hospital (US), Siriraj Hospital (TH), National Yang Ming Chiao Tung University (TW), Kaohsiung Medical University (TW), University of Cape Town (ZA), National University of Singapore (SG), Capital Medical University (CN), Peking University (CN), Mahidol University (TH), King Faisal Specialist Hospital & Research Centre (SA), Copenhagen University Hospital (DK), Kaohsiung Medical University Chung-Ho Memorial Hospital (TW), Rigshospitalet (DK), University of Malaya (MY), Novartis (India) (IN), Hospital Erasto Gaertner (BR), Novartis (United States) (US), Hospital Civil de Guadalajara (MX), Peking University First Hospital (CN), Vietnam National Children's Hospital (VN), Children's Hospital of The King's Daughters (US), Beijing Children’s Hospital (CN), Child Development Center (QA), Red Cross War Memorial Children's Hospital (ZA), Hanoi School Of Public Health (VN), All India Institute of Medical Sciences (IN), Hanoi University (VN), Universiti Tunku Abdul Rahman (MY)
Guangzhou Medical University, Peking University First Hospital, Ain Shams University, King Faisal Specialist Hospital and Research Centre, Capital Medical University, Chongqing Medical University, Universiti Malaya, Kaohsiung Medical University, Zhejiang University, Sichuan University, Region Hovedstaden, Universidade de São Paulo, Faculdade de Medicina da Universidade de São Paulo, Universidade Estadual de Campinas, University of Cape Town, Peking University, Hospital Infantil de México Federico Gómez, National Healthcare Group, Kaohsiung Medical University Chung-Ho Memorial Hospital, Novartis Pharma, Beijing Children's Hospital, Capital Medical University, Faculty of Medicine Siriraj Hospital, Mahidol University
Openalex Percentile: Top 3%
Neurogenetic and Muscular Disorders Research
6.50
DOIOpen Access PDFOpenAlex
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