Intrathecal onasemnogene abeparvovec in treatment-naive patients with spinal muscular atrophy: a phase 3, randomized controlled trial
1
Issued Date
2025-01-01
Resource Type
ISSN
10788956
eISSN
1546170X
Scopus ID
2-s2.0-105025127609
Pubmed ID
41360993
Journal Title
Nature Medicine
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Medicine (2025)
Suggested Citation
Proud C.M., Vũ D.C., Wilmshurst J.M., Sanmaneechai O., Gulati S., Xiong H., Moreno H.C., Tay S.K.H., Thong M.K., Born A.P., Banzzatto Ortega A., Jong Y.J., Al-Muhaizea M.A., Lee A.W., Visootsak J., Tauscher-Wisniewski S., Alecu I., Parlikar R., Finkel R.S., Jong Y.J., Ortega A.B., Thong M.K., Vũ D.C. Intrathecal onasemnogene abeparvovec in treatment-naive patients with spinal muscular atrophy: a phase 3, randomized controlled trial. Nature Medicine (2025). doi:10.1038/s41591-025-04103-w Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113672
Title
Intrathecal onasemnogene abeparvovec in treatment-naive patients with spinal muscular atrophy: a phase 3, randomized controlled trial
Author's Affiliation
Universiti Malaya
Rigshospitalet
All India Institute of Medical Sciences, New Delhi
NUS Yong Loo Lin School of Medicine
Kaohsiung Medical University
Novartis International AG
St. Jude Children's Research Hospital
National Yang Ming Chiao Tung University
Peking University First Hospital
Siriraj Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
King Faisal Specialist Hospital & Research Centre
Universiti Tunku Abdul Rahman
Beijing Children's Hospital, Capital Medical University
Red Cross War Memorial Children's Hospital
Hospital Civil de Guadalajara
Children's Hospital of The King's Daughters Health System
Hanoi School of Public Health
Novartis India Limited
Vietnam National Children's Hospital
Hospital Infantil Pequeño Principe
Rigshospitalet
All India Institute of Medical Sciences, New Delhi
NUS Yong Loo Lin School of Medicine
Kaohsiung Medical University
Novartis International AG
St. Jude Children's Research Hospital
National Yang Ming Chiao Tung University
Peking University First Hospital
Siriraj Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
King Faisal Specialist Hospital & Research Centre
Universiti Tunku Abdul Rahman
Beijing Children's Hospital, Capital Medical University
Red Cross War Memorial Children's Hospital
Hospital Civil de Guadalajara
Children's Hospital of The King's Daughters Health System
Hanoi School of Public Health
Novartis India Limited
Vietnam National Children's Hospital
Hospital Infantil Pequeño Principe
Corresponding Author(s)
Other Contributor(s)
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.