Intrathecal Onasemnogene Abeparvovec for Patients with Spinal Muscular Atrophy: Phase 3, Randomized, Sham-Controlled, Double-Blind STEER Study

Topic:

Clinical Trials

Poster Number: LB450

Author(s):

Crystal Proud, Children’s Hospital of the King’s Daughters, Norfolk, VA, USA, Jo M. Wilmshurst, Red Cross War Memorial Children’s Hospital, University of Cape Town, Oranee Sanmaneechai, Siriraj Hospital, Mahidol University, Sheffali Gulati, AIIMS, Hui Xiong, Children’s Medical Center, Peking University First Hospital, Hugo Ceja Moreno, Hospital Civil de Guadalajara Fray Antonio Alcalde, Stacey Kiat Hong Tay, Yong Loo Lin School of Medicine, National University of Singapore, Meow-Keong Thong, University of Malaya, Alfred Peter Born, Rigshospitalet, Copenhagen University Hospital, Adriana Banzzatto Ortega, Hospital Pequeno Príncipe, Yuh-Jyh Jong, MD, DMSci, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Mohammad Al-Muhaizea, King Faisal Specialist Hospital & Research Centre, Richard S. Finkel, MD, Center for Experimental Neurotherapeutics, St. Jude Children’s Research Hospital, Anna W. Lee, Novartis Pharmaceuticals Corporation, Jeannie Visootsak, MD, Novartis Pharmaceuticals Corporation, Sitra Tauscher-Wisniewski, MD, Novartis Gene Therapies, Inc., Iulian Alecu, MD, Novartis Pharmaceuticals, Shihua Wen, Novartis Pharmaceuticals Corporation, Dũng Chí Vũ, Vietnam National Children’s Hospital, STEER Study Group, N/A

Background: While the availability of disease-modifying therapeutic options has changed the clinical course of SMA, significant unmet need remains for a broader patient population. Onasemnogene abeparvovec (OA) for intrathecal administration is an adeno-associated vector-based gene therapy under development for the treatment of spinal muscular atrophy (SMA) in older patients.
Objective: STEER (NCT05089656) is a phase 3, multicenter, multinational, randomized, sham-controlled, double-blind trial to investigate the efficacy and safety of intrathecal OA over 52 weeks in treatment-naïve, sitting and never ambulatory patients with SMA aged 2 to <18 years. The primary objective is to compare the efficacy (OA vs. sham) by change from baseline in Hammersmith Functional Motor Scale – Expanded (HFMSE) total score over 52 weeks. Secondary objectives include additional efficacy and safety assessments. Results: 136 patients were randomized (3:2 ratio), with 126 patients receiving either OA (n=75) or a sham procedure (n=51). Mean (range) age at dosing was 5.88 (2.1–16.6) years. The study met its primary endpoint, demonstrating a statistically significant increase from baseline in HFMSE total score in the OA group compared with the sham control. The overall incidence of adverse events (AEs), serious AEs (SAEs), and AEs of special interest were similar between both groups. The most common AEs for both groups were upper respiratory tract infection and pyrexia. The most frequent SAEs were pneumonia and vomiting for the OA group and pneumonia and lower respiratory tract infection for the sham group. Instances of transaminase increases were infrequent; most were low-grade and transient. There were no cases of Hy’s law. Conclusions: A one-time intrathecal OA infusion resulted in statistically significant improvement in motor function compared with sham control and demonstrated a favorable safety profile for older patients with SMA.