LB: Intrathecal Onasemnogene Abeparvovec (OAV101) for Patients with Spinal Muscular Atrophy (SMA): Extended 64-Week Outcomes from the Phase 3 STEER Study

Topic:

Clinical Trials

Poster Number: 481 LBT

Author(s):

Crystal Proud, PhD, Children’s Hospital of The King’s Daughters, Richard S. Finkel, MD, Center for Experimental Neurotherapeutics, St. Jude Children’s Research Hospital, Jo M. Wilmshurst, MBBS, MD, MRCP (London), FCPae, Red Cross War Memorial Children’s Hospital, University of Cape Town, Oranee Sanmaneechai, MD, Siriraj Hospital, Mahidol University, Sheffali Gulati, FRCPCH (UK), FAMS, FIAP, FIMSA, AIIMS, Hui Xiong, MD, PhD, Children’s Medical Center, Peking University First Hospital, Stacey Kiat Hong Tay, MBBS (Hons), S'pore; FAMS, S'p, Yong Loo Lin School of Medicine, National University of Singapore, Ratna Dua Puri, MD, DM, Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, Neelu Desai, MD, DNB, P.D. Hinduja National Hospital and Medical Research Centre, Li Liu, Guangzhou Women and Children’s Medical Center, Xufeng Luo, West China Second University Hospital, Ahmad Rithauddin Mohamed, Hospital Tunku Azizah Paediatric Department, Daniel Alvarez-Amado, MD, Hospital Infantil de México Federico Gómez, Anna W. Lee, PhD, Novartis Pharmaceuticals Corporation, Gemma Williams, MBBS, PhD, Novartis Pharmaceuticals, Roberto Bernardo Escudero, MD, Novartis Pharmaceuticals Corporation, Rutvick Parlikar, BSc, MA, Novartis Healthcare Pvt. Ltd., Nicolas Ballarini, MS, PhD, Novartis, Dũng Chí Vũ, MD, PhD, Vietnam National Children’s Hospital

Background: STEER (NCT05089656) was a phase 3, multicenter, randomized, sham‑controlled, double‑blind study evaluating the efficacy and safety of single‑dose intrathecal (IT) OAV101 in treatment‑naive, sitting and never‑ambulatory patients with SMA aged 2 to <18 years.
Objective: The primary objective—comparing OAV101 IT vs sham in change from baseline in HFMSE through Week 52—was met, with OAV101 IT demonstrating a statistically significant, clinically meaningful increase in HFMSE compared with sham. Eligible patients completing the 52‑week comparative phase entered a second part with 3 additional months of follow‑up.
Results: Patients were randomized to OAV101 IT or sham and followed through Week 52. From Week 52 + 1 day to Week 64, sham‑treated patients switched to OAV101 IT, and those initially treated with OAV101 IT received sham. This analysis reports efficacy outcomes for patients who received OAV101 IT in the first part, with HFMSE and RULM changes from baseline evaluated through Week 64. Cumulative safety was assessed for all patients who received OAV101 IT.
A total of 126 patients received study treatment (n=75 OAV101 IT; n=51 sham) during the first part of the study. Of the 75 OAV101 IT-treated patients, 67 continued into the second part; 46 of 51 sham patients entered the second part and received OAV101 IT. During the combined follow-up period of 15-months post‑treatment, mean HFMSE scores continued to increase, demonstrating sustained and progressive motor function gains without other SMN‑targeted therapy. Least‑squares mean (LSM) HFMSE changes from baseline were 2.41 (95% CI: 1.54–3.27) at Week 52 and 2.75 (95% CI: 1.61–3.88) at Week 64. LSM change from baseline in RULM increased from 2.47 (95% CI: 1.72–3.21) at Week 52 to 2.93 (95% CI: 2.04–3.81) at Week 64. The most common AEs among all OAV101 IT–treated patients (n=121) were upper respiratory tract infection (28.1%), pyrexia (19.8%), and vomiting (18.2%). AEs of special interest included hepatotoxicity (8.3%), transient thrombocytopenia (7.4%), and signs/symptoms that may be suggestive of dorsal root ganglia toxicity (2.5%). Transaminase elevations were generally mild and transient, with no Hy’s law cases.
Conclusions: Patients receiving OAV101 IT in STEER demonstrated continued motor improvement through Week 64. The cumulative safety profile of OAV101 IT through Week 64 was consistent with the comparative phase of the study, with no new safety signals identified.