Interim results from the RESPOND study of nusinersen in children with spinal muscular atrophy (SMA) previously treated with onasemnogene abeparvovec


Clinical Trials

Poster Number: S111


John F. Brandsema, MD, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Riccardo Masson, MD, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy, Crystal Proud, MD, Children’s Hospital of the King’s Daughters, Julie Parsons, MD, Children's Hospital Colorado, Nancy Kuntz, MD, Ann & Robert H. Lurie Children's Hospital, Richard Finkel, MD, St. Jude Children’s Research Hospital, Kathryn J Swoboda, MD, Massachusetts General Hospital, Boston, MA, USA, Richard Foster, MSc, Biogen, Maidenhead, Berkshire, UK, Wenjing Li, Biogen, Cambridge, MA, USA, Samata Singhi, Biogen, Cambridge, MA, USA, Bora Youn, PhD, Biogen, Cambridge, MA, USA, Angela D Paradis, ScD, Biogen, Cambridge, MA, USA, Shweta Rane, Biogen, Cambridge, MA, USA

Background: RESPOND (NCT04488133) is a single-arm study evaluating nusinersen (NUS) in participants (pts) with SMA who previously received onasemnogene abeparvovec (OA) and have suboptimal clinical status per the investigator in ≥1 of 4 domains at baseline (BL): motor function, swallowing/feeding ability, respiratory function, and other.
Objectives: To report baseline (BL) characteristics and interim clinical outcomes and safety findings.
Results: At the data cut (15 Nov 2022), 38 pts were enrolled and dosed for a median of ~230 days. Twenty-nine pts who reached Day 183 were assessed for clinical outcomes: 14 were ≤9 mo of age at first NUS dose and had 2 SMN2 copies (group 1 [G1]; median [range] age: 7.7 [3.4–9.8] mo), 12 were >9 mo of age with 2 SMN2 copies (group 2 (G2); 16.3 [11.0-33.3]), and 3 were >9 mo of age with 3 SMN2 copies (group 3 (G3); 30.8 [29.2–35.7]). All were symptomatic at OA dosing (median [range] age at OA: 1.7 [0.7–5.1] mo in G1; 2.7 (0.8–6.9) in G2; 17.5 [13.6–24.3] in G3). At BL, most had low ulnar CMAP amplitude (≤1 mV), and 93% of pts in G1, 92% in G2, and 33% in G3 had investigator-reported suboptimal clinical status in ≥2 domains. At Day 183, most pts with suboptimal motor function at BL reported improvement (92% in G1, 91% in G2, 100% in G3). Investigators most often reported no change in suboptimal swallowing/feeding ability or respiratory function, but some reported improvement. Mean (SD) change from BL to Day 183 in total HINE-2 scores was 5.4 (2.6) in G1 and 5.2 (2.7) in G2 (not calculated in G3 due to small sample size). Mean (SD) scores at Day 183 reached 8.6 (3.5) and 13.5 (5.8) in each group, respectively. On average, pts who were unable to sit without support improved on CHOP INTEND. Mean (SD) changes in CHOP INTEND were 6.7 (6.8) and 3.6 (3.9) in nonsitters in G1 and G2. Adverse events (AEs) occurred in 31/38 (82%) pts, most commonly infections/infestations (63%) and respiratory, thoracic, and mediastinal disorders (26%). Two (5%) pts had an AE determined by the investigator to be related to NUS (mild proteinuria), which resolved. Thirteen (34%) had serious AEs; none related to NUS. Additional data will be presented.
Conclusions: Most pts showed suboptimal clinical status in multiple domains at BL. At Day 183, the majority of pts receiving NUS showed improvements in motor function. Reported interim safety outcomes are consistent with the established safety profile of NUS.
Study Support: Biogen