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

Topic:

Clinical Trials

Poster Number: P276

Author(s):

John F Brandsema, MD, Children's Hospital of Philadelphia, Philadelphia, PA, USA, Crystal Proud, MD, Children’s Hospital of the King’s Daughters, Richard S Finkel, MD, St. Jude Children’s Research Hospital, Julie A Parsons, MD, Children’s Hospital Colorado, Aurora, CO, USA, Riccardo Masson, MD, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy, Nancy L. Kuntz, MD, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Med, Richard Foster, MSc, Biogen, Maidenhead, Berkshire, UK, Wenjing Li, PhD, Biogen, Cambridge, MA, USA, Ross Littauer, PhD, Biogen, Cambridge, MA, USA, Jihee Sohn, PhD, Biogen, Cambridge, MA, USA, Bora Youn, PhD, Biogen, Cambridge, MA, USA, Stephanie Fradette, PharmD, Biogen, Angela D Paradis, ScD, Biogen, Cambridge, MA, USA

Submitted on behalf of the RESPOND Study Group

RESPOND (NCT04488133) is evaluating nusinersen in children with SMA who have previously received OA and have suboptimal clinical status in ≥1 domains at baseline: motor function, swallow/feeding ability, respiratory function, other. Of 37 who reached Day (D) 302 (data-cut: 18Oct2023), 21 were age ≤9 mo at first nusinersen dose with 2 SMN2 copies (group 1 [G1]), 13 were age >9 mo with 2 copies (group 2 [G2]), and 3 were age >9 mo with 3 copies (group 3 [G3]). Median age at baseline in each group was 8.2 mo, 15.9 mo, and 34.2 mo, respectively. All were symptomatic at OA dosing. Mean change from baseline to D302 in total HINE-2 was 8.7 points in G1 and 6.9 points in G2 (not calculated in G3 due to small sample size); mean D302 score was 11.6 and 15.2 points in each group. Of 27 children unable to sit at baseline, 14 (52%) achieved sitting by D302. Baseline plasma neurofilament light chain (NfL) levels were elevated, suggestive of active neurodegeneration at study entry (G1 mean, 132.0 pg/mL; G2 mean, 121.0 pg/mL). Mean levels decreased from baseline to D302 by 77% and 82% in G1 and G2, with consistent pattern of decline by age and time from OA dose. Mean CMAP ulnar-abductor digiti minimi and peroneal-tibialis anterior amplitude increased from baseline to D302. Safety set included 46 children on study for a median of ~562 days; AEs occurred in 37 (80%). Three (7%) children had a nusinersen-related mild AE (proteinuria). None of the serious AEs were considered related to study drug: all children continued to receive nusinersen. In conclusion, continued improvements in clinical and biomarker outcomes support the benefit of nusinersen treatment in children with suboptimal clinical response to OA. Safety was consistent with nusinersen’s safety profile.