Efficacy and safety of apitegromab in individuals with type 2 and type 3 spinal muscular atrophy evaluated in the phase 3 SAPPHIRE trial

Topic:

Clinical Trials

Poster Number: O284

Author(s):

Tom Crawford, MD, John Hopkins Medicine, Basil T Darras, MD, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA, Laurent Servais, MD, PhD, MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre, Oxford, UK, Jena Krueger, MD, Helen Devos Children’s Hospital, Heike Kölbel, MD, University Hospital Essen, Essen, DE, Andreea Seferian, MD, Institut I-Motion, Hôpital Trousseau, 26 avenue du Dr Arnold Netter, Paris, France;, Claude Cances, MD, Toulouse University Hospital, Toulouse, FR, Nancy L. Kuntz, MD, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Med, Richard S Finkel, MD, St. Jude Children’s Research Hospital, Bert Yao, MD, PhD, Scholar Rock, Inc., Cambridge, MA, USA, Jose Rossello, MD, PhD, MHCM, Scholar Rock, Inc., Cambridge, MA, USA, Guolin Zhao, MA, PhD, Scholar Rock, Inc., Cambridge, MA, USA, Guochen Song, MS, Scholar Rock, Inc., Cambridge, MA, USA, Jing Marantz, MD, PhD, Scholar Rock, Eugenio Mercuri, MD, PhD, Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemel

Patients with SMA may continue to experience progressive loss of motor function despite SMN therapies. SAPPHIRE (NCT05156320) is a double-blind, global, placebo-controlled phase 3 trial assessing apitegromab, a muscle-targeting monoclonal antibody, in participants with nonambulatory SMA aged 2–21 years receiving SMN therapy (nusinersen/risdiplam). Participants 2–12 years were randomized 1:1:1 for apitegromab 10mg/kg or 20mg/kg or placebo Q4W; those 13–21 years were randomized 2:1 for apitegromab 20mg/kg or placebo. Primary efficacy endpoint was change from baseline (CFB) in HFMSE at 12 months. Secondary endpoints included RULM, proportion achieving HFMSE ≥3-point change, WHO motor development milestones, PK/PD, and safety.

Overall, 188 participants enrolled: 156 in the 2–12 and 32 in the 13–21 populations. The primary endpoint was achieved, with statistically significant and clinically meaningful motor function improvement: mean difference in HFMSE CFB was 1.8 points (P=0.0192) for the 2–12 main efficacy population receiving apitegromab (combined doses, n=106) vs placebo (n=50). Mean difference in HFMSE CFB was 1.4 (P=0.1149) for apitegromab 20mg/kg (n=53) vs placebo and 2.2 (nominal P=0.0121) for apitegromab 10mg/kg vs placebo. PD effect was similar for apitegromab 10mg/kg and 20mg/kg, indicated by superimposable total latent myostatin levels, suggesting target saturation at both doses. In addition to consistency across doses, apitegromab demonstrated consistency across age groups; mean difference vs placebo in HFMSE CFB was 1.8 for both 2–12 and 13–21 populations as well as the entire study population (2–21). HFMSE improved for participants receiving apitegromab but decreased for those on placebo; the separation was evident by the 8-week assessment and widened by 12 months. AEs were consistent with underlying disease and SMN therapy. No participants discontinued due to AEs. Additional data will be presented.

Apitegromab provided significant improvement in motor function across ages and doses and was generally safe and well-tolerated.