170P Apitegromab in spinal muscular atrophy: baseline characteristics of participants enrolled in the phase 3 SAPPHIRE study

• Published in: Neuromuscular disorders : NMD 2024-10, Vol.43, p.104441, Article 104441.605
• Main Authors: Crawford, T., Servais, L., Krueger, J., Kölbel, H., Garcia, M. Gomez, Cances, C., Kuntz, N., Finkel, R., Yao, B., Zhao, G., Marantz, J., Darras, B., Mercuri, E.
• Format: Article
• Language: English
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2024.07.614

Spinal muscular atrophy (SMA), a progressive genetic neuromuscular disorder resulting in neurodegeneration, skeletal muscle atrophy, and weakness, typically manifests in infancy and is associated with high morbidity. Current SMA therapies target motor neurons; however, motor function deficits remain due to muscle atrophy. Apitegromab, a fully human monoclonal antibody that inhibits activation of latent myostatin and enables muscle growth, is an investigational SMA treatment. The phase 3, randomized, double-blind, placebo-controlled SAPPHIRE (NCT05156320) study is evaluating efficacy and safety of apitegromab in nonambulatory patients with type 2 or 3 SMA aged ≥2y receiving SMN therapy (≥10mo nusinersen or ≥6mo risdiplam) with Hammersmith Functional Motor Scale Expanded (HFMSE) scores of ≥10 and ≤45 at screening. A main efficacy population (MEP; 2y–12y) and exploratory subpopulation (EXP; 13y–21y) will be assessed for 12mo. The MEP was randomized 1:1:1 to receive 10 or 20 mg/kg apitegromab or placebo every 4 weeks (Q4W) and the EXP 2:1 to receive 20 mg/kg apitegromab or placebo Q4W. At enrollment, the MEP (mean age, 7.8y, n=156) and EXP (15.8y; n=32) was 47.4% and 62.5% female, respectively. Mean±SD age at SMN therapy initiation was 3.2y±1.6y in the MEP, with 77.6% receiving nusinersen vs risdiplam, and 11.0y±3.8y in the EXP (nusinersen, 56.3%). Most participants had 3 SMN2 copies (MEP, 83.3%; EXP, 62.5%). Mean±SD baseline total HFMSE and Revised Upper Limb Module (RULM) scores were 26.2±10.1 and 26.2±6.1 in the MEP and 21.3±10.3 and 26.3±5.7 in EXP, respectively; World Health Organization (WHO) motor milestones met were 1.6±0.9 for MEP and 1.3±0.8 for EXP. Despite SMN-targeted therapy, low baseline HFMSE and RULM scores and WHO milestones met indicate prevalent motor function deficits. The study will assess if apitegromab addresses this unmet need by directly targeting muscle atrophy to enhance motor function.