Apitegromab, a Novel High-Affinity Anti-proMyostatin Monoclonal Antibody for Treating Spinal Muscular Atrophy: Results of a Phase 2 Interim Analysis


Clinical Trials

Poster Number: 51


Amy Place PhD, MBA, MS, RD, CLT


1. Scholar Rock

Background: Apitegromab (SRK-015) is a fully human, high-affinity anti-proMyostatin monoclonal antibody that binds to human proMyostatin and latent myostatin and inhibits the tolloid-mediated proteolysis step for myostatin activation. As proMyostatin is the predominant form of myostatin in skeletal muscle, apitegromab inhibits myostatin activation directly in target tissues.
Objectives: The primary objectives of this 52-week phase 2 trial (TOPAZ) were to assess safety and tolerability of apitegromab, administered by IV infusion every 4 weeks, in subjects with Type 2 and Type 3 spinal muscular atrophy (SMA) and measure changes in motor function. Secondary objectives were to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) effects of apitegromab, therapeutic effects of low- (2 mg/kg) and high-dose (20 mg/kg) apitegromab, immunogenicity and other exploratory motor function measures. Subjects received apitegromab as monotherapy or with an approved SMN upregulator (nusinersen). The primary endpoint was mean change in baseline Hammersmith Scale scores. Results: Subjects in Cohort 1 (ambulatory Type 3, n=23), who received apitegromab (20 mg/kg) as monotherapy or as an adjunctive treatment to nusinersen, had a pooled mean change in baseline Revised Hammersmith Scale (RHS) scores of 0.5 (-1.1, 2.2). Cohorts 2 (n=14) and 3 (n=18) included Type 2 and non-ambulatory Type 3 subjects, who received apitegromab (Cohort 2, 20 mg/kg; Cohort 3, 2 mg/kg and 20 mg/kg) as an adjunctive treatment to nusinersen. Subjects in Cohort 2 achieved a mean change in baseline Hammersmith Functional Motor Scale Expanded (HFMSE) scores of 1.4 (0.1, 2.7). In the low-dose Cohort 3 group, the mean change in baseline HFMSE scores was 2.4 (-0.9, 5.8). In the high dose Cohort 3 group, the mean change in baseline HFMSE scores was 5.6 (2.5, 8.7).
Conclusion: Safety and tolerability, PK/PD and responder analysis data (secondary efficacy) from the TOPAZ interim analysis will be presented.