
The muscle-targeting monoclonal antibody apitegromab was safe and significantly improved motor function in patients aged 2 to 21 with type 2 and type 3 spinal muscular atrophy (SMA), according to results of the phase-3 SAPPHIRE trial presented at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference.
According to the abstract by Tom Crawford, MD, of John Hopkins Medicine, and colleagues, patients with SMA experience progressive loss of motor function despite treatment with survival motor neuron (SMN) protein targeting therapies.
SAPPHIRE was designed to evaluate whether apitegromab could improve baseline Hammersmith Functional Motor Scale – Expanded (HFMSE) at 12 months. Dr. Crawford and colleagues enrolled 188 participants aged 2-21 years with nonambulatory SMA receiving SMN therapy with nusinersen/risdiplam.
Patients aged 2 to 12 were randomly assigned 1:1:1 to apitegromab 10 mg/kg, apitegromab 20 mg/kg, or placebo every four weeks. Patients aged 13-21 were randomly assigned 2:1 to apitegromab 20 mg/kg or placebo.
Apitegromab significantly improved HFMSE from baseline in patients aged 2 to 12 (mean difference was 1.8 points for combined doses vs. placebo; P=.0192); the mean difference in HFMSE change from baseline was 1.8 points with apitegromab versus placebo for participants aged 13-21 as well.
Pharmacodynamic analyses suggested that both doses resulted in target saturation. Observed adverse events were consistent with the underlying disease and with SMN therapy. There was no study discontinuation because of adverse events.
In March, the Food and Drug Administration granted apitegromab Priority Review.
Reference
Crawford T, Darras BT, Servais L, et al. Efficacy and safety of apitegromab in individuals with type 2 and type 3 spinal muscular atrophy evaluated in the phase 3 SAPPHIRE trial. O284. Presented at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference.