Apitegromab Improves Motor Function in Children With SMA
Treatment with the fully human monoclonal antibody apitegromab was associated with statistically significant improvements in motor function scores compared with placebo in patients with type 2 or type 3 spinal muscular atrophy (SMA), according to results from the phase 3 SAPPHIRE trial published in The Lancet Neurology.
The double-blind trial included 188 patients with type 2 or type 3 SMA at 48 hospitals in the United States and Europe. Patients had received at least 10 months of nusinersen or at least 6 months of risdiplam therapy prior to the trial.
Apitegromab is designed to selectively inhibit myostatin activation, a biological process known to limit muscle growth. Researchers randomized 156 patients aged 2 to 12 years to apitegromab 20 mg/kg, apitegromab 10 mg/kg, or placebo, and 32 patients aged 13 to 21 years to apitegromab 20 mg/kg or placebo, every 4 weeks.
Overall, 128 patients received apitegromab, and 60 patients received placebo. The trial’s primary endpoint was change from baseline in Hammersmith Functional Motor Scale-Expanded (HFMSE) scores at 12 months.
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In patients aged 2 to 12 treated with apitegromab, HFMSE scores significantly improved compared with patients treated with placebo, the study found.
“All of these individuals could sit or walk, but they did not have normal mobility,” said researcher Nancy Kuntz, MD, medical director of the Mazza Foundation Neuromuscular Program at Ann & Robert H. Lurie Children’s Hospital of Chicago and a pediatrics professor at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “While improvements seen on the drug were not something that would be the difference between being bedridden and walking, the changes led to functional independence.”
According to the study, the least squares mean difference in HFMSE change from baseline was 1.8 points for participants aged 2 to 12 years receiving apitegromab compared with placebo. The least squares mean difference was 1.4 for apitegromab 20 mg/kg versus placebo.
Adverse events with apitegromab and placebo were comparable and consistent with SMA and background SMA therapy. No patients discontinued the trial because of adverse events.
“Participants in the apitegromab treatment groups (combined 20 mg/kg and 10 mg/kg dose) achieved statistically significant improvements in motor function compared with placebo; however, the least squares mean difference was not significant between apitegromab 20 mg/kg and placebo,” wrote corresponding author Thomas O. Crawford, MD, of Johns Hopkins Medicine, Baltimore, Maryland, and study coauthors.
“Overall, SAPPHIRE results build on findings from the phase 2 TOPAZ trial, showing improved motor function with a generally well tolerated safety profile, supporting the use of muscle-targeting therapy for spinal muscular atrophy.”
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