A plain language summary of the SAPPHIRE clinical trial of apitegromab in children and young adults with spinal muscular atrophy

Plain language summary

What was the trial about?Spinal muscular atrophy (SMA) is a rare and serious progressive, worsening genetic disease. Children and adults living with SMA have low levels of a protein called the survival motor neuron (SMN) protein. Without enough of this protein, the nerve cells that control muscles (motor neurons) begin to die. As a result, the muscles become smaller (a condition called muscle atrophy) and weaker. Over time, this leads to a loss of normal movement (called motor function) and muscle control.Treatments that increase SMN protein levels (SMN-targeted treatments) improve motor neuron survival and thus overall motor function. However, many individuals living with SMA who are taking these treatments still experience reduced motor function compared with people without SMA.A new potential treatment called apitegromab directly targets myostatin in muscles to improve motor function. This summary describes the SAPPHIRE clinical trial. In this study, patients with SMA who were already receiving treatments that target the SMN protein (SMN-targeted treatments), also received apitegromab.What was the objective?The aim of the SAPPHIRE trial was to see how well apitegromab worked and what side effects it might cause over one year. The study compared apitegromab to a placebo treatment in patients with SMA who were already receiving SMN-targeted treatments.What were the results?After 1 year of continued treatment, motor function improved in patients treated with apitegromab compared with those who received placebo. Improvements with apitegromab were seen across different age groups and different dose levels. Patients tolerated apitegromab well, meaning that side effects were similar between patients receiving apitegromab or placebo and side effects caused by apitegromab were minimal. Most of the side effects were either common among people living with SMA or likely caused by the SMN-targeted treatments the patients were already receiving.What do the results mean?These results suggest that directly targeting muscles with apitegromab has the potential to improve motor function for people living with SMA who are already receiving SMN-targeted treatments.

Keywords: Apitegromab; Motor; Motor neuron; Muscle; Myostatin; Neuromuscular; Plain language summary; Spinal Muscular Atrophy.