SMA: motor function improved with an anti-myostatin treatment
Treatment with apitegromab, which acts directly on muscles, appears to improve motor function in patients already treated with Spinraza or Evrysdi, according to a trial involving nearly 200 patients with type II or III spinal muscular atrophy.
In 5q spinal muscular atrophy linked to SMN1 (SMA), the arrival of treatments such as Spinraza, Zolgensma and Evrysdi, designed to compensate for the loss of SMN protein, has considerably improved patients’ lives, although motor deficits may still persist. Apitegromab is a new investigational drug (a monoclonal antibody) targeting the myostatin protein with the aim of improving muscle function. Its efficacy was evaluated in the phase III SAPPHIRE clinical trial.
Conducted across 48 hospitals in nine countries (including France), the trial involved 188 patients with type II or III SMA aged 2 to 21 years who were unable to walk independently. All were already receiving Spinraza or Evrysdi. A total of 128 participants received apitegromab (10 or 20 mg/kg) and 60 received a placebo every four weeks intravenously.
Further improving motor function
Over one year of follow-up, apitegromab showed a 1.8-point improvement in motor function (HFMSE motor scale) in participants aged 2 to 12 years who received it, whereas motor function declined over time in the placebo group despite treatment with Spinraza or Evrysdi.
This score evaluates the ability to perform activities such as sitting, rolling over, lying down, standing up, kneeling, lifting the head, standing, jumping or climbing stairs.
In addition, no serious treatment-related adverse events linked to the anti-myostatin therapy were reported, showing that the drug was well tolerated.
These results suggest that a treatment directly targeting muscle, combined with a treatment targeting the SMN protein, has the potential to provide additional motor benefit for patients.
At the end of the one-year treatment period, 98% of patients in the SAPPHIRE study agreed to continue participation in the ONYX trial, in which all participants receive apitegromab, in order to evaluate its longer-term efficacy.
Sources
Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE): a phase 3, double-blind, randomised, placebo-controlled trial
Crawford T, Servais S, Mercuri E.
Lancet Neurol. 2025 Sep.
A plain language summary of the SAPPHIRE clinical trial of apitegromab in children and young adults with spinal muscular atrophy
Crawford T, Servais S, Mercuri E.
Expert Rev Neurother. 2026 Jan.