Positive results from the Phase III SAPPHIRE trial with apitegromab in SMA

Apitegromab is a human monoclonal antibody that selectively inhibits myostatin activation to improve muscle function. Its efficacy was evaluated at one year in the Phase IIIAu cours d’un essai clinique de phase III, un médicament, pour lequel on a déterminé lors d’essais antérieurs l’innocuité et le dosage optimum (essais de phase I et II), est administré à un grand groupe de malades, sur une longue durée, dans le but d’évaluer son efficacité thérapeutique en la comparant à celle d’un traitement de référence ou un placebo. Il permet aussi de mettre en évidence les interactions indésirables et les effets secondaires du traitement à moyen terme. Au terme de cet essai, le médicament peut obtenir une autorisation de mise sur le marché. SAPPHIRE trial, which included 188 patients with type II or III SMA who were non-ambulatory, aged 2 to 21 years, and already receiving treatment targeting the SMN protein (Spinraza or Evrysdi). Of these, 128 received apitegromab and 60 received a placeboLe placebo est un produit dont la présentation est identique à celle d’un médicament, mais qui ne contient pas de principe actif. Dans un essai clinique, un placebo est utilisé pour mesurer l’action réelle du médicament testé, en comparant les effets du médicament testé contenant le principe actif et ceux du placebo..

• The trial was conducted in 48 hospitals in nine countries, including France, in Lille, Paris (I-Motion) and Toulouse.
• Participants aged 2 to 12 were randomly assigned to receive 10 or 20 mg/kg of apitegromab or a placebo. Those aged 13 to 21 were randomly assigned to receive 20 mg/kg of apitegromab or a placebo.
• At one year, participants receiving apitegromab showed an improvement in motor function on the HFMSE score (+1.8 points in those aged 2-12 years) compared to those receiving placebo, with an optimal dose of 10 mg/kg to stabilise or improve motor function in patients already receiving treatment for SMN.
• The HFMSE score decreased in patients receiving placebo.
• No serious adverse events were associated with apitegromab.
• After one year of follow-up, the ONYX extension phase took over, recruiting almost all participants (98%), all on apitegromab, to evaluate its long-term effects.

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.