Apitegromab, a monoclonal antibody against promyostatin and latent myostatin can inhibit the activation of promyostatin in vitro, confirmed a new study published in the International Journal of Toxicology.

Moreover, studies in monkeys and rats showed that weekly intravenous administration of apitegromab was well-tolerated, with no treatment-related adverse effects, and led to sustained serum exposure and target engagement. Finally, no adverse effects on neurodevelopmental, motor, or reproductive outcomes were recorded in juvenile rats.

These findings support the development of apitegromab as a potential new therapeutic option for muscle atrophying diseases such as spinal muscular atrophy (SMA). 

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“The nonclinical pharmacology, pharmacokinetic, and toxicology data demonstrate that apitegromab is a selective inhibitor of proforms of myostatin that does not exhibit toxicities observed with other myostatin pathway inhibitors,” wrote Brian T. Welsh, PhD, and the co-authors of the study. They added that their data “support the conduct of ongoing clinical studies of apitegromab in adult and pediatric patients with spinal muscular atrophy (SMA)”.

Read more about SMA experimental therapies

Myostatin is a protein that inhibits muscle cell growth. Therefore, it has been a therapeutic target for muscle atrophying diseases such as Becker muscular dystrophy, Duchenne muscular dystrophy, and SMA. However, even though experiments in animal models have yielded positive results, the success of myostatin inhibition has been limited in the clinic possibly due to the lack of specificity of the inhibitors used. 

Apitegromab is a fully human, monoclonal antibody that specifically binds to human promyostatin and latent myostatin inhibiting myostatin activation. It does not bind to mature myostatin or other growth factors that are closely related. 

Apitegromab is already being tested in an ongoing phase 2 clinical trial in patients with type 2 or type 3 SMA, who are aged 2 to 21 years, to evaluate its safety and efficacy.

The data reported in the present study support the ongoing clinical exploration of apitegromab in patients with SMA. 


Welsh BT, Cote SM, Meshulam D, et al. Preclinical safety assessment and toxicokinetics of apitegromab, an antibody targeting proforms of myostatin for the treatment of muscle-atrophying disease. Int J Toxicol. 2021;40(4):322-336. doi:10.1177/10915818211025477

An active treatment study of SRK-015 in patients with type 2 or type 3 spinal muscular atrophy (TOPAZ). US National Library of Medicine. Last updated June 18, 2021. Accessed July 26, 2021.