Treatment of sporadic inclusion body myositis with bimagrumab

Neurology. 2014 Dec 9;83(24):2239-46. doi: 10.1212/WNL.0000000000001070. Epub 2014 Nov 7.


Objective: To study activin signaling and its blockade in sporadic inclusion body myositis (sIBM) through translational studies and a randomized controlled trial.

Methods: We measured transforming growth factor β signaling by SMAD2/3 phosphorylation in muscle biopsies of 50 patients with neuromuscular disease (17 with sIBM). We tested inhibition of activin receptors IIA and IIB (ActRII) in 14 patients with sIBM using one dose of bimagrumab (n = 11) or placebo (n = 3). The primary outcome was the change in right thigh muscle volume by MRI at 8 weeks. Lean body mass, strength, and function were secondary outcomes. Twelve of the patients (10 bimagrumab, 2 placebo) participated in a subsequent 16-week observation phase.

Results: Muscle SMAD2/3 phosphorylation was higher in sIBM than in other muscle diseases studied (p = 0.003). Eight weeks after dosing, the bimagrumab-treated patients increased thigh muscle volume (right leg +6.5% compared with placebo, p = 0.024; left leg +7.6%, p = 0.009) and lean body mass (+5.7% compared with placebo, p = 0.014). Subsequently, bimagrumab-treated patients had improved 6-minute walking distance, which peaked at 16 weeks (+14.6%, p = 0.008) compared with placebo. There were no serious adverse events; the main adverse events with bimagrumab were mild acne and transient involuntary muscle contractions.

Conclusions: Transforming growth factor β superfamily signaling, at least through ActRII, is implicated in the pathophysiology of sIBM. Inhibition of ActRII increased muscle mass and function in this pilot trial, offering a potential novel treatment of sIBM.

Classification of evidence: This study provides Class I evidence that for patients with inclusion body myositis, bimagrumab increases thigh muscle volume at 8 weeks.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type II / antagonists & inhibitors
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Blocking
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Double-Blind Method
  • Exercise Test
  • Female
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Myositis, Inclusion Body / drug therapy*
  • Myositis, Inclusion Body / metabolism
  • Myositis, Inclusion Body / pathology
  • Neuromuscular Diseases / drug therapy
  • Neuromuscular Diseases / metabolism
  • Neuromuscular Diseases / pathology
  • Organ Size
  • Phosphorylation
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Thigh / pathology
  • Treatment Outcome


  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunologic Factors
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Activin Receptors, Type II
  • bimagrumab