BACKGROUND: Bimagrumab is a human monoclonal antibody inhibitor of activin type 
II receptors (ActRII), with anabolic action on skeletal muscle mass by blocking 
binding of myostatin and other negative regulators of muscle growth. Bimagrumab 
is under evaluation for muscle wasting and associated functional loss in hip 
fracture and sarcopenia, and in obesity. Bimagrumab also blocks other endogenous 
ActRII ligands, such as activins, which act on the neurohormonal axes, 
pituitary, gonads and adrenal glands.
AIM: To evaluate the effect of bimagrumab on the pituitary-gonadal and 
pituitary-adrenal axes in humans.
METHODS: Healthy men and women, aged 55 to 75 years, received bimagrumab 
intravenously 10 mg/kg or placebo on Day 1 and Day 29. Pituitary-gonadal and 
pituitary-adrenal functions were evaluated with basal hormone measurement and 
standard gonadotropin-releasing hormone (GnRH) and adrenocorticotropic hormone 
(ACTH) stimulation tests at baseline, Week 8 and at the end of study (EOS)-Week 
20.
RESULTS: At Week 8, follicle-stimulating hormone (FSH) levels were reduced by 
42.16 IU/L (P < .001) and luteinizing hormone (LH) levels were increased by 2.5 
IU/L (P = .08) over placebo in response to bimagrumab in women but not in men. 
Effects that were reversible after bimagrumab was cleared. Gonadal and adrenal 
androgen levels were not affected by exposure to bimagrumab.
CONCLUSION: Bimagrumab alters the function of pituitary gonadotroph cells, 
consistent with blockade of activin on local ActRII. This effect is reversible 
with clearance of bimagrumab. Bimagrumab did not impact gonadal and adrenal 
androgen secretion.