Effects of bimagrumab, an activin receptor type II inhibitor, on pituitary neurohormonal axes

Summary Background Bimagrumab is a human monoclonal antibody inhibitor of activin type II receptors (Act RII ), 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 Act RII 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 (Gn RH ) 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 Act RII . This effect is reversible with clearance of bimagrumab. Bimagrumab did not impact gonadal and adrenal androgen secretion.