Myostatin inhibitor ACE‐031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo‐controlled clinical trial

ABSTRACT Introduction : ACE‐031 is a fusion protein of activin receptor type IIB and IgG1‐Fc, which binds myostatin and related ligands. It aims to disrupt the inhibitory effect on muscle development and provide potential therapy for myopathies like Duchenne muscular dystrophy (DMD). Methods : ACE‐031 was administered subcutaneously every 2–4 weeks to DMD boys in a randomized, double‐blind, placebo‐controlled, ascending‐dose trial. The primary objective was safety evaluation. Secondary objectives included characterization of pharmacokinetics and pharmacodynamics. Results : ACE‐031 was not associated with serious or severe adverse events. The study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias. A trend for maintenance of the 6‐minute walk test (6MWT) distance in the ACE‐031 groups compared with a decline in the placebo group (not statistically significant) was noted, as was a trend for increased lean body mass and bone mineral density (BMD) and reduced fat mass. Conclusion : ACE‐031 use demonstrated trends for pharmacodynamic effects on lean mass, fat mass, BMD, and 6MWT. Non–muscle‐related adverse events contributed to the decision to discontinue the study. Myostatin inhibition is a promising therapeutic approach for DMD. Muscle Nerve 55 : 458–464, 2017