Myostatin Inhibitor ACE-031 Treatment of Ambulatory Boys with Duchenne Muscular Dystrophy: Results of a randomized, placebo-controlled clinical trial

Authors

Craig Campbell, University of Western OntarioFollow
Hugh J McMillan, University of Ottawa
Jean K Mah, University of Calgary
Mark Tarnopolsky, McMaster University
Kathryn Selby, University of British Columbia
Ty McClure, Acceleron Pharma
Dawn M Wilson, Acceleron Pharma
Matthew L Sherman, Acceleron Pharma
Diana Escolar, Johns Hopkins Medical School
Kenneth M Attie, Acceleron Pharma

Document Type

Article

Publication Date

4-2017

Journal

Muscle & Nerve

Volume

55

Issue

4

First Page

458

Last Page

464

URL with Digital Object Identifier

https://doi.org/10.1002/mus.25268

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.