Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy

Jeffrey M. Statland, Craig Campbell, Urvi Desai, Chafic Karam, Jordi Díaz-Manera, Jeffrey T. Guptill, Lawrence Korngut, Angela Genge, Rabi N. Tawil, Lauren Elman, Nanette C. Joyce, Kathryn R. Wagner, Georgios Manousakis, Anthony A. Amato, Russell J. Butterfield, Perry B. Shieh, Matthew Wicklund, Josep Gamez, Cynthia Bodkin, Alan PestronkConrad C. Weihl, Juan J. Vilchez-Padilla, Nicholas E. Johnson, Katherine D. Mathews, Barry Miller, Ashley Leneus, Marcie Fowler, Marc van de Rijn, Kenneth M. Attie

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


INTRODUCTION/AIMS: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD.

METHODS: Participants were at least 18 years old and had FSHD1/FSHD2. Part 1 was open label, ascending dose, assessing safety and tolerability (primary objective). Part 2 was randomized, double-blind for 6 months, evaluating ACE-083240 mg/muscle vs placebo injected bilaterally every 3 weeks in the biceps brachii (BB) or tibialis anterior (TA) muscles, followed by 6 months of open label. Magnetic resonance imaging measures included total muscle volume (TMV; primary objective), fat fraction (FF), and contractile muscle volume (CMV). Functional measures included 6-minute walk test, 10-meter walk/run, and 4-stair climb (TA group), and performance of upper limb midlevel/elbow score (BB group). Strength, patient-reported outcomes (PROs), and safety were also evaluated.

RESULTS: Parts 1 and 2 enrolled 37 and 58 participants, respectively. Among 55 participants evaluable in Part 2, the least-squares mean (90% confidence interval, analysis of covariance) treatment difference for TMV was 16.4% (9.8%-23.0%) in the BB group (P < .0001) and 9.5% (3.2%-15.9%) in the TA group (P = .01). CMV increased significantly in the BB and TA groups and FF decreased in the TA group. There were no consistent improvements in functional or PRO measures in either group. The most common adverse events were mild or moderate injection-site reactions.

DISCUSSION: Significant increases in TMV with ACE-083 vs placebo did not result in consistent functional or PRO improvements with up to 12 months of treatment.

Original languageEnglish (US)
Pages (from-to)50-62
Number of pages13
JournalMuscle and Nerve
Issue number1
StatePublished - Jul 2022

Bibliographical note

Funding Information:
J.M. Statland received grant support from the NIH, MDA, FSHD Society, and the Friends of FSH Research; he is a consultant or has served on advisory boards for Dyne, Fulcrum, Acceleron, Avidity, Strongbridge, Sarepta, and Genzyme. U. Desai has served on advisory boards for Alexion, CSL Behring, Argenx, Akcea, and Stealth Biotherapeutics and has served on the speaker's bureau for Alexion. C. Karam has undertaken consulting or educational activities for Akcea, Alexion, Alnylam, Argenx, Biogen, CSL Behring, Medscape, and Sanofi Genzyme and has received research grants from Sanofi Genzyme and Akcea. J. Díaz‐Manera has served as a consultant or on advisory boards for Sanofi‐Genzyme, Amicus, Audentes, Sarepta, and Spark. He has also received industry grant support from Sanofi Genzyme and Boehringer Ingelheim. J.T. Guptill has served as a consultant or on advisory boards for Immunovant, Alexion, Momenta, Ra Pharma, Grifols, Argenx, Jacobus, Becton Dickinson, Cabaletta, Regeneron, and Piedmont Pharmaceuticals and receives industry grant support from UCB for a fellowship training grant. A. Genge serves as a consultant for Mitsubishi Tanabe Pharma America, Sanofi Genzyme, AL‐S Pharma, AB Sciences, Biogen, Novartis, CSL Behring, Anavex, AveXis, Alexion, Wave Life Sciences, Revalesio, Roche, Cytokinetics, Orion, Akcea, Clene, Bayshore, and QurAlis. She participates as CRU Medical Director, PI, or sub‐PI on trials sponsored by AB Sciences, AL‐S Pharma, Acceleron, Amicus, Alnylam, Bioblast, Biogen, BMS, Boston Biomedical Cytokinetics, Sanofi Genzyme, Grifols, Ionis, Eli Lilly, Mallinckrodt, MedImmune, Novartis, Orion, Orphazyme, Pfizer, Ra Pharmaceuticals, Roche, Teva, and UCB. R.N. Tawil serves as an advisory board member or consultant for Acceleron Pharma, Fulcrum Therapeutics, MT Pharma, and Arrowhead Pharma. L. Elman has served on advisory boards for Roche/Genentech and Biogen and received royalties from (Wolters Kluwer). K.R. Wagner has served on advisory boards or consulted for AskBio, Dyne, Arrowhead Pharma, Catabasis, Santhera, and Vita. G. Manousakis has served on advisory boards for Stealth Biotherapeutics and Argenx. A.A. Amato is an associate editor for and has served as a medical consultant or on advisory boards for Sarepta, Alexion, and Serono; he received royalties from (Wolters Kluwer) and , . R.J. Butterfield is receiving funding via contracts for clinical trials from AveXis, PTC Therapeutics, Sarepta Therapeutics, Pfizer, Biogen, Capricorn, and Catabasis; he serves on scientific advisory boards for Sarepta Therapeutics, Biogen, AveXis, and Pfizer. M. Wicklund has received research funding from the NIH, MDA, Acceleron, Alexion, Baxalta, ML Bio, Orphazyme, and Sarepta Therapeutics and has served on advisory boards or in consultation for Affinia, Amicus, ML Bio, Sanofi, and Sarepta. J. Gamez has received grant funding from Fondo de Investigación Sanitaria (FIS‐FEDER) (grants PI16/01673 and PI19/00593). N.E. Johnson has received grant funding from the NINDS (4K23NS091511; R01NS104010), CDC (DD19‐002), and the FDA (7R01FD006071‐02); he receives royalties from the Congenital and Childhood Onset Myotonic Dystrophy Health Index and the Charcot‐Marie‐Tooth Health Index; receives research funds from Dyne, AveXis, CSL Behring, Vertex Pharmaceuticals, Fulcrum Therapeutics, ML Bio, Sarepta, and Acceleron Pharma; and has provided consultation for AveXis, AMO Pharma, Strongbridge BioPharma, Acceleron Pharma, Fulcrum Therapeutics, Dyne, Avidity, and Vertex Pharmaceuticals. B. Miller, A. Leneus, M. Fowler, M. van de Rijn, and K. Attie were employed by Acceleron Pharma during the study and had stock ownership and/or options. The remaining authors declare no conflicts of interest. UpToDate Neurology UpToDate Harrison's Principles of Internal Medicine Neuromuscular Disorders, 2nd ed

Funding Information:
Preliminary results from this study were presented at the 70th Annual American Academy of Neurology Meeting, April 2018, Los Angeles, California; the 23rd International Annual Congress of the World Muscle Society, February 2018, Mendoza, Argentina; and the Muscular Dystrophy Association Clinical & Scientific Congress, April 2019, Orlando, Florida. The authors thank the participants and their families for their participation and contributions, as well as the following team members: subinvestigators: Jorge Alonso-Pérez, MD, Richard Barohn, MD, Elena Bravver, MD, Benjamin Brooks, MD, Nizar Chahin, MD, Adam Comer, MD, Mazen Dimachkie, MD, Stacy Dixon, MD, PhD, Christopher Doughty, MD, Miriam Freimer, MD, Melanie Glenn, MD, Stanley Iyadurai, MD, Omar Jawdat, MD, Vern Juel, MD, Doris Leung, MD, PhD, Eric Logigian, MD, Samantha LoRusso, MD, Craig McDonald, MD, Nuria Muelas, MD, PhD, Erin O'Ferrall, MD, Mamatha Pasnoor, MD, Colin Quinn, MD, Rodney Li Pi Shan, MD, Amro Shino, MD, Francy Shu, MD, Joana Turon, MD, Lisa Hobson-Webb, MD, Eugenio Zapata, MD; evaluators: Anabel Alba, Melissa Currence, Lujan Diago, Xi Dong, Lauren Draper, Katy Eichinger, Keegan Fitzgerald, Julaine Florence, Patricia Flynn, Carme García-Fernández, Molly Grames, Laura Herbelin, Scott Holsten, Andrea Jaworek, Brandi Johnson, Laura Juel, Renee King, Wendy Koesters, Jose Martinez, Melissa McIntyre, Angela Micheels, Elena Montiel-Morillo, Alina Nicorici, Crystal O'Conner, Stephanie Poelker, Mohammed Sanjak, Cheryl Scholtes, Catherine Siener, Christy Skura, Nikia Stinson, Amelia Wilson; clinical site coordinators: Colleen Anthonisen, Genila Bibat, Natalya Burlakova, Megan Christ, Bryant Gordon, Sandy Guingrich, Shivali Gupta, Bridget Hoskins, Kianoush Kamali, Cynthia Lary, Leann Lewis, Jennifer Mabry, Pilar Marti, Ayla McCalley, Sterling Meisner, Kelsey Moulton, Alison Newell-Sturdivant, Jennifer Petzke, Lisa Ranzinger, Kristen Roe, Linda Schimoeller, Nikita Shah, Katherine Summerton, Alexa Vareldzis, Nuria Vidal-Fernández, Mary Yep. Medpace: Emily Birkmeyer, Shanshan Cui, Megan Kolthoff, Chad Leslie, Taylor Meece, Stephanie Porter, Georgiana Salyers, Richard Scheyer, MD, Wendy van den Branden, Alexa Vareldzis, Nuria Vidal; Acceleron: Bronwyn Owens, Barbara Leibo, Balasubrahmanyam Budda, SaraBeth Hahn, Jade Sun, Saba Qamar, Amelia Pearsall, Carrie Barron, Joseph Reynolds, Shuree Harrison, Josh Black, Matthew Sherman, Chad Glasser, VirtualScopics, VirtuSense, ATOM, University of Rochester (Chad Heatwole), ERT; editorial assistance (including incorporation of authors' edits and preparation of tables and figures based on the clinical study report): Joshua Ziel, PhD, Lisa Baker, PhD (Cadent Medical Communications, LLC, a Syneos Health group company), in accordance with Good Publication Practice principles and was supported by Acceleron Pharma.

Publisher Copyright:
© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.


  • FSHD
  • controlled trial
  • facioscapulohumeral muscular dystrophy
  • randomized
  • Magnetic Resonance Imaging
  • Muscle Contraction
  • Humans
  • Adolescent
  • Adult
  • Muscle, Skeletal
  • Muscular Dystrophy, Facioscapulohumeral
  • Cytomegalovirus Infections/pathology

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Randomized Controlled Trial
  • Clinical Trial, Phase II
  • Journal Article


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