Results from a Phase 2 Study of ACE-083 in Patients with Facioscapulohumeral Muscular Dystrophy (FSHD) – Implications for Future Clinical Trials


Clinical Trials

Poster Number: 43


Jeffrey Statland, MD, Nicholas Johnson, MD, Anthony Amato, Cynthia Bodkin, Russell Butterfield, MD, PhD, Craig Campbell, Urvi Desai, Jordi Díaz-Manera, Lauren Elman, Josep Gamez, Angela Genge, Jeffrey Guptil, Nanette Joyce, Chafic Karam, MD, Lawrence Korngut, Georgios Manousakis, katherine Mathews, MD, Alan Pestronk, Perry Shieh, MD, PhD, Rabi Tawil, MD, Kathryn Wagner, MD, Matthew Wicklund, MD, Juan J Vilchez-Padilla, Ashley Leneus, Barry Miller, Marcie Fowler, PhD, Marc van de Rijn


1. University of Kansas Medical Center, 2. Virginia Commonwealth University, 3. Brigham and Women's Hospital, 4. Indiana University, 5. University of Utah, 6. Western University, London, ON, Canada, 7. Carolinas Healthcare System Neurosciences Institute, 8. Hospital de la Santa Creu i Sant Pau Barcelona, 9. University of Pennsylvania, 10. Hospital Universitario Vall d'Hebron, 11. Montreal Neurological Institute and Hospital, Montreal, Canada, 12. Duke University School of Medicine, 13. University of California Davis Medical Center, 14. Oregon Health and Science University, Portland, OR, USA, 15. University of Calgary, 16. University of Minnesota, 17. University of Iowa, 18. Washington University School of Medicine, 19. David Geffen School of Medicine at UCLA, 20. University of Rochester, 21. Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA, 22. University of Colorado , 23. Hospital Universitari i Politecnic La Fe, 24. Acceleron Pharma, 24. Acceleron Pharma, 25. Acceleron Pharma, 26. Acceleron Pharma

Background: ACE-083 is a locally acting muscle therapeutic based on follistatin that binds myostatin and other muscle regulators. ACE-083 has been shown to increase muscle mass of injected muscles in animal models, healthy subjects, and patients with FSHD or Charcot-Marie-Tooth (CMT) disease.

Objectives/Methods: The primary objectives were to determine if ACE-083 could safely increase total muscle volume (TMV) of the tibialis anterior (TA) or biceps brachii (BB) in patients with FSHD1 or 2. Part 1 was dose-ranging (N=37, previously reported); Part 2 was double-blind, placebo-controlled for 6 months followed by a 6-month open-label period. Patients were treated with ACE-083 240 mg/muscle or placebo (1:1) injected into the TA or BB bilaterally q3 weeks. Secondary endpoints included fat fraction (FF), strength, timed function tests, and quality of life (FSHD-Health Index, HI).

Results: We enrolled 58 patients (safety set) in Part 2 and 55 were evaluable for efficacy/PD endpoints. Median (range) baseline age (yr) was 46.0 (18-70) in TA cohorts, 46.0 (21-80) in BB cohorts. We saw mean (SEM) increases in TMV of 13.8% (2.9) for ACE-083 vs 4.3% (2.7) for placebo (p=0.01) in TA, and increases of 19.1% (2.8) for ACE-083 vs 2.7% (2.8) (p<0.0001) for placebo in BB. There were no statistically significant differences between ACE-083 and placebo groups for % change in 6-minute walk distance, 10m walk/run, 4-stair climb (TA) or Performance of Upper Limb (BB), nor for raw change in FSHD-HI scores. ACE-083 was generally well-tolerated; common adverse events included injection site reactions and myalgia.

Conclusions: Although ACE-083 demonstrated significant increases in mean TMV, there were no statistically significant improvements in other clinical outcome measures (COMs). Learning and placebo effects identified in some COMs support consideration of a run-in period and emphasize the importance of an appropriate comparator arm in neuromuscular studies.