Deramiocel Significantly Slows Upper Limb Functional Decline in Duchenne Muscular Dystrophy: Skeletal Muscle Outcomes from the Phase 3 HOPE-3 Trial
Susan Iannaccone1, Craig McDonald2, Aravindhan Veerapandiyan3, Arun Varadhachary4, Leigh Ramos-Platt5, Kathryn Gambetta6, Russell Butterfield7, Mindy Leffler8, kati maharry9, Nathaniel J. Hogan10, susan apkon11, Cuixia Tian12, Katherine Mathews13, Nancy Bass14, Chamindra Laverty15, Han Phan16, Partha Ghosh17, Seth Perlman18, Rebecca Scharf19, Kathryn mosher20, Saunder Bernes21, Jane emerson22, Edward Smith23, Michael Binks9, Mark Awadalla9, Linda Marban24
1Department of Pediatrics, 2UC Davis Dept. of PM&R, 3Arkansas Childrens Hospital/UAMS, 4Washington University in St Louis, 5USC/Children'S Hospital of Los Angeles, 6Ann & Robert H. Lurie Children’s Hospital of Chicago, 7University of Utah, 8Consultant, 9Capricor Therapeutics Inc, 10Capricor Therapeutics Inc., 11Children's Hospital Colorado, 12Cincinnati Childrens Hospital Medical Center, 13University of Iowa - Dept of Pediatrics, 14Children's Wisconsin, 15UC San Diego, 16Rare Disease Research, LLC, 17Boston Children'S Hospital, 18Seattle Children's Hospital, 19University of Virginia Children’s Hospital, 20Akron Children's Hospital, 21Phoenix Childrens Hospital, 22University of Missouri School of Medicine, Columbia, 23Rare Disease Research - NC, LLC, 24capricor Therapeutics Inc
Objective:
Confirmation of musculoskeletal efficacy of deramiocel in DMD using clinic and home-based assessments
Background:
Deramiocel is a novel cellular therapy previously shown to benefit skeletal muscle function in Duchenne muscular dystrophy (DMD) in a phase 2 randomized placebo-controlled trial. The mechanism is pleiotropic, likely involving extracellular vesicles and soluble factors that confer immune-modulatory, anti-inflammatory, and anti-fibrotic properties. This phase-3 study assessed efficacy and safety of deramiocel in late-ambulatory and non-ambulatory DMD subjects.
Design/Methods:
HOPE-3 was a randomized, double-blind, placebo-controlled Phase 3 study enrolling 106 patients with DMD. The primary endpoint was mean percent change from baseline in the Performance of Upper Limb (PUL2.0) Total Score at Month 12. Secondary endpoints included the PUL 2.0 mid-level domain and the Duchenne Video Assessment (DVA) score of Eating 10 Bites, a measure of sustained feeding performance in the home environment, blinded to timepoint.
Results:
At Month 12, mean percent change from baseline in PUL2.0 Total Score was −3.86 in the deramiocel group versus −8.41 in the placebo group, a difference of 4.55 (p = 0.029) which corresponds to 54% slowing of disease progression over 12 months. Mid-level PUL2.0, function closely related to independence, differed by 8.12 (p = 0.008), a 60% slowing of progression. Deramiocel also significantly reduced deterioration in independent feeding as measured by the Eat 10 Bites score at 12 months (p = 0.0176) for which data were available on 90 patients. Deramiocel was safe and well tolerated.
Conclusions:
Treatment with deramiocel resulted in a clinically meaningful and statistically significant slowing of upper limb disease progression over 12 months. The magnitude of effect, concordance across standardized functional scales and home-based real-world video assessments support deramiocel as a therapy with the potential to modify the course of skeletal muscle decline and preserve independent function in patients with DMD.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.