LB: Confirmation of musculoskeletal and cardiac benefit in DMD from deramiocel, an allogeneic cell therapy, in the Phase 3 HOPE-3 study

Topic:

Clinical Trials

Poster Number: 479 LBT

Author(s):

Craig McDonald, MD, UC Davis, Chet Villa, MD, Cincinnati Children’s Hospital Medical Center, Jonathon H Soslow, MD, Vanderbilt University Medical Center, Michael Binks, MD, Capricor, Kati Maharry, PhD, Capricor Therapeutics Inc, Nathaniel Hogan, PhD, Capricor Therapeutics Inc, Kevin Barth, BS, Capricor Therapeutics Inc, Erik Hendricson, PhD, UC Davis, Cuixia Tian, MD, Cincinnati Children’s Hospital Medical Center, Han Phan, MD, Rare Disease Research, Atlanta, Georgia, USA, Susan Apkon, Children’s Hospital Colorado, Partha S. Ghosh, MD, Boston Children's Hospital, Aravindhan Veerapandiyan, MD, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, US, Leigh Ramos-Platt, MD, Children’s Hospital Los Angeles, Katheryn Gambetta, MD, Children's Hospital of Chicago, Saunder Bernes, MD, Phoenix Children’s Hospital, Arun Varadhachary, MD, PhD, Washington University School of Medicine, Susan T. Iannaccone, MD, UT Southwestern, Chamindra Laverty, MD, UC San Diego Health, Seth J. Perlman, MD, Seattle Children's, Nancy E. Bass, MD, Children's Wisconsin, Kathryn Mosher, MD, Akron Children's Hospital, Katherine Mathews, MD, University of Iowa, Iowa City, Iowa, USA, Rebecca J. Scharf, MD, MPH, University of Virginia (UVA) Children’s Hospital, Edward C. Smith, MD, Rare Disease Research North Carolina, Jane Anne Emerson, MD, University of Missouri School of Medicine, Russell J. Butterfield, MD, PhD, University of Utah, Kan Hor, MD, Nationwide Children's Hospital, Michael Taylor, MD,PhD, UT Austin, Mark Awadalla, BS, Capricor, Linda Marban, PhD, Capricor

Background
Deramiocel is a novel cellular therapy previously shown to benefit skeletal muscle and cardiac 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.

Methods
HOPE-3, a phase 3 multicenter, randomized double-blind, placebo-controlled study enrolled DMD participants aged ≥10 years. Deramiocel (1.5×108 cells) or placebo was administered by IV infusion over 60-90 minutes every 3 months. All endpoints were evaluated as placebo adjusted change from baseline at 12 months. The primary efficacy endpoint was percent change in total Performance of Upper Limb (PUL2.0) score and key secondary was rank change in left ventricular ejection fraction (LVEF) by cardiac MRI (CMR). Other type-1 error controlled secondary endpoints included mid-level PUL2.0, a global statistical test (GST) and late gadolinium enhancement (LGE) by CMR.

Results
The intent to treat population (n=106) was well-balanced at baseline. All type-1 error controlled primary and secondary endpoints demonstrated statistically significant benefit for deramiocel over placebo. For PUL2.0 score the difference from placebo was 4.55% (95% CI 0.47-8.63; p=0.029) for total and 8.12% (p=0.008) for mid-level. For LVEF, the rank change difference was 11.65 (p=0.041) which corresponds to an absolute difference in LVEF of 2.4%. Statistically significant differences were also achieved with GST and LGE. Treatment with deramiocel was well tolerated with no imbalance of severe or serious adverse events compared to placebo.

Conclusions
Deramiocel significantly slows DMD upper limb and cardiac progression with a favorable safety profile. These findings support deramiocel as a clinically effective novel DMD therapeutic.