CAP-1002, an Allogeneic Cell Therapy Demonstrates Disease Modification in Later-Stage DMD Patients: 18-Month Results from the HOPE-2-Open Label Extens


Clinical Trials

Poster Number: 163


Linda Marban, PhD, Capricor Therapeutics, Craig M. McDonald, M.D.,, M.d, University of California at Davis (USA), Suzanne Hendrix,, Ph.D.,, Pentara Corporation, Matthew M. Harmelink, M.D, Medical College of Wisconsin., Arun S. Varadhachary,, M.D, Barnes-Jewish Hospital, Cuixia Tian, M.D, CCHMC, Michelle Eagle,, Ph.D, Atom International Ltd (UK), Linda Marban, Ph.D,, Susan Apkon,, M.D.,, Children's Hospital Colorado

CAP-1002, an investigational cell therapy product, has shown promising clinical outcomes for the treatment of Duchenne muscular dystrophy (DMD) in multiple clinical trials. In the randomized, double-blind and placebo-controlled HOPE-2 clinical trial, CAP 1002 versus placebo was investigated in 20 DMD subjects demonstrating disease stabilization in both cardiac and skeletal muscle function in primarily non-ambulant DMD patients. 13 patients (CAP-1002: n=6; placebo: n=7) entered a subsequent open-label extension study (HOPE-2-OLE) where all patients received CAP-1002 with 12 having completed an 18-month follow-up. Importantly, subjects were off treatment for approximately one year following completion of HOPE-2 (“Gap Phase”) allowing for evaluation of patients both on- and off-treatment.
The 18-month analysis for performance of upper limb (PUL v2.0) further strengthened the previously reported results from HOPE-2. Significant differences were observed for subjects in HOPE-2-OLE compared with the placebo subjects in HOPE-2 (Δ=2.78 points (with 18 month OLE scaled to 12 months), p=0.0021) and in the Gap Phase (Δ=3.34 points (with 18 month OLE scaled to 12 months), p=0.0008). Disease progression slowed significantly in the original HOPE-2 placebo group after starting CAP-1002, resulting in a decreased between-group difference than observed in the HOPE-2 trial. The mean change from baseline in HOPE-2-OLE is comparable to that in the HOPE-2 CAP-1002 group and is significantly different from that in the HOPE-2 placebo group.
Data from HOPE-2 and the OLE suggested that CAP-1002 slows upper limb functional decline in DMD by modifying disease. The significant difference in PUL v2.0 scores between groups (CAP-1002 vs. placebo) in HOPE-2 (p=0.0059) was maintained in the Gap Phase (p=0.0017 without baseline covariate). Additionally, a non-inferiority analysis of disease progression slopes in the Gap Phase showed no convergence. All statistical inference is based on an MMRM assuming spatial power law covariance structure.
CAP-1002 was well tolerated without new safety signals identified in HOPE-2-OLE. CAP-1002 demonstrates novel, clinically meaningful, and cumulative preservation of upper limb function by potentially modifying the underlying disease.