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.