Capricor Therapeutics' investigational cell therapy, CAP-1002, continues to show promise in slowing the decline of upper limb and heart function in patients with Duchenne muscular dystrophy (DMD). The two-year results from the HOPE-2 open label extension (OLE) study were presented at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, highlighting the potential of CAP-1002 as a disease-modifying therapy.
CAP-1002: A Potential Backbone Therapy for DMD
Mark Awadalla, vice president of clinical operations at Capricor Therapeutics, emphasized the potential of CAP-1002 to be used in conjunction with other DMD therapies, stating, "We really believe that CAP-1002 has the potential to be a backbone therapy, whether the patient is on exon-skipping, or [has] been exposed to gene therapy, or [is] just on steroids. We believe that CAP-1002 can be administered in conjunction with any therapy."
The ongoing pivotal Phase 3 HOPE-3 trial (NCT05126758) is currently recruiting males aged 10 and older with DMD across several U.S. sites. A data readout is anticipated this year, and positive results could pave the way for a regulatory application to the U.S. Food and Drug Administration (FDA).
Targeting Late-Stage DMD with CAP-1002
DMD is characterized by a deficiency in dystrophin, a protein crucial for muscle health. This deficiency leads to progressive muscle weakness and wasting, affecting both limb and heart muscles. Cardiomyopathy, or heart muscle disease, is a prevalent and often fatal complication in DMD patients. According to Awadalla, nearly all DMD patients develop cardiomyopathy by early adulthood, making it the leading cause of death in this population. Currently, there are no approved therapies specifically targeting heart disease in DMD patients.
CAP-1002 is composed of cardiosphere-derived cells sourced from healthy, donated heart muscle. Upon intravenous infusion, these cells release small vesicles that are taken up by target cells, including heart muscle cells. This process is believed to exert immunomodulatory, anti-inflammatory, and regenerative effects.
HOPE-2 Trial and Open Label Extension Results
The Phase 2 HOPE-2 clinical trial (NCT03406780) involved 20 boys and young men with relatively advanced DMD. Participants were randomized to receive either CAP-1002 infusions (150 million cells) or a placebo intravenously every three months for a year, while continuing their standard corticosteroid treatment. Results from the HOPE-2 trial demonstrated a significant 71% slowing of upper limb function decline in the CAP-1002 group compared to the placebo group, as measured by the Performance of the Upper Limb (PUL 1.2) scale. Furthermore, heart function, assessed by left ventricular ejection fraction (LVEF) on cardiac MRI, was preserved in the CAP-1002 group relative to placebo.
Following a gap period of approximately one year, 13 HOPE-2 participants enrolled in the OLE, where all received CAP-1002 treatment. The mean age of these patients was 13 years, and none were able to walk. After two years of treatment in the OLE, the mean decline in PUL 2.0 scores was approximately 2.8 points, regardless of initial treatment assignment in the main trial. This decline was significantly slower than the 7.7-point decline observed in the original placebo group during the two-year gap period when they were not receiving treatment (p=0.021). Overall, CAP-1002 was associated with a 64% slowing of disease progression.
Cardiac Function Improvements
Among nine patients with available cardiac MRI scans, six showed improvements in LVEF since the end of the main HOPE-2 trial. The average yearly increase in LVEF for these patients was 2.5%, a notable contrast to the natural history of DMD, where patients typically experience yearly declines of around 0.75%.
Awadalla emphasized the importance of early intervention, stating, "Time is muscle for these patients. CAP-1002 demonstrates the potential to slow disease progression."
The treatment has maintained a favorable safety profile throughout the analyses, reinforcing its potential as a valuable therapeutic option for DMD patients.
