Capricor Therapeutics said it would have to cut jobs and the scope of its operations after interim data from a Phase II study evaluating its lead allogeneic cardiosphere-derived cell therapy CAP-1002 in heart attack patients showed that the trial was unlikely to meet its primary 12-month efficacy endpoint. The firm said it would now focus its resources on its Duchenne muscular dystrophy (DMD) program for CAP-1002.
The 142-patient ALLSTAR trial was evaluating CAP-1002 in adults who have experienced a large heart attack with residual cardiac dysfunction. The prespecified interim analysis on 6 months of follow-up data indicated that the study wasn’t going to demonstrate a statistically significant difference in the efficacy endpoint of percent change from baseline infarct size as a percentage of left ventricular mass, measured by cardiac magnetic resonance imaging (MRI).
“The lack of a clear difference in the change in scar size from baseline to 6 months between the active and control groups in the interim observations from ALLSTAR was unexpected,” admitted Linda Marbán, Ph.D., president and CEO of Capricor. “These results diverge from the consistent and extensive record of activity observed with our cell technology in the setting of cardiac fibrosis as demonstrated by both preclinical and clinical studies, and we hope to gain an understanding of the factors that led to these observations through the conduct of further analyses.”
Raj Makkar, M.D., co-principal investigator of the ALLSTAR Trial, and associate director for interventional technologies in the Heart Institute at Cedars-Sinai Medical Center, added, “We believe it is important to note that the observed improvements in scar size in the placebo group are markedly inconsistent with the well-established natural history of this disease process. It is certainly possible that, for a variety of reasons, the greater number of sites involved in the conduct of ALLSTAR contributed to an increase in variability seen in the scar measurements as determined by MRI.”
Carpricor said it would continue to analyze cumulative ALLSTAR data, which showed no notable differences between treatment groups in ejection fraction, but did show near statistically significant reductions in mean end-diastolic volume and trends toward reduction in mean end-systolic volume associated with CAP-1002 therapy.
The firm hasn’t disclosed how many jobs will have to go, but said it would now concentrate on developing CAP-1002 for the DMD indication, including the ongoing Phase I/II HOPE trial evaluating skeletal muscle performance and cardiac biomarkers in boys and young men with DMD treated using CAP-1002. Positive 6-month data from the single-dose HOPE study were reported last month.
Capricor also plans to start a repeated-dose study with intravenous CAP-1002 therapy in DMD during the second half of 2017, primarily to evaluate skeletal (noncardiac) muscle function.
“Although we are disappointed, the favorable safety profile demonstrated by CAP-1002 in ALLSTAR supports the prospect of its chronic, repeat administration in patients with DMD,” Dr. Marbán added. “Also, the potent anti-inflammatory properties of CAP-1002 may be well-suited to mitigate DMD progression, for which chronic inflammation is believed to play a causative role.”
Earlier this week Capricor confirmed raising $3.7 million in a private placement, which the firm said it would use to progress its products and for general corporate purposes. In February, Capricor reported that it was dropping its Phase II-stage heart failure drug Cenderitide and would end its license agreement with the Mayo Clinic for the natriuretic peptide receptor agonist program so that it could concentrate on its cell- and exosome-based programs.