Texas Heart Institute Leads Stem Cell Treatment Breakthrough for Patients With Coronary Heart Disease and Heart Failure
Texas Heart Institute (THI) announced the ground breaking results of the second phase of a dose escalation study that evaluated Mesoblast Limited’s proprietary Mesenchymal Precursor Cells (MPCs) injected into the hearts of patients with coronary disease and heart failure. The consistent and positive effects of these unique stem cells injected into the hearts of patients with coronary disease and heart failure reveals the safety of allogeneic cell therapy and promises a transformative future in treating congestive heart failure.
This cell delivery strategy championed by lead investigator, Dr. Emerson C. Perin, Director, Research in Cardiovascular Medicine and Medical Director of the Stem Cell Center at Texas Heart Institute, Clinical Professor of Medicine at Baylor College of Medicine and McNair Scholar, offers a promising alternative to patients with advanced heart failure because of MPCs ability to induce heart muscle repair, stimulate new blood vessel growth, decrease cell death and reduce scar formation. The Phase II trial results have been published in a paper in the latest edition of Circulation Research, a peer-reviewed, high-impact journal of the American Heart Association, as an “online first” article ahead of full print.
Lead author and investigator Dr. Emerson C. Perin said, “The findings from this trial are very encouraging and suggest that a high-dose of Mesoblast’s allogeneic cell-based therapy may decrease major clinical events associated with progressive heart failure for at least three years, including repeated hospitalizations or death. This has the potential to be transformative for those with the most severe coronary heart disease and heart failure.”
In this six center Phase II trial, which included CHI St. Luke’s Health-Baylor St. Luke’s Medical Center in Houston, Texas, these unique cells were originally taken from the bone marrow of one healthy, youthful donor and, guided by a transendocardial 3D map, were injected into 60 patients with coronary heart disease and heart failure who had no other option for treatment. Through a three-year follow-up, the study revealed a significant decrease in long-term heart failure events such as cardiac death and re-hospitalization. In the article, entitled ‘A Phase II Dose-Escalation Study of Allogeneic Mesenchymal Precursor Cells in Patients With Ischemic or Non-Ischemic Heart Failure’, the authors concluded that high-dose allogeneic MPC treatment may reverse the enlargement of the heart that occurs with heart failure (remodelling) as well as reduce heart failure-related major adverse cardiovascular events (HF-MACE).
Key results of the trial were:
Primary Endpoint of Safety
• Transendocardial injections of allogeneic MPCs into the hearts of patients with either ischemic or non-ischemic heart failure due to left ventricular systolic dysfunction were feasible and safe, with a similar incidence of adverse events across all control and treatment groups.
• Treatment of patients with allogeneic MPCs was not associated with any clinically significant immune response.
Secondary Efficacy Endpoints
• Patients treated with the highest dose, MPC 150M, showed the greatest improvement compared to controls for left ventricular remodelling (Left Ventricular End Systolic Volume (LVESV) p=0.015 and Left Ventricular End Diastolic Volume (LVEDV) p=0.02) at month 6 post treatment.
• Parallel improvements in both LVESV and LVEDV in the MPC-treated groups may have accounted for the observed non-significant changes in ejection fraction.
• Patients treated with the highest dose, MPC 150M, showed the greatest improvement in functional exercise capacity compared to controls (6MTW: p=0.062) at month 12 post treatment.
Major Adverse Cardiovascular Events (MACE)
• In a post-hoc analysis after all patients had completed 36 months of follow up, treatment with MPC 150M was shown to be associated with a significantly lower incidence of HF-MACE events compared to the control group (0% vs 33% HF-MACE by Kaplan-Meier, p=0.026 by log-rank).
Dr. James T. Willerson, president of THI and co-author of the paper, elaborated on the results and the potential impact of the therapy, “This is a very important finding for patients with coronary heart disease and heart failure. The world-wide expansion of this trial will help to confirm these findings, but the early results demonstrate a real reason for optimism for the treatment’s potential use in future patients.”
Based on the results of the Phase II, the MPC trial is now leading the first and largest phase III trial of stem cells in heart failure, which could eventually lead to approval of cell therapy as a treatment for heart failure. DREAM-HF, the randomized, placebo-controlled Phase III trial, is being conducted by Teva Pharmaceutical Industries Ltd., will enroll 1700 patients worldwide and is actively enrolling patients across multiple clinical sites in North America. The primary efficacy endpoint for the Phase III trial is a time-to-first-event analysis of HF-MACE, the same efficacy endpoint achieved in the Phase II trial by the group receiving MPC 150M.
“These potentially transformative effects appear to be due to the ability of these cells to positively impact on adverse cardiac remodelling associated with chronic heart failure. If these results are confirmed in the ongoing Phase 3 trial currently recruiting at our institution and elsewhere, this new therapy has the potential to change the paradigm for the management of patients with advanced heart failure who are at high risk of hospitalization and death,” Perin added.
Texas Heart Stem Cell Center is a world leader in clinical cardiovascular stem cell research. Although investigating all aspects of cardiovascular disease, the center has particular leadership in advancing treatments for heart failure, having performed the first human stem cell treatment for heart failure in December 2001. Since 2001, Texas Heart Stem Cell Center has led 7 randomized controlled trials (nationally and internationally) of stem cell therapy for heart failure, gradually gaining critical understanding of cell therapy and exploring different cell types. The stem cell center is currently involved in 4 randomized cell therapy trials for heart failure. Two of these trials are associated with the NIH cell therapy network, which comprises 7 centers in the U.S. (CCTRN).