Mesoblast announced positive Phase 2 heart failure trial results of its off-the-shelf, adult stem cell product Revascor after all patients had completed a minimum follow-up of 12 months, and a mean follow-up of 22 months. The Phase 2 trial results were presented at the American Heart Association annual meeting in Orlando, Florida, by independent principal investigator Dr Emerson C. Perin, Director of Research in Cardiovascular Medicine and Medical Director, Stem Cell Center, Texas Heart Institute in Houston.
Mesenchymal Precursor Cells or MPCs are bone marrow stem cells that have none of the markers expressed by mature mesenchymal stem cells (MSCs), but they are the stem cells population that gives rise to mesenchymal stem cells. Therefore, they have the advantages of MSCs – such as they are not recognized by the immune system, but because they are not mature MSCs, they can differentiate into a far wider variety of cell types than mature MSCs.
MPC treatment in this trial pooled data from patients that received all different doses and these pooled data showed that patients who had received MPC treatments had a significant reduction in cardiac mortality. Furthermore, at the highest dose, the MPCs completely prevented heart failure hospitalization events. Mesoblast expects that these outcomes will be central to the primary endpoint of a Revascor Phase 3 trial for product regulatory approval by the United States Food and Drug Administration (FDA).
This phase II trial used a randomized, placebo-controlled 60-patient Phase 2 trial that compared the safety and efficacy of three doses of Revascor in addition to maximal approved therapies versus maximal therapies alone in patients with moderate-to-severe congestive heart failure (CHF) defined by New York Heart Association (NYHA) class II or III status and ejection fraction below 40%. The trial enrolled both ischemic and non-ischemic heart failure patients. Heart failure patients with this degree of severity are known to have a high cardiac mortality over a 12-24 month period despite being on maximal approved drug and device therapies.
Treatment with MPCs was well-tolerated. Over a 22-month mean follow-up period, only 1/45 (2%) patients who received a single injection of Revascor died of cardiac causes compared with 3/15 (20%) of the control group (p=0.02). In addition, MPC treatment significantly delayed the time to a first Major Adverse Cardiac Event, MACE, a composite of cardiac death, heart attack or revascularization procedures (p=0.036), and reduced the overall risk for MACE by 78% (p=0.011). Over a mean follow-up of 18 months, 0/15 patients who received the highest dose of MPC (150M) had been hospitalized for heart failure or had died. In contrast, 3/15 (20%) controls and 6/30 (20%) patients who received low (25M) or mid (75M) doses of MPC had either been hospitalized with heart failure or had died. This clinical improvement associated with the 150M dose was accompanied by evidence of cardiac remodeling (reduction in left ventricular end systolic volumes compared with controls at 6 months, p=0.015) and improved functional heart capacity (gain of 52.6 meters over 6 minutes’ walk compared with controls at 12 months, p=0.06).
After 12 months, 40% of all treated patients had reverted to class I NYHA status compared with 14% of all controls, and this effect remained when patients were matched for the presence of class II status at baseline. The group who received the 25M MPC dose showed a significant 8.9 point improvement in ejection fraction over controls at 3 months (p=0.008), with a sustained but less pronounced effect over 12 months. In contrast, the group who received 150M MPC did not show improved ejection fraction, suggesting that the positive effects of this dose on clinical outcomes, remodeling, and functional capacity may be due to other mechanisms such as anti-fibrosis.
Dr. Perin stated: “These clinical findings are the first using any cell therapy in heart failure patients to show a concordant positive effect on clinical outcomes, cardiac remodeling, and functional capacity, the three key parameters in congestive heart failure. Together, they indicate that a single 150 million dose of Revascor may significantly reduce both heart failure hospitalizations and death in these very sick patients who have such a poor prognosis despite maximal existing therapies. Based on their defined product characterization, batch to batch consistency, immediate availability, and lack of clinically relevant immunogenicity, MPCs appear to be an ideal cell type to provide a new level of patient care in congestive heart failure. We look forward to progressing the Revascor clinical program into Phase 3.”
Revascor is being jointly developed by Mesoblast and its strategic alliance partner, Teva Pharmaceutical Industries Ltd. Teva’s Corporate Vice President Global Branded Products, Kevin Buchi, said: “These independently-reviewed results serve to reinforce Teva’s commitment to its strategic investment in Mesoblast’s adult stem cell technology and to our continued support for the clinical development of Revascor.”
Mesoblast Chief Executive, Professor Silviu Itescu, said, “Together with our partners at Teva, we are deeply committed to bringing to market an effective cell therapy product to reduce recurrent hospitalization episodes and risk of death in patients with progressive heart failure. The exciting results presented at the American Heart Association meeting reinforce the strength of our technology and emphasize the need to maintain a rapid development path in order to make this product available for the many patients suffering with heart failure.”