Mesoblast Limited announced that the number of subjects treated in their ongoing Phase 3 clinical trial in chronic heart failure (CHF) that is testing their proprietary cell-based medicine MPC-150-IM will be substantially reduced.
CHF is characterized by an enlarged heart, coupled with insufficient blood supply to the organs and extremities of the body. Unfortunately, this is a progressing condition that tends to get worse with time. CHF is caused by many different factors such as chronic high blood pressure, faulty heart valves, infections, or congenital heart problems.
Mesoblast centers their company around the isolation and expansion of so-called mesenchymal precursor cells (MPCs) from bone marrow. Mesenchymal stem cells are found in many different tissues and organs throughout our bodies. They play vital roles in maintaining tissue health. However, relatively speaking, mesenchymal stem cells are rare cells. They are found around blood vessels and respond to signals associated with tissue damage. They secrete mediators and growth factors that promote tissue repair and control the immune response to prevent it from going out of control.
Mesoblast uses an array of monoclonal antibodies to isolate primitive mesenchymal stem cells that are actually precursors to mesenchymal stem cells or mesenchymal precursor cells (MPCs). These cells are then expanded in culture without being differentiated into any other cell type.
Mesoblasts, MPC-150-IM product consists of 150 million MPCs that are injected straight into the heart muscle (hence the moniker, “IM” for intramuscular). Once in the heart muscle, the MPCs induce the formation of new blood vessels to feed the heart muscle, stimulate resident stem cell populations in the heart to repair the heart muscle, and quell inflammation that can cause scarring and decrease heart function (see Yanping Cheng, et al., Cell Transplantation 22(12): 2299-2309; Jaco H. Houtgraaf, Circulation Research. 2013; 113: 153-166).
Initially, Mesoblast planned to test their product on 1,165 subjects, but have scaled that number back to approximately 600 patients.
Mesoblast’s development and commercial partner, Teva Pharmacueticals has communicated this reduction in the number of subjects to the US Food and Drug Administration (USFDA). “The reduction in the size of the Phase 3 trial may significantly shorten the time to trial completion,” said Mesoblast CEO Silviu Itescu.
The reduction in the number of patients was due to a proposed change in the primary endpoint of the trial. The revised primary endpoint is now a comparison of recurrent heart failure-related major adverse cardiovascular events (HF-MACE) between patients treated with Mesoblast’s MPC-150-IM cells and the control patients who were not treated with these cells.
Why the change in the primary endpoint? The reason lies in the success that MPC-150-IM cells had their Phase 2 clinical trial. In this trial, a single injection of MPC-150-IM cells successfully prevented HF-MACE over three years. This second, confirmatory study will be conducted in parallel with a patient population that has an identical clinical profile; approximately 600 of them using the same primary endpoint.
In the completed Phase 2 trial, patients treated with MPC-150-IM had no HF-MACE over 36 months of follow-up, compared with 11 HF-MACE in the control group. From this same clinical trial, of those patients who suffered from advanced heart failure (defined by baseline Left Ventricular Systolic Volume being greater than 100 milliliters), 71 percent of the controls (who received no cells) had at least on HF-MACE versus none of those who received a single injection of MPC-150-IM cells. As it turns out, this Phase 2 patient population closely resemble the patients being recruited in the Phase 3 trial.
“Patients with advanced heart failure continue to represent among the largest unmet medical needs, where existing therapies are inadequate and the economic burden is the greatest. The current Phase 3 trial targets this patient population, continues to recruit well across North America, and is now expanding to Europe,” said Itescu.