NIH and Mesoblast Partner for Clinical Trial in End-Stage Heart Failure

Mesoblast Limited has partnered with the National Heart, Lung, and Blood Institute (a branch of the National Institutes of Health or NIH) to conduct a large clinical trial that uses Mesoblast’s proprietary adult stem cell treatment in patients with advanced heart failure that requires an implantable Left Ventricular Assist Device (LVAD) to maintain proper circulatory support. The Canadian Institutes for Health Research and the National Institute of Neurological Disease and Stroke are also supporters of this trial.

Mesoblast is an Australian company whose Mesenchymal Precursor Cells (MPCs) have shown some promise in several pre-clinical studies and a few small clinical trials. The main objective in this study is to use the MPCs in heart failure patients and to examine the ability of MPCs to reduce the need for LVADs. Also, the study will ascertain is MPCs reduce long-term complications of LVAD transplantation, the most common of which is repeated hospitalizations.

This 120-patient study, to be conducted by the NIH-funded Cardiovascular Surgical Trials Network, will evaluate the effects of MPC transplantation into the hearts of patients with advanced heart failure. 150 million MPCs will be injected into the hearts of each patient and this product is being tested as an “off-the-shelf” medical product.

This new clinical trial builds upon previous successful but small trials in which 30 heart patients were treated with either 25 million MPCs or MPC culture medium during LVAD implantation. This was a double-blind, placebo-controlled study, and it showed that the MPC-treated patients tended to show higher rates of not needing their LVADs anymore 90 days after implantation and 12 months after implantation. This study was complicated by the fact that several patients died during the trial, which is not surprising because patients who received LVADs tend to be very sick. Nevertheless, these results were suggestive that the MPCs were effective. This study was published in the journal Circulation, which is an American Heart Association publication.

This second study will examine 150 patients who will receive a higher dose of the MPCs and a phase three study is on the board in collaboration with Teva Pharmaceutical Industries Ltd, which is Mesoblast’s development and commercial partner, which will examine 1,700 patients.

One of the first measurements examined in this study is how long after the treatment until the patient experiences their first adverse heart event. These are called HF-MACEs or heart failure-related major adverse cardiac events. If MPCs delay the onset of the patient’s first HF-MACE, then the cells might be making the heart healthier and stronger.

Congestive heart failure is a chronic condition characterized by an enlarger heart and insufficient blood flow to the organs and extremities of the body. According to the American Heart Association, congestive heart failure affected ~5.1 million people 20 years of age or older in the US in 2010, and there are 825,000 new cases diagnosed annually. 50% of heart failure patients die within five years of diagnosis.

30%-40% of heart failure patients suffer from moderate/severe class II/III heart failure with low ejection fractions and 10% have advanced heart failure (NYHA class IV heart failure). the only treatment options for end-stage or class IV heart failure are a heart transplant or mechanical support with a LVAD. Heart transplants cannot meet the large need due to donor availability, and permanent LVAD support is currently limited by clinical complications.