CAREMI - First-in-human clinical trial phase using multipotent cardiac cells to treat acute myocardial infraction was completed with success
The first results were recently presented of a study to evaluate clinical use of multipotent cells isolated from donor hearts (multipotent cardiac cells, CMC) to treat acute myocardial infarction. Launch of the second study phase has now been announced by the coordinator of the CAREMI project (Cardio Repair European Multidisciplinary Initiative), Dr. Antonio Bernad – Research Professor at the Centro Nacional de Biotecnología of the CSIC (CNB-CSIC) and Director of the BUC Campus of Excellence Program UAM+CSIC. This new phase will add 49 patients to the six already treated, who to date have shown "no adverse effects".
Acute myocardial infarction is one of the major challenges facing health care systems in developed countries. Although prompt, effective treatment has considerably reduced mortality, infarction is responsible for a large proportion of cases of chronic cardiac insufficiency. Its treatment, despite recent advances, remains a serious problem and requires approaches that bring together and coordinate experts from many fields.
In the last five years, CAREMI has developed a new approach to limit tissue damage caused by infarction, based on the activation of the heart’s natural repair mechanisms in response to damage. The project, coordinated through the Centro Nacional de Investigaciones Cardiovasculares (CNIC) by Dr. Bernad, is funded by the European Commission with a total budget of €11.3 M, of which more than €3 M have been invested in the project’s main objective, development of the clinical trial.
The product developed is allogeneic (not the patient's own) CMC, which are administered easily and safely via the intracoronary route. Using this scheme, the medical team has validated batches of CMC at its disposal, for use when they will be most therapeutically effective. Preclinical results indicate that CMC administration during the first week post-infarction, once the clinical situation has stabilized, promotes major cardiac regeneration. In parallel, the CAREMI consortium is developing complementary therapies that include generation of microparticles loaded with therapeutic molecules that can act on cardiac tissue.
CAREMI comprises renowned specialists in various basic research, preclinical and medical disciplines, and boasts an outstanding contribution by several Spanish research groups and organizations. The biotechnology company Coretherapix (Madrid), of the Genetrix Group, promoted this initiative and leads the technical and logistic development of the clinical trial and preclinical evaluation. The Centro de Cirugía de Mínima Invasión Jesús Usón (Cáceres) developed validation procedures in large animals. Two Spanish companies, Vivotecnia (Madrid) and Farmacros (Albacete), collaborated in biosafety and biodistribution studies in distinct phases of the project, and a third, 3P Biopharmaceuticals (Pamplona), produced the clinical quality CMC. The CNIC/CNB research centers, together with iBET - Instituto de Biologia Experimental e Tecnológica (IBET, Oeiras) and Coretherapix, carried out exhaustive molecular and cellular characterization of the human CMC population, their response to various stimuli, as well as characterization of the equivalent mouse cell populations. Characterization of the potential immune response to administered CMC was conducted by the Saint Louis Hospital in Paris, an international reference center in this field. Finally, the development of active monospheres is led by the Dutch companies Innocore and Nanomi BV, recently acquired by the multinational Lupin.
CAREMI’s main objective is the clinical evaluation of CMC cells. The initial studies of the scaling-up phase of the clinial trial were conducted at the Hospital Gregorio Marañón (Madrid) under the direction of Prof. Francisco Fernández-Avilés, and at the University Hospital of Leuven (UZ Leuven, Belgium), coordinated by Prof. Stefan Janssens. As announced last Friday, CAREMI completed the first clinical trial phase of six patients, with no adverse effects. The final phase has now begun, and will include 49 new patients, for which four additional Spanish hospitals will join the Hospital Universitario Vall d'Hebron in the consortium. In addition to being the main promoter of CAREMI, Coretherapix is the sponsor of the clinical trial and is responsible for product development; it is also developing a new cell production platform in collaboration with iBET, which will allow the boost that will be needed for a more advanced clinical stage.