Clinical trial to evaluate the administration of ApTOLL in Acute Myocardial Infarction – ApSTEMI

In the field of cardiovascular diseases, specifically in episodes of acute myocardial infarction (AMI onwards), in recent years there have been multiple advances, especially in the treatment of reperfusion that has considerably decreased mortality, using coronary angioplasty and thrombolysis as the most effective methods. However, there are no treatments for the inflammatory process that occurs during ischemia, while the patient waits to be operated, but also for the inflammation that occurs after reperfusion. During this inflammatory process, cytokines and other proinflammatory mediators are released and it is widely described in the scientific literature that TLR4 plays a key role in both inflammatory stages, so a fast-acting antagonist in acute episodes is a treatment with great potential for this unmet medical need. The proposal of the present consortium is to study the effect of the aptamer ApTOLL, a potent antagonist of TLR4, which in animal models has shown a clear improvement in functional parameters after AMI, as well as a reduction of the damaged tissue after ischemia/reperfusion. It also has an excellent safety profile that has already been validated in a first Phase I clinical trial with healthy volunteers. Within the framework of the project, a clinical study Phase IIa will be carried out to evaluate the cardioprotective effect of ApTOLL when administered intravenously in patients admitted and diagnosed with AMI in national health service hospitals in the different autonomous communities of Spain. To carry it out, there will be the participation of the company aptaTargets owner of ApTOLL, and 4 hospitals with the «»Infarction Code»» system available 24 hours a day, seven days a week, with a cardiology hemodynamics laboratory available for the diagnosis and treatment of endovascular revascularization of STEMI (a type of myocardial infarction: AMI with ST-segment elevation in the electrocardiogram). Additionally, the study will be used to study biomarkers that contribute to the pharmacological characterization of ApTOLL and allow the project to end with a design, and preparation of the regulatory documentation necessary to start a Phase IIb/III trial. Undoubtedly, it will be a very relevant milestone to bring ApTOLL closer to the market, where a specialized company such as Destum, has valued of ApTOLL for AMI, in €1,182M once Phase II will be concluded. These values take into account the incidence of cardiovascular diseases both in the United States and in Europe, but to fully quantify the innovative treatment, we must take into account the impact that AMI has on national health systems, specifically in the case of Spain, where cardiovascular diseases (CVD) are the leading cause of death, accounting for 28.3% of all deaths. In 2017, CVD was the cause of 611,691 hospital discharges, with a hospital morbidity rate of 1,315 cases per 100,000 inhabitants. In 2018, CVD was the cause of 120,859 deaths, representing 28.3% of all deaths in Spain, above even deaths due to cancer (26.4%). According to the report prepared by AstraZeneca called Economic Cost of cardiovascular diseases from 2014 to 2020 in six European countries, France, Germany, Italy, Spain, Sweden and the United Kingdom, the total cost of CVD was calculated as 102.1 billion euros in 2014, which is approximately equivalent to gross domestic product (GDP) of a medium-sized European country, such as Hungary. This highlights the need to investigate and find effective solutions in this field.