Each year, approximately 160,000 people in the United States suffer from ST segment-elevated myocardial infarction (STEMI), a severe type of heart attack. Approximately half of all deaths from heart attacks occur before patients reach the hospital. Although emergency medical service providers commonly give heart attack victims aspirin, better pre-hospital therapies are needed. RUC-4 was designed to be specific for alpha-IIb-beta3 and to have a unique mechanism of action that not only prevents ligand binding, but also prevents the conformational changes in the beta3 subunit induced by current alpha-IIb-beta3 antagonists that have been implicated in causing thrombocytopenia and paradoxical receptor activation. RUC-4 was also designed to have high solubility so that the likely human dose could be administered by autoinjector. The current alpha-IIb-beta3 antagonists all must be administered intravenously, a major disadvantage for pre-hospital therapy. The hypothesis is that the addition of a potent alpha-IIb-beta3 receptor antagonist to standard oral aspirin in the pre-hospital therapy of patients with ST segment-elevated myocardial infarction will not only decrease early mortality, but will also decrease the development of congestive heart failure during the next 6-12 months. This hypothesis is based on evidence showing that therapy with other alpha-IIb-beta3 antagonists (along with aspirin) soon after symptom onset can halt the progression of thrombotic myocardial ischemia to irreversible cardiac damage and decrease mortality. The BrIDGs team completed the following studies on RUC-4: - Process development - Synthesis of Good Manufacturing Practice (GMP) material - Formulation development - Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies - Investigational New Drug (IND)-directed toxicology BrIDGs completed IND-enabling activities, and the collaborators filed an IND application with the FDA. The IND was cleared in April 2019, allowing clinical trials to proceed.
