Windtree Therapeutics has dosed the first patient in its Phase 2 study of istaroxime in patients experiencing early cardiogenic shock. Early cardiogenic shock is one of two developmental programs for istaroxime. The second is acute heart failure, which is supported by positive phase 2a and phase 2b trial results and a FDA Fast Track designation.
"Cardiogenic shock is a life-threatening state of lack of heart function and blood flow to vital organs that is associated with high risk of mortality, despite intensive montoring and current treatments," said Craig Fraser, Chief Executive Officer of Windtree. "We believe istaroxime's dual mechanism of action, improving both systolic contraction of the heart as well as diastolic function, along with positive effects on blood pressure, could be a key approach in effectively bringing severe acute heart failure patients out of this critical condition. Additionally, because of the unmet need in cardiogenic shock and the regulatory precedent in this area, we believe positive data could lead to an opportunity for breakthrough therapy designation, which may provide for an expedited development program."
The istaroxime Phase 2 study is an international randomized double blind placebo controlled study to assess the effect of istaroxime in patients with early cardiogenic shock due to heart failure. This study will include 60 patients (30 assigned to istaroxime and 30 assigned to placebo) receiving study drug infusion over 24 hours. The primary endpoint is the change in systolic blood pressure over six hours after initiating the infusion. Secondary endpoints will include characterization of blood pressure changes over 24 hours, the number of patients requiring rescue therapy (vasopressors, inotropes or mechanical devices), assessment of renal function and measures associated with safety and tolerability. Regulatory precedent exists for an approval in shock settings based upon improvements in blood pressure with an acceptable safety profile. Based on positive data from the acute heart failure studies, the Company is starting its program in the patients experiencing early cardiogenic shock due to severe heart failure and, if the data is positive, the Company would plan to expand the study population in future development.
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"Patients in early cardiogenic shock due to heart failure have decreased cardiac output with very low blood pressure resulting in a critical reduction of blood flow. Data from the istaroxime Phase 2 program in acute heart failure showed that istaroxime significantly improved cardiac function and increased systolic blood pressure. Importantly, istaroxime produced these changes without an increase in clinically significant arrythmias or increases in cardiac troponins. Istaroxime may represent a novel treatment strategy for acute treatment of early cardiogenic shock due to progression of heart failure," Steve Simonson, M.D., Chief Medical Officer of Windtree, said.
Istaroxime is a first-in-class dual mechanism therapy designed to improve both systolic diastolic cardiac function. Istaroxime is a positive inotropic agent that increases myocardial contractility through inhibition of Na+/K+-ATPase with a complimentary mechanism that facilitates myocardial relaxation through activation of the SERCA2a calcium pump on the sarcoplasmic reticulum enhancing calcium reuptake from the cytoplasm. Data from multiple Phase 2 studies in patients with acute heart failure (AHF) demonstrate that istaroxime infused intravenously significantly improves cardiac function and blood pressure without causing heart rate increases or rhythm disturbances.