Windtree Therapeutics Announces Reduction In Arrhythmias In A New Study With Istaroxime And A Pure SERCA2a Activator

Arrhythmias are irregular heartbeats that can impact the pumping function of the heart. Patients with heart failure and cardiomyopathy are at risk for arrhythmias. Arrhythmias in these patients can be caused by their underlying cardiac disease or by drugs used to treat heart failure such as catecholamines. Arrhythmias can impair the proper filling of the heart with blood and, importantly, cardiac output to the body. Ventricular arrhythmias are particularly dangerous and can be fatal. 

Innovative drugs have the potential to treat acute heart failure and cardiogenic shock to improve cardiac function without increasing the risk for arrhythmias. Acute decompensation of heart failure is responsible for approximately 1.3 million hospital admissions in the U.S. and approximately 1.5 million in the EU. It is the number 1 cause of U.S. hospitalizations in patients >65 years of age and is the most expensive Medicare diagnosis to treat. Cardiogenic shock can be a severe presentation of heart failure characterized by low blood pressure and inadequate blood flow to vital organs. It has a mortality rate as high as 30-40% and substantial morbidity in survivors. Istaroxime is administered intravenously in the hospital where acute heart failure and cardiogenic shock patients are treated. CVie-216 is in the preclinical stage of development and has the potential for intravenous administration or oral (tablet) use in the outpatient setting in chronic heart failure. Chronic heart failure affects approximately 6 million people (nearly 2% of the adult population) in the U.S. The combined U.S., EU and Japan market has more than 18 million patients with chronic heart failure. 

Windtree New Preclinical Data

Windtree Therapeutics WINT just announced new preclinical data on the company’s lead product candidate, istaroxime, and another preclinical pipeline drug candidate, CVie-216, showing reductions in ventricular arrhythmias in a rat heart model of diabetes with restricted and restored coronary blood flow induced injury. Istaroxime and CVie-216 are each designed to act on pumps in the cardiac cells that are important in calcium handling. Istaroxime is a dual mechanism of action compound that has been shown to inhibit the sodium potassium ATPase and activates SERCA2a. CVie-216 is designed to selectively activate SERCA2a. 

Nearly 300 patients with acute decompensated heart failure were treated with istaroxime in three phase 2 studies, including a study that evaluated patients with early cardiogenic shock. In these studies, istaroxime has not been associated with an increase in clinically significant arrhythmias, raising the potential for a new therapy with substantial advantages over current rescue drug therapies used to treat acute heart failure and cardiogenic shock. Windtree is continuing to obtain data to evaluate the potential benefits of SERCA2a activation on arrhythmia risk in all ongoing clinical trials. To further explore this potential benefit associated with SERCA2a activation, Windtree conducted a study of restricted and restored coronary blood flow-induced injury in the hearts of rats with diabetes that were infused with either istaroxime, pure SERCA2a activator CVie-216 or placebo (control). The rat model generated a reproducible incidence of ventricular arrhythmias. This study demonstrated a reduction in arrhythmias in the istaroxime and CVie-216 pretreated groups compared to the control group. The company plans to publish the results and is in the process of pursuing additional intellectual property protection based on these findings.

“This new data suggests that improving SERCA2a activity has the potential to improve arrhythmia risk as well as improve overall cardiac function,” said Craig Fraser, CEO of Windtree Therapeutics. “We expect to continue to obtain additional data in our ongoing clinical trial to characterize the impact of our SERCA2a activation with istaroxime on clinically significant arrhythmias and we expect to extend these observations with additional preclinical work with the oral SERCA2a Activators.” 

Featured photo courtesy of Windtree Therapeutics.

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