The Food and Drug Administration (FDA) has granted Fast Track designation to istaroxime (Windtree Therapeutics) for the treatment of acute heart failure (HF).
Istaroxime is a first-in-class, dual-action, luso-inotropic agent that increases myocardial contractility through inhibition of Na+/K+-ATPase. It also activates the SERCA2a calcium pump on the sarcoplasmic reticulum enhancing calcium reuptake from the cytoplasm resulting in myocardial relaxation.
The efficacy, safety and tolerability of istaroxime was evaluated in two phase 2 clinical trials in 120 hospitalized patients with worsening HF and left ventricular systolic dysfunction. The phase 2a HORIZON study evaluated the hemodynamic effects of 6-hour intravenous (IV) infusions of 3 different doses of istaroxime (0.5, 1.0, and 1.5mcg/kg/min). Results showed the study met its primary end point demonstrating a statistically significant improvement in lowering the pulmonary capillary wedge pressure (PCWP) for all doses of istaroxime (P <.05), compared with placebo; favorable effects were also observed in key secondary end points, measuring increased systolic blood pressure and decreased heart rate.
The phase 2b study investigated the safety and efficacy of 24-hour IV infusions of 2 doses of istaroxime (0.5 and 1.0mcg/kg/min), compared with placebo. The primary end point was the change from baseline in E/e’ ratio. Findings from the study showed a significant improvement in cardiac function at both doses (P <.05) with a mean E/e’ ratio of -4.55 for the 0.5mcg/kg/min group and -3.16 for the 1.0 mcg/kg/min group, compared with E/e’ ratios of -1.55 and -1.08 for placebo, respectively. Stroke volume, a key secondary end point, substantially increased in both dosing groups as well.
Regarding safety, the most common treatment-emergent adverse events included pain at infusion site associated with the use of short catheters and dose-related gastrointestinal adverse effects.
“Istaroxime is a novel, dual-action agent that impacts both the systolic and diastolic function of the heart in patients hospitalized with acute heart failure,” said Craig Fraser, President and Chief Executive Officer. “We look forward to continuing our work with the FDA and the cardiology community to advance istaroxime through clinical development and the regulatory approval process, with the goal of bringing to market a transformative therapy to treat acute heart failure patients.”
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