Windtree Reports Positive Phase 2b Results: Istaroxime Improves Cardiac Function and BP in Early Cardiogenic Shock

Windtree Therapeutics, Inc. recently reported positive topline results from its Phase 2b SEISMiC Extension Study of istaroxime in heart failure patients experiencing early cardiogenic shock. Cardiogenic shock occurs when the heart fails to pump sufficient blood, resulting in low blood pressure and inadequate blood flow to vital organs, leading to high morbidity and mortality rates.

Istaroxime is a novel investigational therapy aimed at improving heart function by enhancing both systolic contraction and diastolic relaxation. Additionally, it helps increase blood pressure and maintains renal function with a generally favorable safety profile. The drug has already shown promising results in four Phase 2 trials involving patients with acute heart failure and early cardiogenic shock.

The Phase 2b SEISMiC Part B Extension Study included 30 subjects from the United States, Europe, and Latin America. The focus of the study was to evaluate istaroxime’s ability to correct low blood pressure and improve cardiac function over a monitoring period of 96 hours, with a final follow-up visit at 30 days. The study built upon previous positive findings from the Phase 2b SEISMiC Part A study and included patients with persistent hypotension due to acute heart failure. Two different dose regimens of istaroxime were tested against a placebo: one with a decreasing dose over time and another with a constant dose.

The primary endpoint for this study was to measure systolic blood pressure (SBP) over six hours. The combined data from Part A and Part B showed that istaroxime significantly improved SBP compared to the placebo (62.0±7 vs 36.4±7 mmHg*hr, p = 0.0070). Despite the smaller sample size in Part B, significant improvements were also observed (78.4±12 vs. 39.6±14 mmHg*hr, p=0.0429). The study also demonstrated significant improvements in SBP at 24, 48, and 60 hours.

Additionally, the study reported improvements in other cardiovascular parameters. Cardiac output increased by approximately 15% during the infusion period in the istaroxime group. Importantly, there was no significant increase in heart rate, which often leads to increased cardiac oxygen demand and workload. In fact, significant reductions in heart rate were observed at 12 and 24 hours.

Pulmonary capillary wedge pressure (PCWP), which was elevated in the study subjects, was significantly reduced by istaroxime within six hours, and this effect persisted through 60 hours. PCWP is a measure of cardiac filling pressure, and high levels contribute to worsening heart failure and pulmonary edema.

Mixed venous oxygen saturation (SVO2), an indicator of organ perfusion, improved significantly within 12 hours and remained elevated through 48 hours compared to placebo. This suggests that cardiac output was sufficient to meet tissue oxygen needs.

Renal function, as measured by estimated glomerular filtration rate (eGFR), showed improvement in the istaroxime group compared to the placebo, reaching statistical significance at 48 hours.

Clinical signs of congestion and heart failure improved in both groups. The New York Heart Association (NYHA) heart failure classification significantly decreased in the istaroxime group at 24, 48, and 72 hours.

The safety profile of istaroxime in Part B was favorable, with treatment-emergent adverse events reported more frequently in the istaroxime group but primarily due to manageable side effects like nausea and headache. Serious adverse events were infrequent and similar between the istaroxime and placebo groups. Importantly, istaroxime did not increase clinically significant arrhythmias.

Dr. Alexandre Mebazaa, a heart failure expert, emphasized that istaroxime has a unique profile; it may be the only drug candidate that improves blood pressure, cardiac output, and renal function without increasing heart rate or risk for cardiac arrhythmias. These are highly desirable attributes for treating cardiogenic shock and acute heart failure.

Craig Fraser, CEO and Chairman of Windtree Therapeutics, expressed satisfaction with the study results and highlighted the consistent positive outcomes observed across four Phase 2 studies involving over 300 patients. He looks forward to advancing the development of istaroxime as a potentially important therapy for critical heart conditions.

Windtree Therapeutics is focused on developing innovative therapies for critical conditions and diseases, with its portfolio including istaroxime and other promising candidates.