Windtree Therapeutics announced positive topline results from its Phase 2b SEISMiC Extension Study, evaluating istaroxime in heart failure patients experiencing early cardiogenic shock. The trial demonstrated significant improvements in systolic blood pressure (SBP) and cardiac function, suggesting istaroxime's potential as a novel treatment for this critical condition.
Key Findings from the SEISMiC Part B Extension Study
The Phase 2b study randomized 30 patients with SCAI Stage B cardiogenic shock across the United States, Europe, and Latin America. Participants received either a decreasing dose or a constant dose of istaroxime over 60 hours, compared to placebo. The primary endpoint, SBP improvement, was met with statistically significant results.
Specifically, the combined analysis of Part A and Part B showed that istaroxime significantly improved SBP AUC over six hours (62.0±7 vs 36.4±7 mmHghr, p = 0.0070). Part B alone also demonstrated significant improvement (78.4±12 vs. 39.6±14 mmHghr, p=0.0429).
Impact on Cardiac and Renal Function
Beyond blood pressure, istaroxime also showed positive effects on cardiac output, increasing it by approximately 15% during the infusion period. Importantly, heart rate either decreased or showed no statistically significant increase compared to placebo. Reductions in heart rate were statistically significant at 12 and 24 hours (p = 0.0102 and p = 0.0218, respectively).
Pulmonary capillary wedge pressure (PCWP) was significantly reduced with istaroxime treatment compared to placebo within six hours (-6.6 vs -0.9 mmHg, p = 0.0001), an effect that persisted through 60 hours. Mixed venous oxygen saturation (SVO2), a measure of organ perfusion, also improved significantly by 12 hours (p=0.0071) and remained significant through 48 hours (p=0.0001).
Renal function, as measured by estimated glomerular filtration rate (eGFR), improved in the istaroxime group compared to placebo, reaching statistical significance at 48 hours (p =0.0291).
Clinical Improvements and Safety Profile
Patients treated with istaroxime experienced improvements in clinical signs and symptoms of congestion and heart failure. The New York Heart Association (NYHA) classification of heart failure severity significantly decreased in the istaroxime group at 24 hours (p=0.020), 48 hours (p=0.035), and 72 hours (p=0.010).
Worsening heart failure, reported as a serious adverse event, occurred less frequently in the istaroxime group compared to placebo (5.3% versus 18.2%, respectively). The safety profile of istaroxime in Part B was consistent with previous trials, with no increase in clinically significant arrhythmias compared to placebo.
Expert Commentary
Alexandre Mebazaa, MD, PhD, FESC (Université Paris Cité, France), highlighted istaroxime's unique profile: "It may be the only drug candidate that has been shown to simultaneously improve blood pressure, cardiac output and renal function without increasing heart rate or risk for cardiac arrhythmias. These are all desirable attributes for a drug treating cardiogenic shock and acute heart failure."
Future Directions
Windtree Therapeutics plans to present further details from the study at a Virtual Investor Day. The company is also preparing for a late-stage Phase 3 clinical trial to further evaluate istaroxime's efficacy and safety in patients with early cardiogenic shock.
