Windtree Therapeutics is making strides in the clinical development of istaroxime, a novel therapy for acute heart failure (AHF) and cardiogenic shock. The company anticipates topline data from its Phase 2b SEISMiC Extension Study in early cardiogenic shock patients (SCAI Stage B) by the end of this quarter. This study builds upon positive results from the original SEISMiC trial and focuses on optimizing the dose and further characterizing the SERCA2a effects of istaroxime in up to 30 patients.
The SEISMiC Extension Study evaluates two different dosing regimens of istaroxime compared to placebo, with infusions lasting up to 60 hours. This extended duration aims to provide additional benefits compared to the previous study, which limited treatment to 24 hours. The study also collects detailed data on heart function, specifically related to the SERCA2a mechanism of action. Istaroxime's unique profile, which has not been associated with increased cardiac arrhythmias, could differentiate it from currently used inotropes and vasopressors.
Parallel Study in SCAI Stage C Cardiogenic Shock
Windtree is also advancing a parallel study in patients with more severe cardiogenic shock (SCAI Stage C). This placebo-controlled, double-blinded study will assess the effect of istaroxime when added to the current standard of care, including inotropes or vasopressors, in up to 20 patients. The primary endpoint is the assessment of systolic blood pressure (SBP) area under the curve over the first 6 hours of treatment. Secondary endpoints include SBP changes at specified timepoints, the vasopressor-inotrope score, progression to SCAI Stage D or E cardiogenic shock, time to treatment failure, arrhythmia assessments, days alive and out of the hospital through day 30, physiologic measures (e.g., cardiac index), and length of stay in the ICU and hospital. The execution of this study is contingent upon securing adequate resources.
Licensing Agreement with Lee's Pharmaceutical
In January 2024, Windtree entered into a licensing agreement with Lee’s Pharmaceutical (HK) Limited for the development and commercialization of istaroxime in Greater China, including for AHF and cardiogenic shock. The agreement also includes Windtree’s preclinical next-generation dual mechanism SERCA2a activators and rostafuroxin, a Phase 2 product candidate for hypertension associated with specific genotypes. The deal provides Windtree with potential future milestones of up to $138 million, plus low double-digit royalties, with Lee’s covering all development, manufacturing, regulatory, and commercialization costs in the licensed territory.
Istaroxime: A Novel Dual-Mechanism Therapy
Istaroxime is a first-in-class therapy designed to improve both systolic and diastolic cardiac function. It acts as a positive inotropic agent by increasing myocardial contractility through inhibition of Na+/K+-ATPase, while also facilitating myocardial relaxation by activating the SERCA2a calcium pump on the sarcoplasmic reticulum, enhancing calcium reuptake from the cytoplasm. Phase 2 data in patients with early cardiogenic shock or acute decompensated heart failure have demonstrated that intravenous istaroxime significantly improves cardiac function and blood pressure without increasing heart rate or the incidence of cardiac rhythm disturbances.
According to Craig Fraser, CEO and Chairman of Windtree Therapeutics, the company is pleased with its progress in clinical development, given the high unmet needs in the patient populations being studied. He also expressed satisfaction with the licensing partnership with Lee’s, which will help advance the program in acute heart failure.
