Seismic Pharmaceuticals Begins Phase 3 Trial of Istaroxime in Cardiogenic Shock

Seismic Pharmaceuticals has enrolled the first patient in its global Phase 3 clinical trial evaluating istaroxime in patients with heart-failure-related cardiogenic shock.

The study, called RESCUE HF-CS, will evaluate whether istaroxime can improve heart function and help stabilize patients experiencing this life-threatening condition.

The company plans to enroll approximately 600 patients at clinical sites across the United States, Europe, China, and South America.

According to Seismic Pharmaceuticals, the trial is designed to support the development of what could become the first approved drug specifically for cardiogenic shock.

What Is Cardiogenic Shock?

Cardiogenic shock is a medical emergency that happens when the heart suddenly becomes too weak to pump enough blood around the body.

When the heart cannot pump properly, vital organs such as the brain, kidneys, and liver may not receive enough blood and oxygen.

The condition can develop as a complication of acute heart failure or other serious heart problems.

Even with improvements in emergency and intensive care treatment, cardiogenic shock remains associated with serious complications and a high risk of death.

There are currently no medications specifically approved by the US FDA to treat cardiogenic shock.

Why New Treatment Options Are Needed

Doctors currently have limited options when treating patients with cardiogenic shock.

Some medicines may be used off-label to help the heart pump more strongly. However, these treatments can have limitations, including effects on heart rate and the heart's demand for oxygen.

This creates a need for treatments that can improve the heart's pumping ability while also maintaining better overall cardiac stability.

Seismic Pharmaceuticals is developing istaroxime with this problem in mind.

What Is Istaroxime?

Istaroxime is a novel, first-in-class calcitrope being developed to improve heart function in patients with cardiogenic shock.

A calcitrope is a drug designed to improve the performance of the heart.

Istaroxime has a dual mechanism of action. In simple terms, it is designed to help the heart in two different ways.

The first action improves systolic contraction, which is the heart's ability to squeeze and pump blood out.

The second action improves diastolic relaxation, which is the heart's ability to relax and fill with blood between contractions.

This combination is intended to improve both sides of the heart's pumping cycle.

Istaroxime Uses Two Biological Mechanisms

Istaroxime works as a Na/K ATPase inhibitor and a SERCA2a activator.

The Na/K ATPase mechanism is intended to improve cardiac contractility. This can help increase blood pressure and cardiac output.

The SERCA2a activation mechanism is designed to improve how the heart muscle relaxes and handles calcium during each heartbeat.

By acting through both mechanisms, istaroxime is designed to improve cardiac performance while also supporting diastolic function.

Potential Difference From Conventional Inotropic Treatments

Traditional inotropic medicines are often used to increase the strength of heart contractions.

However, increasing the heart's activity can also increase the amount of oxygen the heart muscle needs.

Seismic says istaroxime has a different profile.

According to the company, istaroxime does not increase myocardial oxygen demand. The treatment has also been associated with reductions in heart rate and arrhythmias in Phase 2 studies.

These characteristics are important in cardiogenic shock because the heart is already under significant stress.

Phase 2 Studies Supported Further Development

The Phase 3 RESCUE HF-CS trial follows four previously completed Phase 2 studies of istaroxime.

Seismic Pharmaceuticals says these earlier studies generated clinical results that supported moving the drug into Phase 3 development.

The Phase 2 program provided information about the drug's effects on cardiac function and hemodynamics, which refers to how blood moves through the heart and blood vessels.

Istaroxime was also associated with reductions in heart rate in Phase 2 studies.

In a subset of patients who were monitored using continuous 72-hour electrocardiogram testing, the company reported a significant reduction in measures of ventricular arrhythmias.

These earlier findings will now be examined in a much larger patient population through the Phase 3 program.

RESCUE HF-CS Will Enroll Around 600 Patients

The Phase 3 RESCUE HF-CS trial is expected to enroll approximately 600 patients with cardiogenic shock.

The study will be conducted internationally, with participating clinical sites planned across four major regions.

These include the United States, Europe, China, and South America.

Running the study across multiple countries will allow researchers to evaluate istaroxime in a broad patient population and collect clinical data from different healthcare systems.

More information about the study's design, eligibility requirements, and participating sites will be made available through ClinicalTrials.gov and other applicable clinical-trial registries.

Dr Mandeep Mehra to Lead the Study

Dr. Mandeep R. Mehra, MBBS, MSc, FRCP, is the principal investigator of the study.

He is The William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Mass General Brigham Heart & Vascular Institute and a Professor of Medicine at Harvard Medical School.

Dr. Mehra said cardiogenic shock remains one of the most serious conditions treated in cardiovascular medicine, while there is still no approved pharmacological treatment specifically developed for the condition.

He said the RESCUE HF-CS trial will help determine whether istaroxime's ability to improve cardiac performance and support diastolic relaxation can provide a meaningful treatment option for critically ill patients.

Seismic Pharmaceuticals Focuses on Heart Failure

Seismic Pharmaceuticals is a biotechnology company focused on developing new treatments for heart failure.

The company combines expertise in heart failure drug development with a pipeline of therapies designed to address different aspects of cardiac disease.

Its founding portfolio includes three drug candidates: Seismic 101, Seismic 102, and Seismic 103.

Seismic Has Three Additional Drug Candidates

Seismic 101 is a dual-mechanism Na/K ATPase inhibitor and SERCA2a activator being developed for acute and advanced heart failure.

Seismic 102 is a pure SERCA2a activator being developed for acute and diastolic heart failure.

Seismic 103 is a pan-SERCA activator being developed for pulmonary hypertension.

All three candidates are currently in preclinical development.

The company expects these programs to enter clinical development in spring 2027.

Momentum Research Supports the Pipeline

Seismic Pharmaceuticals is advancing its drug programs with support from Momentum Research, Inc.

Momentum Research is described by Seismic as a greenhouse company that has been involved in the development of several successful heart failure therapies.

The company's board of directors also includes individuals with experience in heart failure drug development and clinical programs.

Seismic Pharmaceuticals is headquartered in Durham, North Carolina.

What Comes Next for Istaroxime?

The immediate focus is on enrolling patients in the RESCUE HF-CS Phase 3 trial.

Researchers will evaluate istaroxime in approximately 600 patients with heart-failure-related cardiogenic shock and assess its safety and effects on cardiac function and hemodynamic stability.

The study will build on the clinical data generated in the four previous Phase 2 trials.

If the Phase 3 program successfully demonstrates the required safety and effectiveness, the results could support discussions with regulatory authorities about the potential approval of istaroxime specifically for cardiogenic shock.

Optimize Your trial insights with Clival Database.

Are you exhausted from the uncertainty of trial insights pricing? Clival Database ensures the clarity in the midst of the global scenario for clinical trials to you.

Clival Database is one of the best databases that offers an outstanding number of clinical trial data in terms of 50,000+ molecules and from primary regulatory markets as well as new entrants like Indian and Chinese markets.

With Clival, you get accurate positioning of historical sales data, patent database, company profiling, safety & efficacy, and prediction of launch of new innovative molecules helping you to align your research and driving down the cost.

To add value, we further break down our analytics for you so that improving your operational effectiveness; optimizing your clinical trials; and offering you accurate and high-quality data at lowest possible prices becomes possible.

Elevate your trial success rate with the cutting-edge insights from Clival database.

Check it out today and make more informed sourcing decisions! Learn More!