Omecamtiv mecarbil is a medication that represents a new class of drugs designed to address certain heart conditions. It functions as a cardiac myosin activator, working to improve the heart’s ability to pump blood. This drug is currently being studied for its potential to help individuals with specific types of heart failure.
Understanding How It Works
Omecamtiv mecarbil directly targets the fundamental machinery responsible for heart muscle contraction. Heart muscle cells, known as cardiac myocytes, contract using two key protein filaments: actin and myosin. Chemical energy (ATP) is converted into mechanical energy, allowing myosin to bind strongly to actin and generate a “power stroke” that shortens muscle fibers, leading to contraction. This medication activates cardiac myosin, influencing the interaction between these filaments.
It increases the rate at which phosphate is released from myosin, accelerating a rate-determining step in the cross-bridge cycle, transitioning the actin-myosin complex from a weakly bound to a strongly bound state. Omecamtiv mecarbil also prolongs the time myosin stays bound to actin. This combined action of increased and prolonged cross-bridge formation extends the duration of myocardial contraction, enhancing the heart’s pumping function. Unlike some other heart medications, omecamtiv mecarbil improves systolic function without increasing intracellular calcium levels or myocardial oxygen consumption, which can be a concern with other inotropic therapies.
Its Role in Heart Failure Treatment
Omecamtiv mecarbil is being explored as a treatment for chronic heart failure with reduced ejection fraction (HFrEF). HFrEF is a condition where the heart’s main pumping chamber, the left ventricle, is weakened and cannot pump enough blood to meet the body’s needs. This leads to symptoms such as shortness of breath and fatigue. The goal of treating HFrEF is to improve the heart’s pumping ability, alleviate symptoms, and reduce hospitalizations and cardiovascular-related deaths.
The GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in Heart Failure) trial investigated omecamtiv mecarbil in patients with HFrEF. This large-scale study included over 8,000 patients with symptomatic HFrEF, a left ventricular ejection fraction of 35% or less, and elevated natriuretic peptides; many had been recently hospitalized for heart failure. The primary outcome, a composite of cardiovascular death or a first heart failure event (such as hospitalization or urgent visits), occurred in a smaller percentage of patients receiving omecamtiv mecarbil compared to those on placebo. Specifically, this outcome was observed in 37.0% of the omecamtiv mecarbil group versus 39.1% in the placebo group over a median follow-up of about 22 months. The benefit appeared more pronounced in patients with lower baseline systolic blood pressure and those with more severely reduced ejection fraction.
Important Patient Information
Patients should discuss potential effects of omecamtiv mecarbil with their healthcare provider. The medication is well-tolerated, with studies showing it is not associated with an increased incidence of death, hypotension, or serious adverse events compared to placebo.
A small, typically asymptomatic increase in cardiac troponin I levels has been observed in patients taking omecamtiv mecarbil. While elevated troponin can sometimes indicate heart muscle damage, in this context, the increase has not been linked to clinical signs of ischemia or an increased risk of cardiac events like arrhythmias. This elevation may be a biomarker response to the drug’s mechanism of action rather than an indication of adverse effects. Omecamtiv mecarbil may also lead to a slight decrease in heart rate.
Patients should adhere to their physician’s dosage instructions and report any new or worsening symptoms. A healthcare professional will determine its use based on individual patient characteristics and treatment plans.
Current Status and Availability
Omecamtiv mecarbil is an investigational drug. It has not yet received approval from regulatory agencies, such as the U.S. Food and Drug Administration (FDA). The FDA previously declined to approve omecamtiv mecarbil, citing a lack of sufficient evidence regarding its efficacy.
In December 2022, an FDA advisory committee voted against recommending its approval, with the FDA issuing a complete response letter in February 2023. The developer has indicated no current plans to conduct an additional clinical trial for the drug. Therefore, omecamtiv mecarbil is not currently available as a commercial treatment option for heart failure.