Oral Formulations in Pipeline
Although the lead program at Cardioxyl is aimed at acute decompensated heart failure, nitroxyl-based drugs could also benefit patients with chronic congestive heart failure or other cardiovascular disorders. As an intravenous drug, CXL-1020 could prove ideal for treating hospitalized patients suffering from acute decompensated heart failure.
An oral drug, however, is needed to address the larger population of patients with chronic congestive heart failure and other disorders. Oral formulations of nitroxyl-based drugs for other chronic cardiovascular disorders are in preclinical testing.
Just how CXL-1020 works has not been fully defined, but researchers have shown that heart contractility and relaxation are related to calcium ion channels in cardiomyocytes, which need calcium to contract. Nitroxyl interacts with the ryanodine receptor and SERCa2a pump, both of which are involved in calcium cycling.
This calcium cycling is enhanced by nitroxyl without dramatically affecting the overall calcium load or the influx of calcium from the extracellular space, leading to more effective myocardial contraction and relaxation, Dr. Kroeger notes.
Nitroxyl also enhances calcium sensitivity of myofilaments, thereby increasing the amount of force generated. How CXL-1020 improves peripheral vascular dilation is less clear, but likely operates through different mechanisms since peripheral smooth muscle cells lack calcium channels.