MORRISVILLE, N.C.– Tenax Therapeutics, Inc. (Nasdaq: TENX), a specialty pharmaceutical company focused on identifying and developing therapeutics that address cardiopulmonary diseases with a high unmet medical need, today announced a new publication that identifies a novel mechanism of action behind the improved cardiovascular hemodynamics and exercise tolerance that was reported in the recent Phase 2 HELP Study (Burkhoff et al., JACC Heart Failure 2021; 9:360-70). The HELP Study evaluated levosimendan in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF). The new publication, “Changes in Stressed Blood Volume with Levosimendan in Pulmonary Hypertension from Heart Failure with Preserved Ejection Fraction: Insights Regarding Mechanism of Action” appears in the Journal of Cardiac Failure. The article is available online as an “Article In Press”. https://www.onlinejcf.com/article/S1071-9164(21)00215-3/fulltext
The authors conducted an in-depth analysis of data from the HELP Study to elucidate the underlying mechanism behind the improved hemodynamic and exercise capacity effects seen in levosimendan-treated patients. Their analysis found that the reductions in pulmonary wedge pressure (PCWP) and central venous pressure (CVP) were independent of any inotropic effect of the drug. Instead, the authors conclude that the reduction in PCWP and CVP shown in the HELP Study was attributable to levosimendan’s ability to lower stressed blood volume (SBV) through its effect on K+ATP channel activation. The splanchnic circulation is composed of the blood that supplies all of the abdominal viscera, and serves as a reservoir to increase or decrease venous return (referred to as stressed blood volume) to the heart as dictated by physiologic conditions. It has been validated that dilating the splanchnic circulation will lower SBV and hence CVP and PCWP in PH-HFpEF (Fudim et al., JACC Heart Failure 2021; 9:293-300). As a result, patients have less shortness of breath and improved exercise tolerance.
“Recently, it has been shown that the splanchnic, or abdominal, circulation is responsible for maintaining normal venous pressure in the systemic and pulmonary vasculature via stressed blood volume levels,” said Stuart Rich, MD, Chief Medical Officer at Tenax Therapeutics stated. “This is an old concept with new relevance, as elevated venous pressures underlie the systemic and pulmonary vascular congestion in PH-HFpEF. Levosimendan is now the first drug ever to demonstrate dilatation of the splanchnic blood vessels which effectively lowers the CVP and PCWP, at rest and during exercise. As a result, it now is the only medication shown to improve exercise capacity in PH-HFpEF as well.”
Chris Giordano, CEO of Tenax Therapeutics, stated, “This publication shares new, and very important mechanistic knowledge about the effects of levosimendan in PH-HFpEF patients. Levosimendan has been acknowledged for years to be a pleiotropic drug with vasodilatory properties. This explanation of its impact on splanchnic venous capacity, in the light of the HELP primary analysis that showed levosimendan improves significantly patients’ 6-minute walk distance, provides further evidence that levosimendan is a novel therapy with the potential to provide important benefits to PH-HFpEF patients. There are currently no approved therapies for these patients.”
