The first participant has been enrolled in a Phase 2 trial testing the investigational therapy levosimendan in pulmonary hypertension (PH) patients with heart failure and preserved ejection fraction (PH-HFpEF).
Ejection fraction refers to how much blood the heart’s left ventricle pumps out with each contraction. In PH-HFpEF, the cardiac muscles are too weak to pump and fill blood properly, although the heart beats normally.
Tenax Therapeutics’ levosimendan is designed to improve heart contraction by increasing the sensitivity to calcium of troponin C — a protein responsible for binding calcium to activate muscle contraction. The treatment also opens potassium channels in smooth muscle cells, which help dilate blood vessels, and in mitochondria (energy-providing cells) of cardiomyocites (heart muscle cells), resulting in a protective effect, according to the company.
The Phase 2 trial (NCT03541603), named HELP — which stands for Hemodynamic Evaluation of Levosimendan in Patients with PH-HFpEF — will include 36 adults with PH-HFpEF, at 10 to 12 major research institutions across the U.S.
The trial will assess the hemodynamic, or blood flow, benefits of levosimendan compared with placebo.
To be eligible, patients must be able to walk at least 100 meters, but not more than 400 meters in a six-minute walk test, among other criteria. Patient enrollment is ongoing; more information on contacts and locations is available here.
“Enrolling our first patient is an important milestone for the HELP trial,” Anthony DiTonno, Tenax’s CEO, said in a press release. “We have been working closely with our highly regarded principal investigators who are actively screening patients for the trial, and we expect additional centers to start enrolling patients over the coming weeks.”
According to Tenax, HELP’s design has been guided by preclinical and clinical studies, as well as by substantial clinical experience from more than 1 million patients treated with levosimendan in more than 60 countries, where the therapy is approved to treat acute heart failure.
Levosimendan is marketed in Europe as Simdax by Finland-based Orion Pharma, which originally developed the therapy. Tenax acquired the North American rights to develop and market levosimendan from Phyxius Pharma, a subsidiary of Tenax, in 2013.
Early data of levosimendan in people with PH and heart failure support its development as a potential treatment for this patient population. A Phase 3 trial (NCT02133105) showed that moderate infusion doses of levosimendan — 0.1 micrograms per kilogram of body mass per minute — improved kidney function in these patients. Kidney function is commonly impaired in patients with heart failure.
In a rat model of PH, levosimendan was shown to improve the heart’s right ventricular function, a key determinant of prognosis in PH-HFpEF patients.