Phase 2 Trial of Levosimendan in PH-HFpEF Patients Fully Enrolled

The Phase 2 HELP study testing levosimendan as a potential treatment for pulmonary hypertension (PH) has exceeded its target number and is fully enrolled, Tenax Therapeutics announced.

The trial (NCT03541603), testing the potential therapy in PH patients with heart failure and preserved ejection fraction (PH-HFpEF), enrolled 37 people.

Ejection fraction refers to how much blood the heart’s left ventricle pumps with each contraction. In PH-HFpEF patients, cardiac muscles are too weak to pump and fill with blood properly, although the heart beats normally.

“We are delighted that enrollment has been completed in this Phase 2 trial, and anticipate top line data to be reported during the second quarter 2020 following the completion of dosing and data analysis,” Anthony DiTonno, CEO of Tenax Therapeutics, said in a press release.

Patients in HELP are being randomized to treatment with weekly infusions of levosimendan (2.5 mg/mL dose), or to a placebo.

First, however, all were given one infusion of levosimendan prior to randomization to either group, with the requirement that they show a reduction of at least 4 mmHg in their pulmonary capillary wedge pressure (PCWP; a measure of pressure on the left side of heart) during supine (laying down) exercise 24 hours after this single treatment.

A total of 44 patients were treated, and 37 (about 84%) had the required response and are continuing in the trial. Thirty-six adults with confirmed PH-HFpEF was its initial target enrollment.

HELP’S primary goal, or endpoint, is the change from study start (baseline) in PCWP with bicycle exercise six weeks after the start of weekly levosimendan infusions (total of five treatments after randomization).

Exercise measures from the first 30 patients completing the pre-trial single treatment showed significant improvements from baseline, with an average reduction of 7.5 mmHg in PCWP.

Statistically significant improvements were also seen in pulmonary arterial pressure (mPAP; average reduction of 5.1 mmHg), right atrial pressure (average reduction, 5.0 mmHg), and cardiac output (average increase of 0.6 liters/min of blood pumped by the heart).

No therapy-related serious adverse events have been reported, the company said in its release. One patient stopped treatment before finishing the six weeks of treatment for reasons not given, while all others at this stage are continuing with, or starting, levosimendan in a two-year, open-label extension study (NCT03624010).

Levosimendan is a calcium sensitizer, initially developed for patients with heart failure. It works to improve heart muscle contraction, without increasing the demand for more oxygen.

The therapy is also designed to have a protective effect on heart muscle, and works as a vasodilator, widening blood vessels and improving blood flow and oxygenation.

“Pulmonary hypertension due to left heart disease represents a significant unmet medical need given the lack of effective therapies,” DiTonno said. “Levosimendan with its triple mechanism of action has the potential to represent a breakthrough treatment option for these patients.”