PH-HFpEF Patients Show Initial Response to Levosimendan in HELP Trial, Data Show

Preliminary data from the Phase 2 HELP study testing levosimendan as a potential treatment for pulmonary hypertension (PH) patients with heart failure and preserved ejection fraction (PH-HFpEF) showed that 86% of those analyzed responded to the therapy, with less pressure evident on heart’s left atrium.

The ongoing trial’s predefined response criterion — the response that needs to be seen before patients are randomized to treatment or placebo — is a reduction in pulmonary capillary wedge pressure (PCWP), a measure of the pressure on the left atrium.

Levosimendan belongs to a class of compounds known as calcium sensitizers. It works through a unique mechanism of action that helps to improve heart muscle contraction without increasing the need for oxygen.

The therapy, developed by Tenax Therapeutics, is being tested in the HELP trial (NCT03541603) in people with PH-HFpEF patients. (Of note, ejection fraction refers to how much blood the heart’s left ventricle pumps out with each contraction.)

So far, 24 patients are enrolled, up from 15 at the end of October; the study’s recruitment goal is 36 adults with confirmed PH-HFpEF.

Patients are being randomly assigned to six weekly infusions of levosimendan or a similar dose of placebo. This short-term study will evaluate the impact of the investigational treatment on patients’ exercise capacity.

All who complete this six-week, double-blind trial phase can enroll in a two-year, open-label extension study (NCT03624010).

Specifically, HELP’s predefined response criterion stipulates that, by 24 hours after one infusion, each patient’s PCWP must have decreased by 4 mmHg or more during supine (laying down) exercise.

In total, 24 people (out of 28 analyzed, about 86%) to date achieved this response, showing a statistically significant improvement in PCWP compared to measures taken prior to the treatment. The average reduction was 7.6 mmHg, Tenax reported in a news release.

Twenty-two of the 24 also had a significant average reduction in pulmonary arterial pressure of 4.9 mmHg, and in right atrial pressure of 5.2 mmHg. Their cardiac output — the amount of blood pumped by the heart — increased on average by 0.8 liters/min. All these outcomes were statistically significant.

No serious adverse events due to levosimendan’s initial use were reported, and no one has withdrawn from the study.

“We are pleased that enrollment rates have been consistently increasing, and initial responses continue to exceed our expectations,” Tony DiTonno, CEO of Tenax Therapeutics, said in the release.

The trial is now running at 16 clinical sites across the U.S., and Tenax expects to finish enrolling patients by April. For more information on trial locations and contacts, please visit the webpage here.

“We anticipate completing this trial in the months to come, and quickly moving forward to the next phase of our development efforts to make levosimendan available to those patients suffering from this debilitating disease,” DiTonno said.