Phase 3 trial of oral levosimendan in PH-HFpEF likely to open soon

LEVEL is one of two studies aiming for a first treatment for this PH type

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Tenax Therapeutics is planning to soon launch a Phase 3 clinical trial of TNX-103, an oral formulation of levosimendan, in people with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).

The company announced it received clearance from the U.S. Food and Drug Administration (FDA) to conduct two Phase 3 studies testing TNX-103 in people with PH-HFpEF.

The first trial, called LEVEL (NCT05983250), is expected to open before the year’s end, with plans to enroll about 152 adults with PH-HFpEF, ages 18 to 85. The study will be open to patients who are able to walk at least 100 meters (about 330 feet), but not more than 450 meters (nearly 1,480 feet), in six minutes, among other criteria.

“We could not be more pleased with the results of our collaborative, productive discussions with the FDA, which provide a clear path to starting LEVEL, including mutual alignment with respect to the primary efficacy endpoint and expected patient enrollment,” Chris Giordano, president and CEO of Tenax, said in a company press release.

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Pivotal oral levosimendan studies to enroll 300 or more PH-HFpEF patients

The newly cleared Phase 3 trials are expected to collect data on the use of TNX-103 for six months in at least 300 PH-HFpEF patients, with at least 100 patients treated for one year, in line with FDA requests.

In both studies, the main goal will be to test the impact of treatment on the distance that patients can walk in six minutes, which is a common measure of exercise ability in people able to walk.

LEVEL will randomly assign patients to TNX-103 or a placebo for 12 weeks (about three months). The study drug will be given at a dose of 2 mg/day for the first four weeks, and 3 mg/day for the rest of the trial. All participants will undergo a screening period of up to 30 days before starting treatment, and during the study they will be required to return to the clinical site for evaluation about once each month.

After the trial’s placebo-controlled phase, patients can enter an open-label extension where all will be treated with the therapy for 92 weeks (about two years).

The FDA is not requiring Tenax to conduct a long-term study to monitor heart health outcomes, which Giordano said “should significantly reduce our costs and time to registration for TNX-103.”

PH-HFpEF is characterized by high blood pressure in the lungs and a normal heartbeat, but the heart is too stiff to adequately get blood throughout the body. No approved treatments are available for this type of PH.

“With no approved therapies currently available in the U.S., physicians, patients and regulators increasingly recognize the significant unmet need of patients who suffer from PH-HFpEF,” Giordano said.

Levosimendan, the active agent in TNX-103, is thought to work on the body through multiple mechanisms, including activating proteins called potassium adenosine triphosphate (K+ ATP) channels.

Tenax also is developing a formulation of this drug given by infusion into the bloodstream called TNX-101, as well as one given by injection under the skin called TNX-102. All three formulations have earned U.S. patent protection for PH-HFpEF.

Smaller Phase 2 trial supported treatment’s efficacy, safety

“I am pleased to be leading this important new trial investigating TNX-103, which is designed to help advance our understanding of how K+ATP activation may provide a new approach for reducing the high central and venous blood pressures frequently associated with PH-HFpEF,” said Sanjiv Shah, MD, a professor at Northwestern University and chair of the steering committee for the LEVEL study.

An earlier Phase 2 trial called HELP (NCT03541603) suggested that treatment with the infused formulation improved exercise capacity for people with PH-HFpEF, and long-term study data indicated that switching to oral levosimendan was well tolerated overall.

“Based on its unique properties as a K+ ATP channel activator, coupled with the proof-of-concept data from the Phase 2 HELP study, TNX-103 has mechanistic potential to address the underlying pathophysiology [processes] of PH-HFpEF,” said Stuart Rich, MD, Tenax’s chief medical officer.

“We expect oral levosimendan will provide consistent drug concentration levels, supporting improved efficacy, as observed in patients who transitioned from weekly IV [into the vein infusion] to oral therapy following the HELP study,” Rich added.

All clinical sites that took part in the HELP study have been invited to participate in LEVEL, and 90% of them have agreed to be part of the Phase 3 trial, according to Tenax.

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