Tenax expands development of PH treatment TNX-103
Phase 3 trials to support therapy's advancement
Tenax Therapeutics said it will extend its Phase 3 clinical development of an oral form of levosimendan for pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).
The company last year received $100 million in funding to help it complete an ongoing Phase 3 LEVEL trial (NCT05983250) testing TNX-103.
Tenax said it will now extend recruitment to at least 230 participants, increasing the trial’s statistical power. The study is taking place at several sites in North America. Full enrollment is expected by the end of 2025, and top-line data by mid-2026.
The company also said it received clearance from the U.S. Food and Drug Administration to initiate a second Phase 3 trial, LEVEL-2, which plans to start enrolling patients this year.
“We expect these two registrational studies will satisfy the requirements, including the safety data expectations, to file in the U.S. and other geographies,” Chris Giordano, Tenax’s president and CEO, said in a company press release. “We are funded well beyond our projected date for the release of topline LEVEL data, positioning us to advance the development of TNX-103 and improve the quality of life for patients living with PH-HFpEF.”
PH treatment relaxes blood vessels
In PH-HFpEF, although the heart beats normally and pumps a normal amount of blood, the heart muscle is abnormally stiff and fails to relax properly. As a result, the heart’s left ventricle, the main pumping chamber, cannot keep up with the blood returning from the lungs, leading to PH, or high blood pressure in the pulmonary arteries.
Levosimendan is thought to work by relaxing blood vessels by acting on a potassium channel, reducing the amount of blood that puts pressure on blood vessels’ walls. It may also help protect the heart muscle while promoting heart contraction.
The LEVEL trial is testing TNX-103’s efficacy at increasing exercise capacity in adults with PH-HFpEF, ages 18-85, as assessed with the six-minute walk distance test, or how long a person can walk in six minutes on a hard, flat surface. Participants are assigned to receive the treatment (2 mg/day for weeks one to four and then at 3 mg/day) or a placebo, for 12 weeks (about three months).
After trial completion, patients will have the option to enroll in a 92-week open-label extension (OLE).
As of late February, TNX-103 treatment was well tolerated in participants with PH-HFpEF, with more than 95% remaining on therapy and electing to enter the OLE study, Tenax said. A similar percentage has continued in the extension study.
“In addition to high rates of study and therapy continuation, the adherence … has been high, and no new safety signals have been detected,” said Stuart Rich, MD, Tenax’s chief medical officer. “About half the patients in the OLE have been on study for over 6 months, a few of them for more than a year, with very reassuring participation levels observed during the OLE.”
The LEVEL-2 study will evaluate TNX-103 in people with PH-HFpEF in several countries. Participants will receive the treatment at a dose of 2 mg/day for the first four weeks and 3 mg/day from week five onward, or a placebo. The trial’s main goal is also to assess changes in exercise capacity at about six months.
The company intends to enroll a larger number of patients in this trial than in the LEVEL study, and to evaluate patients for up to one year. This, according to Tenax, would provide robust safety data to U.S. and European regulatory authorities.
“TNX-103 has the potential to meaningfully improve the quality of life of patients with PH-HFpEF, an underdiagnosed disease with significant unmet needs and no currently approved treatment options,” Rich said. “I remain very hopeful that with positive Phase 3 results, these patients will finally have an approved treatment available.”
In the Phase 2 HELP trial (NCT03541603), weekly infusions of TNX-101, an into-the-vein formulation of levosimendan, in adults with PH-HFpEF reduced heart pressure and improved exercise capacity after six weeks, compared with a placebo.
Switching from infusions to oral levosimendan was well tolerated, and further improved patients’ exercise capacity, according to OLE data.
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