Tenax Therapeutics announced today that the FDA has approved their expanded Phase 3 development program for TNX-103 (oral levosimendan) in treating pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF). The company will increase enrollment in their ongoing LEVEL study and launch a second global Phase 3 trial, marking a significant advancement in addressing this unmet medical need.
Enhanced LEVEL Study Design and Progress
The ongoing LEVEL study will now enroll 230 patients, up from the initially planned 152, substantially increasing the trial's statistical power to over 95%. With more than 50 North American sites actively participating, Tenax expects to complete enrollment by the end of 2025, with topline data anticipated by mid-2026.
Early blinded data from the trial demonstrates encouraging safety and tolerability profiles:
- Over 95% of randomized patients maintaining therapy
- More than 95% of 12-week completers entering the open-label extension (OLE)
- Above 95% continuation rate in the OLE phase
"The adherence to the TID regimen has been high, and no new safety signals have been detected," noted Dr. Stuart Rich, Tenax Therapeutics' Chief Medical Officer. "About half the patients in the OLE have been on study for over 6 months, some exceeding a year, with very reassuring participation levels."
LEVEL-2: Expanding Global Reach
The newly approved LEVEL-2 study will commence enrollment this year across multiple countries. This second registrational trial will evaluate patients over a full year of double-blind, placebo-controlled therapy, with the primary endpoint measuring 6-minute walk distance (6MWD) at 26 weeks. The expanded trial design aims to provide robust safety data for regulatory review in both U.S. and European markets.
Clinical Trial Details
The LEVEL study protocol includes:
- Double-blind, randomized, placebo-controlled design
- 1:1 randomization ratio
- Dosing regimen: 2 mg/day (Weeks 1-4), increasing to 3 mg/day (Weeks 5-12)
- Primary outcome: Change in six-minute walk distance from baseline to Week 12
- 92-week open-label extension option
Financial and Strategic Position
Chris Giordano, President and CEO of Tenax Therapeutics, emphasized the company's strong financial position following their $100 million financing secured in August 2024. "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," stated Giordano.
Therapeutic Significance
TNX-103 represents a potential breakthrough in PH-HFpEF treatment, a condition currently lacking approved therapies. The drug's mechanism of action includes potassium ATP channel activation and calcium sensitization, affecting both heart and vascular function. Previous Phase 2 HELP study results demonstrated improved exercise capacity through effective dilation of central and pulmonary venous circulations, a crucial finding that underlies the current Phase 3 program.
