Chapel Hill, N.C., August 10, 2026
Tenax Therapeutics, Inc. announced topline results from the Phase 3 LEVEL clinical trial evaluating TNX-103 (oral levosimendan) in patients with pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF). The study did not achieve statistical significance on its primary endpoint of improvement in 6-minute walk distance (6MWD) compared with placebo, or on the key secondary endpoint of Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS). However, prespecified analyses identified potentially meaningful treatment effects among patients with greater disease burden, including a 26.3-meter improvement in 6MWD in patients with baseline walking distance below 333 meters. TNX-103 also produced a 49% reduction in NT-proBNP compared with placebo and a 3.5 mmHg reduction in right ventricular systolic pressure (RVSP) in the overall population.
LEVEL Trial Misses Primary Endpoint but Shows Subgroup Benefit
The LEVEL Phase 3 trial enrolled 241 patients across 41 sites in the United States and Canada and evaluated TNX-103 against placebo. The primary endpoint was change in 6MWD at Week 12. Patients receiving TNX-103 demonstrated a least-squares mean improvement of 14.0 meters, compared with 10.4 meters for placebo, resulting in a treatment difference of 3.5 meters (p=0.63). The key secondary endpoint, KCCQ-TSS, also showed no meaningful difference between treatment groups. However, a prespecified analysis of patients with baseline 6MWD below the trial median of 333 meters showed a 26.3-meter treatment difference in favor of TNX-103, with a nominal p-value of 0.0112. Patients aged 71 years and older also showed a 27.1-meter treatment difference, while patients older than 74 years demonstrated a 37.6-meter improvement compared with placebo.
TNX-103 Demonstrates Cardiovascular and Hemodynamic Effects
Beyond exercise capacity, the trial generated notable findings across cardiac biomarkers and pulmonary hemodynamics. TNX-103 produced a 49% placebo-adjusted reduction in NT-proBNP, a biomarker associated with cardiac wall stress and heart failure prognosis, with a nominal p-value below 0.0001. Treatment was also associated with a 3.5 mmHg reduction in right ventricular systolic pressure compared with placebo, with the reduction reaching 4.9 mmHg among patients with baseline 6MWD below 333 meters. Tenax said these findings support further investigation of TNX-103 in patients with greater disease burden. However, the company noted that the biomarker and hemodynamic analyses do not establish efficacy, and the reported p-values are nominal and not adjusted for multiplicity.
Advertisement
Tenax Plans FDA Meeting to Refine Phase 3 Strategy
Following the LEVEL results, Tenax Therapeutics plans to request a Type C meeting with the U.S. FDA to discuss modifications to the ongoing registrational development program for TNX-103. The company intends to explore an enrichment strategy designed to focus future development on patients with greater disease severity, based on the prespecified subgroup findings from LEVEL. TNX-103 was generally well tolerated, with serious adverse events occurring at similar rates between treatment groups. Tenax also plans to seek scientific consultation from the European Medicines Agency and will present the full LEVEL dataset at a Late-Breaking Clinical Science session during the European Society of Cardiology Congress 2026. The company continues to pursue development of oral levosimendan as a potential treatment for PH-HFpEF, a form of pulmonary hypertension for which there are currently no approved therapies.
Source: Tenax Therapeutics press release
