Tenax Therapeutics (Nasdaq: TENX) has announced that its Phase 3 LEVEL clinical trial evaluating TNX-103, an oral form of levosimendan, failed to meet its primary endpoint.
The trial, which enrolled 241 patients with pulmonary hypertension associated with heart failure with preserved ejection fraction, known as PH-HFpEF, reported topline results on August 10, 2026.
Levosimendan was originally discovered and developed in the 1990s by Orion Corporation in Finland as an intravenous treatment for acutely decompensated heart failure.
Despite being approved in approximately 60 countries, the drug has never received regulatory clearance in the United States, making the LEVEL trial a critical milestone for the company.
The study did not meet its primary endpoint of change in six-minute walk distance, recording a least-squares mean difference of 3.5 meters with a p-value of 0.63, far short of statistical significance.
Patients taking TNX-103 improved their exercise capacity by 14 meters on the six-minute walking test, compared to an improvement of 10.4 meters seen in the placebo group.
The trial also failed to achieve its key secondary endpoint, which measured improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score versus placebo.
Despite the headline failures, prespecified subgroup analyses identified a substantial beneficial treatment effect in patients with greater disease burden, offering the company a potential path forward.
Clinically meaningful changes were also observed in predefined cardiac biomarker and pulmonary hemodynamic measures across the overall trial population, and TNX-103 was described as generally safe and well tolerated.
Serious adverse events and adjudicated clinical worsening events were reported as balanced across treatment arms, which Tenax cited as a positive signal for the drug’s safety profile.
Based on the LEVEL results, Tenax intends to request a Type C Meeting with the U.S. Food and Drug Administration to discuss revisions to the ongoing registrational development of levosimendan for PH-HFpEF.
The company also plans to seek parallel scientific consultation from the European Medicines Agency as it considers how to reshape its regulatory strategy across both major markets.
A key focus will be enriching future trial enrollment to target patients with greater disease burden, where the subgroup data suggested a more meaningful treatment response.
Investors and analysts will be watching closely for any changes to the ongoing LEVEL-2 trial, as well as the full LEVEL data presentation scheduled for the ESC Congress on August 29, 2026.
Tenax remains a cardiopulmonary developer without any approved products currently generating revenue, with oral levosimendan representing its primary commercial pipeline asset.
The failed pivotal trial prompted a sharp decline in the company’s share price, as investors reassessed both the likelihood and timeline of Tenax’s main commercial prospect rather than simply discounting one asset within a broader portfolio.