Tenax's Oral Levosimendan Misses Primary Goal in Phase 3 LEVEL Heart Failure Trial

Tenax Therapeutics said on August 10 that its Phase 3 LEVEL trial of TNX-103, an oral form of levosimendan, did not meet its primary endpoint of improving six-minute walk distance versus placebo in patients with pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF). The trial also missed its key secondary endpoint, a symptom score on the Kansas City Cardiomyopathy Questionnaire, according to the company's announcement, distributed by GlobeNewswire, read via Finviz.

The results are company-reported topline data and have not yet been presented or published in full. Shares in the company lost more than 85% of their value on the morning of the announcement, pharmaphorum reported.

The LEVEL results

LEVEL was a double-blind, randomized, placebo-controlled registrational trial at 41 sites in the United States and Canada. It randomized 241 patients to TNX-103 at 1 mg twice daily, increased to 1 mg three times daily from week 5 as tolerated, or to placebo.

At week 12, walk distance rose by a least-squares mean of 14.0 meters on TNX-103 and 10.4 meters on placebo, a difference of 3.5 meters (p=0.63), the company said. On the symptom score, the difference between arms was 0.1 points.

Tenax highlighted several prespecified analyses. In the 119 patients whose baseline walk distance was below the trial median of 333 meters, the placebo-adjusted improvement was 26.3 meters (nominal p=0.0112). Across the whole trial, levels of NT-proBNP, a marker of cardiac wall stress, fell 49% compared with placebo, and right ventricular systolic pressure measured by echocardiography fell 3.5 mmHg (nominal p=0.0045). Those biomarker measures were exploratory endpoints, and the subgroup and biomarker p-values are nominal.

"Having reviewed the available trial results, I am encouraged we have a clear path forward," said Stuart Rich, Tenax's chief medical officer, in the release. He said the trial's entry criteria "enrolled a broad population, including too many patients with less severe disease."

Safety

The company said TNX-103 was generally well tolerated with no new safety signals. Adverse events were reported in 86.7% of patients on TNX-103 and 71.9% on placebo, and treatment-related adverse events in 38.3% and 17.4%. Serious adverse events occurred in 10.8% and 10.7%.

What comes next

Tenax said it intends to request a Type C meeting with the FDA to present the full dataset and discuss enriching the study population, and to seek scientific advice from the European Medicines Agency in parallel. The company said the FDA had previously agreed that a single Phase 3 trial with a p-value of 0.01 would be sufficient for a New Drug Application in PH-HFpEF.

Full LEVEL results are scheduled for a late-breaking session at the European Society of Cardiology Congress 2026 in Munich, August 28-31. A second Phase 3 trial, LEVEL-2, is under way. Intravenous levosimendan is authorized in 60 countries for acutely decompensated heart failure but is not available in the United States or Canada, according to Tenax.