CHAPEL HILL – Tenax Therapeutics plans to narrow enrollment in its next Phase 3 trial after TNX-103 missed the primary and key secondary endpoints in the LEVEL study, while subgroup analyses showed stronger results among patients with lower baseline walking distance.
The Chapel Hill development-stage drug company presented additional analyses Aug. 29 at the European Society of Cardiology Congress in Munich. LEVEL tested oral levosimendan in 241 patients with pulmonary hypertension due to heart failure with preserved ejection fraction at 41 sites in the United States and Canada.
In the overall trial population, the least-squares mean difference in six-minute walking distance at 12 weeks was 3.5 meters between TNX-103 and placebo, with a p-value of 0.63. The primary endpoint was not met. The difference in the Kansas City Cardiomyopathy Questionnaire total symptom score, the key secondary endpoint, was 0.1 points. Tenax disclosed those overall results Aug. 10.
The Aug. 29 presentation highlighted a prespecified subgroup of 119 patients whose baseline six-minute walking distance was below the trial median of 333 meters. The placebo-adjusted difference was 26.3 meters, with a nominal p-value of 0.0112.
In that subgroup, Tenax reported a 47% reduction in the cardiac-stress biomarker NT-proBNP compared with placebo and a 4.9 mmHg reduction in right ventricular systolic pressure. The company labeled both subgroup analyses post hoc. The nominal p-values were not adjusted for multiple comparisons, and the analyses do not establish efficacy.
Tenax reported Aug. 10 that adverse events occurred in 86.7% of patients receiving TNX-103 and 71.9% of patients receiving placebo. Serious adverse events were reported in 10.8% and 10.7% of the groups, respectively.
The company said it intends to enrich the patient population in the ongoing LEVEL-2 trial based on the LEVEL findings. TNX-103 remains an investigational treatment. Tenax Therapeutics’ common stock trades on Nasdaq under the symbol TENX.