Tenax Therapeutics' Phase 3 LEVEL Trial of TNX-103 Fails to Meet Primary Endpoint in PH-HFpEF
核心洞察
Tenax Therapeutics' oral levosimendan (TNX-103) failed to improve 6-minute walk distance versus placebo in the Phase 3 LEVEL trial for pulmonary hypertension due to HFpEF.
The drug also missed the key secondary endpoint of improvement in Kansas City Cardiomyopathy Questionnaire total symptom score.
A subgroup of patients with more severe disease showed a 26-metre improvement in walk distance and a 49% decrease in NT-proBNP, prompting the company to seek FDA and EMA guidance.
Tenax Therapeutics suffered a devastating setback this morning as its lead drug candidate TNX-103, an oral formulation of the calcium sensitizer levosimendan, failed to meet its primary endpoint in the Phase 3 LEVEL trial. The study evaluated the drug in patients with pulmonary hypertension due to heart failure with preserved ejection fraction (搜索) (PH-HFpEF), a condition for which no FDA-approved therapies currently exist.
The topline results showed that TNX-103 was unable to improve how far patients could walk in a 6-minute walk distance test compared with placebo. The drug also missed the key secondary endpoint of improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score, a measure of heart failure-related quality of life.
Shares of the North Carolina-based biotech lost more than 85% of their value in the wake of the announcement. Cantor analyst Olivia Brayer Saunders described the topline result as "ugly," according to a Reuters report.
Subgroup Analysis Offers Glimmer of Hope
Despite the overall failure, Tenax highlighted a potential path forward based on a subgroup analysis. Among patients who walked less than the trial median of 333 meters at baseline—indicating more severe disease—there was a 26-metre improvement in the 6-minute walk distance compared to placebo. This was accompanied by a 49% decrease in NT-proBNP, a key biomarker for heart failure severity, and what the company described as a "clinically meaningful" reduction in systolic blood pressure.
"Having reviewed the available trial results, I am encouraged we have a clear path forward," said Tenax's chief medical officer Stuart Rich. He suggested that LEVEL had enrolled "too many patients with less severe disease," which may have diluted the treatment effect.
Rich further asserted: "Taken together, these data support TNX-103's substantial cardiovascular and pulmonary biologic effects on reducing the severity of disease in patients with pulmonary hypertension due to HFpEF."
Regulatory Path and Next Steps
Tenax plans to request meetings with both the FDA and the European Medicines Agency (EMA) to discuss whether the current approach can be revised to support a regulatory filing based on the subgroup findings. Full results from the LEVEL trial are due to be presented at the European Society of Cardiology (ESC) congress in Munich, Germany, later this month.
The company is also conducting a second trial of the drug, LEVEL-2, which began enrollment in March.
Background on TNX-103
TNX-103 is an oral formulation of levosimendan, a calcium sensitizer. While intravenous levosimendan is well established as a therapy for people with advanced heart failure, it was never introduced in the United States and Canada. Tenax has been developing both IV and oral forms specifically for PH associated with HFpEF, an indication with significant unmet medical need.
The LEVEL trial outcome represents one of the most consequential binary events in biotech this year, with Tenax's entire future resting on this single drug and indication. The company has no fallback plan, making the regulatory discussions with the FDA and EMA critical to its survival.