The pivotal study failed to show a statistically significant improvement in exercise capacity or its key secondary symptom endpoint, although prespecified subgroup and biomarker findings are prompting Tenax to pursue a revised registrational strategy with the FDA.
Key Investor Takeaways
- Tenax Therapeutics (NASDAQ:TENX) said its Phase 3 LEVEL trial of TNX-103 did not meet the primary 6-minute walk distance endpoint or the key secondary KCCQ symptom endpoint.
- The overall treatment difference in 6-minute walk distance was just 3.5 meters versus placebo, with a p-value of 0.63, leaving the trial without evidence of efficacy on its primary endpoint.
- A prespecified subgroup with baseline walking distance below 333 meters showed a 26.3-meter treatment difference, while patients aged 71 and older showed a 27.1-meter difference, both reported with nominal p-values.
- TNX-103 produced a 49% placebo-adjusted reduction in NT-proBNP and a 3.5 mmHg reduction in right ventricular systolic pressure, but these exploratory analyses do not establish efficacy.
- TENX now faces a regulatory reset, with management planning a Type C FDA meeting to discuss an enriched patient population and revisions to the ongoing registrational programme.
Why TENX Stock Is in Focus
Tenax Therapeutics (NASDAQ:TENX) reported that its 241-patient Phase 3 LEVEL trial of TNX-103 in pulmonary hypertension associated with heart failure with preserved ejection fraction, or PH-HFpEF, failed its primary and key secondary endpoints.
At Week 12, the least-squares mean improvement in 6-minute walk distance was 14.0 meters for TNX-103 compared with 10.4 meters for placebo. The resulting treatment difference was 3.5 meters, with a p-value of 0.63.
The key secondary endpoint also showed little separation. KCCQ total symptom score improved by 6.6 points with TNX-103 and 6.5 points with placebo, producing a treatment difference of only 0.1 points.
Those overall results put greater emphasis on prespecified subgroup findings. Among 119 patients whose baseline 6-minute walk distance was below the trial median of 333 meters, TNX-103 produced a 26.3-meter placebo-adjusted improvement, with a nominal p-value of 0.0112.
Patients aged 71 or older showed a 27.1-meter treatment difference, while the oldest tertile, above 74 years, showed a 37.6-meter difference. These analyses suggest treatment effects may have been concentrated among patients with greater disease burden, but they do not change the trial’s primary endpoint failure.
Why This Matters for Investors
The Phase 3 primary endpoint miss represents a material setback for TNX-103’s existing development pathway. Rather than proceeding on the basis of a successful pivotal study, Tenax now intends to discuss a revised strategy with regulators centred on identifying patients more likely to respond.
Supporting biological findings could become important to that discussion. Across the overall population, TNX-103 reduced NT-proBNP by 49% relative to placebo, with a nominal p-value below 0.0001. Right ventricular systolic pressure was reduced by 3.5 mmHg versus placebo, with a nominal p-value of 0.0045.
However, Tenax explicitly cautioned that the nominal p-values were not adjusted for multiplicity and that the biomarker, hemodynamic and subgroup analyses do not establish efficacy. The 6-minute walk quartile analysis showing progressively weaker effects among patients with greater baseline exercise capacity was also post hoc.
Safety provides a more supportive component of the dataset. Serious adverse events were similar at 10.8% for TNX-103 and 10.7% for placebo, and the company reported no new safety signals. Overall and treatment-related adverse events were nevertheless more frequent with TNX-103 than placebo.
For investors, the central issue therefore shifts from whether LEVEL succeeded to whether the subgroup findings can support a viable new registrational pathway.
What to Watch Next
Tenax plans to request a Type C meeting with the FDA to discuss the complete LEVEL dataset and an enrichment strategy focused on patients with greater disease burden. The company also intends to seek scientific consultation from the European Medicines Agency.
The regulatory discussions are particularly important because Tenax said the FDA had previously agreed that a single Phase 3 study achieving a p-value of 0.01 could be sufficient for an NDA submission in PH-HFpEF. How that prior agreement applies following LEVEL’s primary endpoint failure will be a key question for the development programme.
Investors will also get a more detailed look at the LEVEL results when they are presented in a Late-Breaking Clinical Science session at the ESC Congress 2026, scheduled for August 28-31 in Munich.