Tenax Therapeutics’ stock dropped by nearly 90% after a Phase III trial of its oral therapy for pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) failed to meet its endpoints.
Tenax saw its stock drop from $13.44 at market close on 7 August to $1.38 at market close on 10 August – an 89.73% drop, following the trial failure announcement.
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The LEVEL trial (NCT05983250), which investigated TNX-103, an oral formulation of levosimendan, did not meet its primary endpoint of improvement in the six-minute walk distance (6MWD) compared to placebo. After 12 weeks, in the treatment cohort, the least-squares mean was 14 metres, while it was 10.4 metres in those treated with placebo, making a least-squares mean difference of 3.5 metres.
The trial also failed to show benefit on the key secondary endpoint of improvement in Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) after 12 weeks. In the TNX-103 cohort, there was a least-squares mean score of 6.6 compared to 6.5 on placebo, with a least-squares mean difference of just 0.1 point.
Regarding biomarker measurements, Natriuretic Peptide Tests (NT-proBNP) in the overall population achieved a geometric least-squares mean ratio of 0.51 versus placebo, corresponding to a 49% reduction.
Tenax did suggest that prespecified analysis identified a substantial beneficial treatment effect in patients with greater disease burden. In patients whose baseline 6MWD was below the trial median, there was a least-squares mean treatment improvement of 26.7 metres in those treated with TNX-103, while patients on placebo declined 2.6 metres.
TNX-103 was generally safe and well tolerated, with serious adverse events and adjudicated clinical worsening events balanced across treatment arms.
Dr Sanjiv Shah, director of the HFpEF Program at Northwestern University Feinberg School of Medicine and LEVEL’s principal investigator, said: “Although the result in the overall population was not statistically significant, the LEVEL trial is an important advancement for patients with PH-HFpEF, a disease that still has no approved therapy. What stands out to me is the marked reduction in NT-proBNP, the most established marker of cardiac wall stress and prognosis in heart failure, which was reduced by an extraordinary 49% relative to placebo.
“In my opinion, a drug that lowers wall stress and modifies cardiac structure and function this robustly is likely to be disease-modifying. The improvement in exercise capacity was concentrated in patients with lower baseline walk distance and more advanced disease, which is consistent with a therapy that may improve long-term outcomes in those patients who need it most,” Shah added.
Intravenous levosimendan, which is marketed by the Orion Corporation as Simdax, is a well-established treatment for patients with advanced heart failure, but it was never approved in the US. Alongside oral levosimendan, Tenax is also developing an intravenous version with hopes to break into the US PH-HFpEF market, which has no approved therapies.
Orion Corporation and Tenax Therapeutics entered into a licensing and supply partnership for the development of oral levosimendan in 2020. This followed their first partnership to develop levosimendan in 2013.
Based on the data from the prespecified cohort of the LEVEL trial, Tenax has requested a Type C meeting with the US Food and Drug Administration (FDA) while, in parallel, seeking scientific consultation from the European Medicines Agency (EMA).
Full results from LEVEL will be presented in a Late-Breaking Clinical Science session at the European Society of Cardiology (ESC) Congress 2026, being held 28-31 August in Munich, Germany.
