Tenax Therapeutics presents Phase 3 LEVEL data at ESC 2026
Tenax Therapeutics has presented additional Phase 3 data from its LEVEL trial of TNX-103, an oral formulation of levosimendan, at the European Society of Cardiology Congress 2026 in Munich. The results, delivered in a late-breaking clinical science session, concentrated on a prespecified subgroup of patients with the lowest baseline exercise capacity and produced statistically significant improvements across several measures of cardiac stress and pulmonary pressure.
The LEVEL trial enrolled 241 patients with pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF) across 41 sites in the United States and Canada. In the overall population, the primary endpoint, change in six-minute walk distance (6MWD) at week 12, did not reach statistical significance. Neither did the key secondary endpoint measuring symptom burden via the Kansas City Cardiomyopathy Questionnaire. Those headline misses were reported at topline earlier this year.
Subgroup findings and biomarker signals
Among patients whose baseline 6MWD fell below the trial median of 333 metres, roughly half the cohort at 119 patients, the picture was more favourable. TNX-103 produced a least-squares mean treatment difference of 26.3 metres in walk distance compared with placebo (p = 0.0112). In the same group, NT-proBNP, a biomarker of cardiac wall stress, fell by 47% relative to placebo (p less than 0.0001), and right ventricular systolic pressure was reduced by 4.9 mmHg (p = 0.009). The NT-proBNP and RVSP analyses were conducted post-hoc.
Sanjiv Shah, Director of the HFpEF Program at Northwestern University Feinberg School of Medicine and LEVEL's principal investigator, said the data pointed toward a potential therapeutic benefit in PH-HFpEF patients largely independent of effects on walk distance: "Even patients who did not show a significant improvement in exercise capacity had the same magnitude of reduction in cardiac wall stress and pulmonary artery pressures, changes that correspond to a reduction in heart failure hospitalizations over longer follow-up."
Tenax's chief medical officer, Stuart Rich, said the company now has a clear strategy for LEVEL-2, its follow-on Phase 3 trial, which will enrich for patients whose baseline 6MWD aligns with the lower-function subgroup that drove the treatment effect in LEVEL.
Competitive landscape and regulatory path
PH-HFpEF remains a largely untreated condition. No therapy has received regulatory approval specifically for the indication. The recent CADENCE trial of sotatercept, a TGF-beta superfamily inhibitor developed by MSD, enrolled patients with baseline walk distances of 274 to 285 metres, closer to the subgroup that appeared to respond to TNX-103 in LEVEL than to the trial's overall median. This comparison, cited in the ESC presentation, suggests that patient selection may have been a material factor in the broader trial's primary miss and supports the rationale for enriching LEVEL-2.
Levosimendan already holds market authorisation in 60 countries as an intravenous agent for acute decompensated heart failure, though it is not approved in the United States or Canada. Tenax holds global rights to develop and commercialise both IV and oral forms for PH-HFpEF. The company has indicated it will move quickly toward LEVEL-2, consistent with longstanding FDA guidance on population enrichment strategies for adaptive programme design.
The FDA has previously accepted subgroup-driven enrichment in heart failure programmes, though any such design will require agency alignment before enrolment begins. Investors will look for the LEVEL-2 protocol, a timeline to study start, and an updated cash-runway disclosure as the next material milestones for the Chapel Hill, North Carolina-based company.