Tenax Therapeutics, Inc. announces the presentation of positive data from a study of PH-HFpEF patients being treated with oral levosimendan. The data, collected during the transition from intravenous (IV) to oral levosimendan in the open-label extension (OLE) of the HELP (Hemodynamic Evaluation of Levosimendan in PH-HFpEF) trial, were presented at the Heart Failure Society of America (HFSA) Scientific Sessions 2022, held from October 1 –3, 2022. This substudy of 18 PH-HFpEF patients who transitioned from IV to oral levosimendan, included an evaluation of safety and efficacy across several measures.

As compared with the patient's baseline (on IV levosimendan), the mean change in resting heart rate was 4.9 (SD 7.5) beats/min, the mean systolic arterial blood pressure was 4.1 (SD 12.6) mm Hg, the mean change in 6-minute walk distance (6MWD) (n=17) was 13.1 (SD 39.5) meters, BNP (n=8) was -133.3 (SD 136.6) pg/dl, and NT-proBNP (n=7) was -239.4 (SD 548.1) pg/dl. The mean Kansas City Cardiomyopathy Questionnaire scores (KCCQ-TS, KCCQ-CS and KCCQ-OS) (n=16) improved by 4.7, 2.5 points and 3.7 points, respectively. The authors concluded that the levosimendan oral formulation was well tolerated without safety concerns over a 6-8-week period in patients with PH-HFpEF who received IV levosimendan for an average of 18 months.

There were no serious adverse events (SAEs) related to oral levosimendan therapy. Oral levosimendan was associated with further numerical improvements in 6MWD, BNP/NT-ProBNP, and all key KCCQ domains (encompassing physical symptoms, functional limitation, quality of life, and social function), suggesting oral levosimendan at 3-4 mg/day may provide a superior formulation for chronic use in PH-HFpEF patients when compared to the intravenous administration of levosimendan. The Phase 2 HELP Study of levosimendan, initiated in 2019, enrolled patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF) and was the first clinical trial to show an improvement in exercise capacity in this group of patients with WHO Group 2 pulmonary hypertension (PH associated with left heart disease).

Patients who completed HELP and enrolled in the open-label extension study were offered the opportunity to transition from weekly IV infusions to daily oral tablets. The IV-to-oral transition substudy tested the hypothesis that stable dosing – a daily oral formulation rather than a weekly IV infusion – would not only eliminate the risk of IV-related line infections and thrombosis, but would safely retain the observed efficacy of IV levosimendan. Levosimendan is a unique potassium ATP channel activator and calcium sensitizer that affects the heart and vascular system through multiple mechanisms of action.

Initially discovered and developed by Orion Corporation in Finland, intravenous levosimendan is approved in over 60 countries outside the United States for use in hospitalized patients with acutely decompensated heart failure. Tenax Therapeutics has North American rights to develop and commercialize oral (TNX-103) and subcutaneous (TNX-102) formulations of levosimendan. Results of Tenax Therapeutics' Phase 2 trial of levosimendan in patients with pulmonary hypertension (PH) and heart failure with preserved ejection fraction (HFpEF) demonstrated that IV levosimendan produces potent dilation of the central and pulmonary venous circulations which translates into an improvement in exercise capacity, a discovery that forms the basis for the Phase 3 investigation of Tenax Therapeutics' potential therapy.

To date, no other drug therapy has improved exercise tolerance in patients with PH associated with HFpEF, recently referred to as the greatest unmet need in cardiovascular disease.