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Nearly three decades after its failed bid for FDA approval, the cardiovascular drug levosimendan is still struggling to secure a decisive clinical win to enter the U.S. market. In the latest chapter of the drug’s U.S. odyssey, Tenax Therapeutics reported that an oral version of levosimendan missed the primary endpoint of a phase 3 trial, leaving the biotech to rely on subgroup data to chart a narrow path forward with the FDA. In the phase 3 Level trial, Tenax’s oral levosimendan, coded TNX-103, failed to outperform placebo in improving 6-minute walk distance in patients with pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF), the company said Monday. The least-squares mean difference between the levosimendan group and the control arm was merely 3.5 meters, with a p-value of 0.63. The key secondary endpoint, improvement in Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS), also returned negative, with a least-squares mean difference of 0.1 points. Despite the flop, Tenax has zeroed in on a prespecified subgroup of patients with greater disease burden and plans to request a meeting with the FDA to discuss a path forward for TNX-103. Specifically, among 119 patients who walked less than the trial median of 333 meters (about 1,093 feet) at baseline, levosimendan demonstrated an improvement of 26.3 meters versus placebo on the 6-minute walk test, with a nominal p-value of 0.0112. On average, patients on Tenax's drug improved by 26.7 meters, while those on placebo declined by 2.6 meters. In an Aug. 10 statement, Tenax’s chief medical officer, Stuart Rich, M.D., called this finding “a strong result in a more characteristic HFpEF population that needs this therapy.” The increase in walking distance was accompanied by a 49% decrease in a heart failure protein biomarker, NT-proBNP, and a reduction in right ventricular systolic pressure by 3.5 mmHg, compared to placebo. According to the Level trial’s principal investigator, Sanjiv Shah, M.D., from Northwestern University, the 49% NT-proBNP reduction versus placebo is larger than any prior HFpEF trial. “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,” Rich said. “In my opinion, a drug that lowers wall stress and modifies cardiac structure and function this robustly is likely to be disease-modifying,” Shah said. “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.” Originally developed by Orion Pharma, levosimendan got its initial European approval in 2000 under the brand name Simdax, an intravenous infusion for treating acutely decompensated chronic heart failure. But the drug has a difficult clinical and regulatory past in the U.S. In 1999, Orion withdrew its application with the FDA after the agency requested larger phase 3 outcome trials to support levosimendan’s case. Later, the phase 3 Revive II trial of 600 patients showed some short-term symptomatic improvement with the inodilator on top of standard therapy, but more deaths were recorded in the levosimendan arm at 90 days, along with higher rates of certain adverse events, such as hypotension, raising safety concerns. In 2007, Abbott terminated its U.S. development efforts for the drug after the large-scale Survive trial of more than 1,300 patients, which compared levosimendan with dobutamine, failed to meet its primary endpoint of a statistically significant reduction in 180-day all-cause mortality. At the time, Abbott concluded that conducting additional phase 3 studies would not be commercially reasonable. U.S. rights to levosimendan then landed at Tenax. But in 2017, the drug again failed in the phase 3 Levo-CTS trial in patients with left ventricular dysfunction undergoing cardiac surgery. Prophylactic levosimendan did not result in any significant improvement versus placebo on a composite endpoint of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device. Tenax licensed North American rights to oral levosimendan from Orion in 2020, then expanded the deal in 2024 to cover oral and subcutaneous levosimendan globally for PH-HFpEF. Compared with the original intravenous version, a daily oral formulation could offer “an advantage of stable dosing and eliminate the risk of line infections and thrombosis,” a team of researchers, including Shah, wrote in 2023.

DALLAS, TX, UNITED STATES, January 15, 2026 / EINPresswire.com / -- Mark Cuban Cost Plus Drug Company (Cost Plus Drugs) and Alchem Laboratories Corporation (Alchem) today announced the formation of a strategic alliance to develop essential medicine therapeutics, improving supply chain resiliency. Cost Plus Drugs is employing a highly automated and flexible manufacturing platform that integrates AI and machine learning for real-time quality assessment and process optimization to produce lidocaine, a widely used anesthetic, and diltiazem, a calcium channel blocker used to treat heart conditions., Alchem provided process development of these APIs for Cost Plus Drugs. Alchem has experience performing process development, scale-up, and GMP manufacturing of over 200 APIs, including the USP APIs amikacin, atropine, carboplatin, ciprofloxacin, cisplatin, dantrolene, dobutamine, dopamine, fluconazole, levofloxacin, linezolid, metronidazole, phentolamine, sulfamethoxazole, trimethoprim, and verteporfin. Under the terms of the agreement, the parties will also collaborate to supply 86 essential medicines and medical countermeasures including critical care drugs and antimicrobials. In September 2025, Alchem Laboratories and Applied Pharmaceutical Innovation (API-Canada) announced a Strategic Alliance to advance Antimicrobial and Essential Medicines Programs. This new alliance expands work under that collaboration, providing enhanced and equitable access to antimicrobial agents and essential medicines, with North American onshoring of critical therapies to support public needs. Alchem and API-Canada will initially work on lidocaine and diltiazem vial supply for Canada, as well as antimicrobials and vial manufacturing. As part of the arrangement, API-Canada will also support diltiazem and lidocaine vial supply more broadly as required by the collaborators. Both Alchem and Cost Plus Drugs maintain the flexibility to pursue funding and development pathways commensurate with project maturity and strategic alignment. About Mark Cuban Cost Plus Drugs The Mark Cuban Cost Plus Drug Company, PBC (Cost Plus Drugs) aims to fundamentally change the way the pharmaceutical industry operates. As a public-benefit corporation, its social mission of improving public health is just as important as the bottom line. Cost Plus Drugs transparently charges a standard markup on every drug it sells. The costplusdrugs.com online pharmacy launched in January 2022 now carries over 2,300 prescription products, delivered by mail to thousands of happy customers every day. Customers can also go to participating retail pharmacies to receive Cost Plus Drugs pricing through the Team Cuban Card. Cost Plus Drugs is working with health plans, managed-care organizations, PBMs, and self-insured employers to bring these same savings to benefit plans nationwide. Learn more at www.markcubancostplusdrugcompany.com . Dr. Alex Oshmyansky, CEO Mark Cuban Cost Plus Drugs press@costplusdrugs.com About Alchem Laboratories Corporation Alchem Laboratories Corporation is a pharmaceutical development company dedicated to advancing therapies in areas of high unmet medical need, with an emphasis on accessible, high-quality essential medicines. Alchem is a subsidiary of TRON Group Inc. (OTC:TGRP). Dr. James D Talton, CEO Alchem Laboratories Corporation info@alchem.com About Applied Pharmaceutical Innovation Applied Pharmaceutical Innovation is one of Canada’s largest not-for-profit life sciences commercialization organizations. Headquartered in Edmonton, Alberta, Applied Pharmaceutical Innovation works to accelerate the development, manufacturing, and commercialization of life sciences products, and is home to Canada’s largest security of supply initiative. Jenna Bienert Applied Pharmaceutical Innovation communications@appliedpharma.ca Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.