Tenax Therapeutics Expands Phase 3 LEVEL Program, Advancing Two TNX-103 (Oral Levosimendan) Registrational Studies for the Treatment of PH-HFpEF
Tenax Therapeutics (NASDAQ: TENX) has announced significant expansions to its Phase 3 LEVEL program for TNX-103 (oral levosimendan) in treating PH-HFpEF. The FDA has approved two key developments:
1. An amendment to expand the ongoing LEVEL study from 152 to 230 patients, increasing statistical power to over 95%. The study is expected to complete enrollment by end of 2025 with topline data expected mid-2026.
2. Approval to initiate LEVEL-2, a second global Phase 3 study, starting in 2025.
Current blinded LEVEL data shows strong patient retention with >95% continuation rates across multiple metrics. The company's $100 million financing from August 2024 supports these expanded trials. The studies aim to provide sufficient data for regulatory submissions in the U.S. and other regions for TNX-103, which targets PH-HFpEF, a condition currently without approved treatments.
Tenax Therapeutics (NASDAQ: TENX) ha annunciato importanti espansioni al suo programma di Fase 3 LEVEL per TNX-103 (levosimendano orale) nel trattamento della PH-HFpEF. La FDA ha approvato due sviluppi chiave:
1. Un emendamento per espandere lo studio LEVEL in corso da 152 a 230 pazienti, aumentando la potenza statistica a oltre il 95%. Si prevede che lo studio completi l'arruolamento entro la fine del 2025, con dati preliminari attesi per metà 2026.
2. Approvazione per avviare LEVEL-2, un secondo studio globale di Fase 3, che inizierà nel 2025.
I dati attuali dello studio LEVEL, in fase di cecità, mostrano una forte retention dei pazienti con tassi di continuazione superiori al 95% su più metriche. Il finanziamento di 100 milioni di dollari dell'azienda da agosto 2024 supporta questi studi espansi. Gli studi mirano a fornire dati sufficienti per le sottomissioni regolatorie negli Stati Uniti e in altre regioni per TNX-103, che mira alla PH-HFpEF, una condizione attualmente priva di trattamenti approvati.
Tenax Therapeutics (NASDAQ: TENX) ha anunciado expansiones significativas a su programa de Fase 3 LEVEL para TNX-103 (levosimendano oral) en el tratamiento de PH-HFpEF. La FDA ha aprobado dos desarrollos clave:
1. Una enmienda para expandir el estudio LEVEL en curso de 152 a 230 pacientes, aumentando el poder estadístico a más del 95%. Se espera que el estudio complete la inscripción a finales de 2025, con datos preliminares esperados a mediados de 2026.
2. Aprobación para iniciar LEVEL-2, un segundo estudio global de Fase 3, que comenzará en 2025.
Los datos actuales del estudio LEVEL, que se mantienen en ciego, muestran una fuerte retención de pacientes con tasas de continuación superiores al 95% en múltiples métricas. El financiamiento de 100 millones de dólares de la empresa en agosto de 2024 apoya estos ensayos ampliados. Los estudios tienen como objetivo proporcionar datos suficientes para las presentaciones regulatorias en EE. UU. y otras regiones para TNX-103, que se dirige a la PH-HFpEF, una condición actualmente sin tratamientos aprobados.
테낙스 테라퓨틱스 (NASDAQ: TENX)는 PH-HFpEF 치료를 위한 TNX-103 (경구용 레보시멘단) 임상 3상 LEVEL 프로그램의 중요한 확장을 발표했습니다. FDA는 두 가지 주요 개발을 승인했습니다:
1. 현재 진행 중인 LEVEL 연구의 환자 수를 152명에서 230명으로 확대하는 수정안으로, 통계적 힘을 95% 이상으로 증가시킵니다. 연구는 2025년 말까지 등록을 완료할 것으로 예상되며, 주요 데이터는 2026년 중반에 예상됩니다.
2. 2025년에 시작되는 두 번째 글로벌 3상 연구인 LEVEL-2를 시작할 수 있도록 승인되었습니다.
현재 블라인드 LEVEL 데이터는 여러 지표에서 95% 이상의 지속적인 환자 유지율을 보여줍니다. 2024년 8월에 회사가 확보한 1억 달러의 자금은 이러한 확장된 시험을 지원합니다. 이 연구들은 TNX-103에 대한 미국 및 기타 지역의 규제 제출을 위한 충분한 데이터를 제공하는 것을 목표로 하며, 이는 현재 승인된 치료법이 없는 PH-HFpEF를 겨냥하고 있습니다.
Tenax Therapeutics (NASDAQ: TENX) a annoncé d'importantes extensions de son programme de Phase 3 LEVEL pour TNX-103 (levosimendan oral) dans le traitement de la PH-HFpEF. La FDA a approuvé deux développements clés :
1. Un amendement pour élargir l'étude LEVEL en cours de 152 à 230 patients, augmentant la puissance statistique à plus de 95 %. L'étude devrait compléter le recrutement d'ici fin 2025, avec des données préliminaires attendues pour mi-2026.
2. Approbation pour initier LEVEL-2, une deuxième étude mondiale de Phase 3, qui commencera en 2025.
Les données actuelles de l'étude LEVEL, en aveugle, montrent une forte rétention des patients avec des taux de continuation supérieurs à 95 % sur plusieurs critères. Le financement de 100 millions de dollars de l'entreprise d'août 2024 soutient ces essais élargis. Les études visent à fournir des données suffisantes pour les soumissions réglementaires aux États-Unis et dans d'autres régions pour TNX-103, qui cible la PH-HFpEF, une condition actuellement sans traitements approuvés.
Tenax Therapeutics (NASDAQ: TENX) hat bedeutende Erweiterungen seines Phase-3-LEVEL-Programms für TNX-103 (orales Levosimendan) zur Behandlung von PH-HFpEF angekündigt. Die FDA hat zwei wesentliche Entwicklungen genehmigt:
1. Eine Änderung zur Erweiterung der laufenden LEVEL-Studie von 152 auf 230 Patienten, wodurch die statistische Power auf über 95% erhöht wird. Es wird erwartet, dass die Studie bis Ende 2025 die Rekrutierung abschließt, wobei die wichtigsten Daten Mitte 2026 erwartet werden.
2. Genehmigung zur Einleitung von LEVEL-2, einer zweiten globalen Phase-3-Studie, die 2025 beginnt.
Die aktuellen verblindeten LEVEL-Daten zeigen eine starke Patientenbindung mit über 95% Fortsetzungsraten über mehrere Metriken hinweg. Die 100 Millionen Dollar Finanzierung des Unternehmens aus August 2024 unterstützt diese erweiterten Studien. Die Studien zielen darauf ab, ausreichende Daten für regulatorische Einreichungen in den USA und anderen Regionen für TNX-103 bereitzustellen, das auf PH-HFpEF abzielt, eine Erkrankung, für die derzeit keine zugelassenen Behandlungen existieren.
- $100M financing secured in August 2024
- FDA approval for expanded Phase 3 program
- >95% patient retention rates in current trial
- Funded beyond projected topline data release
- No approved treatment yet for PH-HFpEF
- Extended timeline to complete enrollment (end of 2025)
- Final data not available until mid-2026
Insights
Tenax Therapeutics' announcement represents a significant expansion of its Phase 3 program for TNX-103 (oral levosimendan) in PH-HFpEF. The expansion includes increasing LEVEL study enrollment from 152 to 230 patients, boosting statistical power to over 95%, and initiating a second global Phase 3 trial (LEVEL-2).
The company's $100 million financing from August 2024 provides important runway beyond the projected mid-2026 topline data readout for LEVEL. This expanded clinical program demonstrates management's confidence in their candidate while simultaneously accelerating the path to potential market authorization.
The blinded interim safety data showing >95% continuation rates across multiple measures is particularly encouraging, indicating good tolerability in this patient population. If approved, TNX-103 would enter a market with no approved therapies for PH-HFpEF, potentially positioning Tenax to capture significant market share.
This parallel-path strategy with two registrational trials could expedite regulatory submissions in multiple markets, though investors should note that full enrollment isn't expected until year-end 2025, with pivotal data in mid-2026. Despite the significant runway provided by recent financing, Tenax remains a pre-revenue, development-stage company with all the associated risks of clinical-stage biopharmaceuticals focused on a single program.
The expansion of Tenax's Phase 3 program for oral levosimendan in PH-HFpEF addresses a critical unmet need in cardiopulmonary medicine. PH-HFpEF (Pulmonary Hypertension with Heart Failure with preserved Ejection Fraction) represents a challenging condition with treatment options and poor prognosis.
From a clinical perspective, the increased statistical powering to over 95% significantly strengthens the trial design, reducing the risk of false negatives. The preliminary blinded safety data showing >95% patient retention is particularly noteworthy in this difficult-to-treat population. The high continuation rates in both the initial treatment phase and open-label extension suggest favorable tolerability, especially impressive for a medication administered three times daily.
The planned year-long treatment duration in LEVEL-2 will provide important longer-term safety data beyond the initial efficacy signals. The 6-minute walk distance (6MWD) primary endpoint at 26 weeks is clinically meaningful and directly correlates with functional capacity and quality of life in these patients.
If successful, oral levosimendan could become the first approved therapy specifically for PH-HFpEF, potentially transforming the standard of care. The parallel conduct of two registrational trials acknowledges the high regulatory bar for novel cardiovascular therapies while potentially accelerating the path to approval, assuming positive results from both studies.
Amendment to Enlarge Phase 3 LEVEL Study, Increasing Statistical Powering, Accepted by FDA, Expected to be Fully Enrolled Around Year End 2025
Agreement by FDA to Initiate Second Global Phase 3 Study, LEVEL-2, with First Patient Expected to be Enrolled this Year
CHAPEL HILL, N.C., March 05, 2025 (GLOBE NEWSWIRE) -- Tenax Therapeutics, Inc. (Nasdaq: TENX) (“Tenax Therapeutics” or the “Company”), a Phase 3, development-stage pharmaceutical company using clinical insights to develop novel cardiopulmonary therapies, today announced the U.S. Food and Drug Administration (FDA) has completed their review of Tenax Therapeutics’ updated Phase 3 development plan for TNX-103 (oral levosimendan), including an Amendment to expand enrolment and increase the power of the ongoing Phase 3 LEVEL study, and the protocol for LEVEL-2, Tenax Therapeutics’ second registrational Phase 3 study. The Company today announced it expects to enroll 230 patients in the LEVEL study, increasing the statistical powering of the study to over
“We are increasing our investment in the clinical development plan for TNX-103 by expanding the ongoing LEVEL study and accelerating our plans to initiate the second registrational study, LEVEL-2. With the momentum provided from our
LEVEL Study Expansion Enhances Statistical Power
The LEVEL study, evaluating TNX-103 for the treatment of PH-HFpEF, will expand enrollment from 152 to at least 230 patients, increasing the statistical powering of the study. The Company is on track to enroll the first 150 subjects in the first half of 2025, expects to complete enrollment by around the end of 2025, and expects to present topline data from the LEVEL study in the middle of 2026.
As of late February 2025, blinded LEVEL data reveal TNX-103 to be well-tolerated in patients with PH-HFpEF:
- >
95% of patients who randomized have remained on therapy; - >
95% of patients who completed 12 weeks have elected to enter the OLE; and - >
95% of patients who entered the OLE have continued participation to this point.
Tenax Therapeutics’ Chief Medical Officer, Stuart Rich, MD, summarized: “In addition to high rates of study and therapy continuation, the adherence to the TID regimen has been high, and no new safety signals have been detected. About half the patients in the OLE have been on study for over 6 months, a few of them for more than a year, with very reassuring participation levels observed during the OLE.”
LEVEL-2: A Global Registrational Trial
Additionally, Tenax Therapeutics received input from the FDA on the protocol for the LEVEL-2 study, and expects this second, global registrational clinical trial to evaluate levosimendan in patients with PH-HFpEF to start enrolling this year, in several countries. The primary endpoint of 6MWD will be assessed at 26 weeks. Tenax intends to enroll a larger sample than LEVEL and evaluate patients for a full year of double-blind, placebo-controlled therapy, providing FDA and European reviewers a robust safety database for their benefit/risk assessments.
“TNX-103 has the potential to meaningfully improve the quality of life of patients with PH-HFpEF, an underdiagnosed disease with significant unmet needs and no currently approved treatment options. I remain very hopeful that with positive Phase 3 results, these patients will finally have an approved treatment available,” said Dr. Rich. “We are continuing to work closely with the FDA, and are grateful for their input, which enables Tenax to accelerate development timelines of a potential first therapy for this devastating form of PH.”
About the Phase 3 LEVEL Study ( NCT05983250 )
The LEVEL Study is a Phase 3, double-blind, randomized, placebo-controlled study of oral levosimendan in patients with PH-HFpEF. Approximately 230 subjects will be randomized in a 1:1 ratio to receive an oral dose of levosimendan (2 mg/day) or placebo for Weeks 1 to 4 and 3 mg/day or placebo for Weeks 5 to 12. The primary outcome measure for the study is change in six-minute walk distance from Baseline to Week 12. All randomized subjects will have the option to enter the 92-week OLE following the completion of all study endpoints at Week 12.
About the Phase 3 LEVEL-2 Study
LEVEL-2 is a global Phase 3, double-blind, randomized, placebo-controlled study of oral levosimendan in patients with PH-HFpEF. Patients will be randomized to receive an oral dose of levosimendan (2mg/day) or placebo for Weeks 1 to 4 and 3mg/day or placebo from Week 5 onward. The primary endpoint of 6MWD will be assessed at 26 weeks.
About Levosimendan (TNX-101, TNX-102, TNX-103)
Levosimendan is a unique, potassium ATP channel activator and calcium sensitizer that affects the heart and vascular system through multiple mechanisms of action, and that is being developed as an oral therapy (TNX-103) for pulmonary hypertension (PH) with heart failure with preserved ejection fraction (PH-HFpEF). Initially discovered and developed by Orion Corporation in Finland, intravenous levosimendan has been granted market authorization in 60 countries outside the United States for use in hospitalized patients with acutely decompensated heart failure. Results of Tenax Therapeutics’ Phase 2 HELP study of levosimendan in patients with HFpEF demonstrated that IV levosimendan (TNX-101) produces potent dilation of the central and pulmonary venous circulations which translates into an improvement in exercise capacity, a discovery that is the basis of LEVEL, the Phase 3 investigation of Tenax Therapeutics’ potential groundbreaking therapy. To date, no other drug therapy has demonstrated improved exercise tolerance in patients with PH associated with HFpEF, “a growing epidemic with high morbidity and mortality and no treatment. The clear unmet need and lethal nature of PH-HFpEF must be met with novel solutions at all levels of therapeutic development” (AHA Scientific Advisory, “A Call to Action,” 2022).
About Tenax Therapeutics
Tenax Therapeutics, Inc. is a Phase 3, development-stage pharmaceutical company using clinical insights to develop novel cardiopulmonary therapies. The Company owns global rights to develop and commercialize levosimendan, which it has prioritized. Tenax Therapeutics also may resume developing its unique oral formulation of imatinib. For more information, visit www.tenaxthera.com. Tenax Therapeutics’ common stock is listed on The Nasdaq Stock Market LLC under the symbol “TENX”.
Caution Regarding Forward-Looking Statements
Except for historical information, all of the statements, expectations and assumptions contained in this press release are forward-looking statements. These forward-looking statements may include information concerning possible or projected future business operations. Actual results might differ materially from those explicit or implicit in the forward-looking statements. Important factors that could cause actual results to differ materially include: risks of our clinical trials, including, but not limited to, the timing, delays, costs, design, initiation, enrollment, and results of such trials; any delays in regulatory review and approval of product candidates in development; risks related to our business strategy, including the prioritization and development of product candidates; reliance on third parties, including Orion Corporation, our manufacturers and CROs; risks regarding the formulation, production, marketing, customer acceptance and clinical utility of our product candidates; our estimates regarding the potential market opportunity for our product candidates; the potential advantages of our product candidates; risks associated with our cash needs; our ability to maintain our culture and recruit, integrate and retain qualified personnel and advisors, including on our Board of Directors; our competitive position; intellectual property risks; volatility and uncertainty in the global economy and financial markets in light of the possibility of pandemics, global financial and geopolitical uncertainties, including in the Middle East and the Russian invasion of and war against the country of Ukraine; changes in legal, regulatory and legislative environments in the markets in which we operate and the impact of these changes on our ability to obtain regulatory approval for our products; and other risks and uncertainties set forth from time to time in our SEC filings. Tenax Therapeutics assumes no obligation and does not intend to update these forward-looking statements except as required by law.
Contact:
Investor and Media:
Merrill Barrett
Argot Partners
tenax@argotpartners.com
FAQ
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